Clinician Reviews

TOPLINE:

Among patients with colorectal cancer (CRC), those with complicated diabetes were at higher risk of poor survival than their peers without diabetes, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.

METHODOLOGY:

• This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
• The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
• The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
•  

TAKEAWAY:

• Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
• Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
• Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
• Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.

IN PRACTICE:

“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.

SOURCE:

The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.

LIMITATIONS:

Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.

DISCLOSURES:

Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Among patients with colorectal cancer (CRC), those with complicated diabetes were at higher risk of poor survival than their peers without diabetes, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.

METHODOLOGY:

• This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
• The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
• The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
•  

TAKEAWAY:

• Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
• Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
• Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
• Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.

IN PRACTICE:

“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.

SOURCE:

The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.

LIMITATIONS:

Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.

DISCLOSURES:

Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

TOPLINE:

Among patients with colorectal cancer (CRC), those with complicated diabetes were at higher risk of poor survival than their peers without diabetes, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.

METHODOLOGY:

• This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
• The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
• The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
•  

TAKEAWAY:

• Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
• Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
• Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
• Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.

IN PRACTICE:

“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.

SOURCE:

The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.

LIMITATIONS:

Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.

DISCLOSURES:

Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A recent survey found that less than half of pharmacies in the Washington area had a 30-day supply of either 2.5-mg or 10-mg tablets of oral minoxidil, used for both hair loss and hypertension.

Patients are not finding out until they go to pick up their prescription, which can result in an interruption of treatment – and, potentially a loss of hard-earned hair gain, said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was the lead author of the survey, published online on Oct. 26 as a research letter in the Journal of Drugs in Dermatology.

Going off low-dose oral minoxidil may spark a telogen effluvium event, and that is very disappointing to patients, Dr. Friedman told this news organization.

“There needs to be some system that alerts us,” he said. “Even if it’s a minor shortage, just so we’re aware. We can then prepare patients,” he added, noting that it would be better for someone to be taking a lower-than-normal dose rather than no medication at all while they wait for a refill.

Minoxidil has long been approved in a topical formulation to treat androgenetic alopecia, but a low-dose oral form has gained currency in the wake of findings that it might more effectively treat hair loss, and is without side effects. A New York Times article in August 2022 touting low-dose oral minoxidil as a cheap and effective hair loss drug appeared to ignite interest in this option. In May, 2023, researchers reporting in JAMA Network Open demonstrated a significant uptick in prescriptions for oral minoxidil in the wake of the article’s publication.

Oral minoxidil is approved by the Food and Drug Administration only for hypertension, but dermatologists are prescribing it off-label at a lower dose for hair loss. Dr. Friedman said it’s not clear whether the shortages his team found are national in scope, or whether they are a result of increased demand, or other factors.

After several patients told him they were having trouble filling minoxidil prescriptions, and colleagues said they’d had patients with similar experiences, Dr. Friedman and his colleagues undertook the survey. In the first week of October 2023, they contacted 277 pharmacies by phone in Washington and surrounding Virginia and Maryland counties. The pharmacies were CVS, Giant, Walgreens, and Harris Teeter.

Of the 277 pharmacies they contacted, 40% (111) reported availability of 2.5-mg tablets for a 30-day supply, and just under 30% (82) reported having 10-mg tablets for a 30-day supply.

For treating hair loss, most patients are prescribed 2.5-mg pills, with starting doses ranging from 0.625 mg to 5 mg twice a day, Dr. Friedman said. The 10-mg dose is more frequently prescribed for hypertension.

Only 28% (19 of 67) of the Maryland pharmacies had 30-day supplies of 2.5-mg tablets on hand, and just 22% (15) of the Maryland pharmacies had 30-day supplies of 10-mg tablets. In Northern Virginia, 44% (63 of 143) of the pharmacies had 30-day supplies of the 2.5 mg tablets, as did just 43% (29 of 67) of the Washington pharmacies.

Dr. Friedman said he has started giving patients paper prescriptions they can use to shop around, rather than electronically sending a prescription to a particular pharmacy.

Neither the Food and Drug Administration nor the American Society of Health System Pharmacists lists oral minoxidil as a drug in shortage.

Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, said the organization received a report from wholesalers in mid-September showing spotty oral minoxidil availability, with the drug on backorder with some manufacturers.  ASHP's shortages list is compiled from reports from physicians, manufacturers and wholesalers, he said.

Under what he calls "blue sky conditions," pharmacies using a just-in-time inventory model should be able to fill prescriptions within hours or days, which might explain why some pharmacies in the Washington, DC area survey did not have a 30-day supply on hand, he said. However, Dr. Ganio noted that the causes of drug shortages are complex and multi-factorial. For now, he said there have been no oral minoxidil shortage reports since mid-September.

But Dr. Friedman said some of his patients have waited weeks for a new supply – and that no one is aware of the problem until the last moment.

The lack of alerts or transparency “also erodes the physician-patient relationship because there’s this expectation of the patient that we should have known this,” said Dr. Friedman.

Dr. Friedman reports no relevant financial relationships.

This story was updated on 11/2/2023.

A recent survey found that less than half of pharmacies in the Washington area had a 30-day supply of either 2.5-mg or 10-mg tablets of oral minoxidil, used for both hair loss and hypertension.

Patients are not finding out until they go to pick up their prescription, which can result in an interruption of treatment – and, potentially a loss of hard-earned hair gain, said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was the lead author of the survey, published online on Oct. 26 as a research letter in the Journal of Drugs in Dermatology.

Going off low-dose oral minoxidil may spark a telogen effluvium event, and that is very disappointing to patients, Dr. Friedman told this news organization.

“There needs to be some system that alerts us,” he said. “Even if it’s a minor shortage, just so we’re aware. We can then prepare patients,” he added, noting that it would be better for someone to be taking a lower-than-normal dose rather than no medication at all while they wait for a refill.

Minoxidil has long been approved in a topical formulation to treat androgenetic alopecia, but a low-dose oral form has gained currency in the wake of findings that it might more effectively treat hair loss, and is without side effects. A New York Times article in August 2022 touting low-dose oral minoxidil as a cheap and effective hair loss drug appeared to ignite interest in this option. In May, 2023, researchers reporting in JAMA Network Open demonstrated a significant uptick in prescriptions for oral minoxidil in the wake of the article’s publication.

Oral minoxidil is approved by the Food and Drug Administration only for hypertension, but dermatologists are prescribing it off-label at a lower dose for hair loss. Dr. Friedman said it’s not clear whether the shortages his team found are national in scope, or whether they are a result of increased demand, or other factors.

After several patients told him they were having trouble filling minoxidil prescriptions, and colleagues said they’d had patients with similar experiences, Dr. Friedman and his colleagues undertook the survey. In the first week of October 2023, they contacted 277 pharmacies by phone in Washington and surrounding Virginia and Maryland counties. The pharmacies were CVS, Giant, Walgreens, and Harris Teeter.

Of the 277 pharmacies they contacted, 40% (111) reported availability of 2.5-mg tablets for a 30-day supply, and just under 30% (82) reported having 10-mg tablets for a 30-day supply.

For treating hair loss, most patients are prescribed 2.5-mg pills, with starting doses ranging from 0.625 mg to 5 mg twice a day, Dr. Friedman said. The 10-mg dose is more frequently prescribed for hypertension.

Only 28% (19 of 67) of the Maryland pharmacies had 30-day supplies of 2.5-mg tablets on hand, and just 22% (15) of the Maryland pharmacies had 30-day supplies of 10-mg tablets. In Northern Virginia, 44% (63 of 143) of the pharmacies had 30-day supplies of the 2.5 mg tablets, as did just 43% (29 of 67) of the Washington pharmacies.

Dr. Friedman said he has started giving patients paper prescriptions they can use to shop around, rather than electronically sending a prescription to a particular pharmacy.

Neither the Food and Drug Administration nor the American Society of Health System Pharmacists lists oral minoxidil as a drug in shortage.

Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, said the organization received a report from wholesalers in mid-September showing spotty oral minoxidil availability, with the drug on backorder with some manufacturers.  ASHP's shortages list is compiled from reports from physicians, manufacturers and wholesalers, he said.

Under what he calls "blue sky conditions," pharmacies using a just-in-time inventory model should be able to fill prescriptions within hours or days, which might explain why some pharmacies in the Washington, DC area survey did not have a 30-day supply on hand, he said. However, Dr. Ganio noted that the causes of drug shortages are complex and multi-factorial. For now, he said there have been no oral minoxidil shortage reports since mid-September.

But Dr. Friedman said some of his patients have waited weeks for a new supply – and that no one is aware of the problem until the last moment.

The lack of alerts or transparency “also erodes the physician-patient relationship because there’s this expectation of the patient that we should have known this,” said Dr. Friedman.

Dr. Friedman reports no relevant financial relationships.

This story was updated on 11/2/2023.

A recent survey found that less than half of pharmacies in the Washington area had a 30-day supply of either 2.5-mg or 10-mg tablets of oral minoxidil, used for both hair loss and hypertension.

Patients are not finding out until they go to pick up their prescription, which can result in an interruption of treatment – and, potentially a loss of hard-earned hair gain, said Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, who was the lead author of the survey, published online on Oct. 26 as a research letter in the Journal of Drugs in Dermatology.

Going off low-dose oral minoxidil may spark a telogen effluvium event, and that is very disappointing to patients, Dr. Friedman told this news organization.

“There needs to be some system that alerts us,” he said. “Even if it’s a minor shortage, just so we’re aware. We can then prepare patients,” he added, noting that it would be better for someone to be taking a lower-than-normal dose rather than no medication at all while they wait for a refill.

Minoxidil has long been approved in a topical formulation to treat androgenetic alopecia, but a low-dose oral form has gained currency in the wake of findings that it might more effectively treat hair loss, and is without side effects. A New York Times article in August 2022 touting low-dose oral minoxidil as a cheap and effective hair loss drug appeared to ignite interest in this option. In May, 2023, researchers reporting in JAMA Network Open demonstrated a significant uptick in prescriptions for oral minoxidil in the wake of the article’s publication.

Oral minoxidil is approved by the Food and Drug Administration only for hypertension, but dermatologists are prescribing it off-label at a lower dose for hair loss. Dr. Friedman said it’s not clear whether the shortages his team found are national in scope, or whether they are a result of increased demand, or other factors.

After several patients told him they were having trouble filling minoxidil prescriptions, and colleagues said they’d had patients with similar experiences, Dr. Friedman and his colleagues undertook the survey. In the first week of October 2023, they contacted 277 pharmacies by phone in Washington and surrounding Virginia and Maryland counties. The pharmacies were CVS, Giant, Walgreens, and Harris Teeter.

Of the 277 pharmacies they contacted, 40% (111) reported availability of 2.5-mg tablets for a 30-day supply, and just under 30% (82) reported having 10-mg tablets for a 30-day supply.

For treating hair loss, most patients are prescribed 2.5-mg pills, with starting doses ranging from 0.625 mg to 5 mg twice a day, Dr. Friedman said. The 10-mg dose is more frequently prescribed for hypertension.

Only 28% (19 of 67) of the Maryland pharmacies had 30-day supplies of 2.5-mg tablets on hand, and just 22% (15) of the Maryland pharmacies had 30-day supplies of 10-mg tablets. In Northern Virginia, 44% (63 of 143) of the pharmacies had 30-day supplies of the 2.5 mg tablets, as did just 43% (29 of 67) of the Washington pharmacies.

Dr. Friedman said he has started giving patients paper prescriptions they can use to shop around, rather than electronically sending a prescription to a particular pharmacy.

Neither the Food and Drug Administration nor the American Society of Health System Pharmacists lists oral minoxidil as a drug in shortage.

Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, said the organization received a report from wholesalers in mid-September showing spotty oral minoxidil availability, with the drug on backorder with some manufacturers.  ASHP's shortages list is compiled from reports from physicians, manufacturers and wholesalers, he said.

Under what he calls "blue sky conditions," pharmacies using a just-in-time inventory model should be able to fill prescriptions within hours or days, which might explain why some pharmacies in the Washington, DC area survey did not have a 30-day supply on hand, he said. However, Dr. Ganio noted that the causes of drug shortages are complex and multi-factorial. For now, he said there have been no oral minoxidil shortage reports since mid-September.

But Dr. Friedman said some of his patients have waited weeks for a new supply – and that no one is aware of the problem until the last moment.

The lack of alerts or transparency “also erodes the physician-patient relationship because there’s this expectation of the patient that we should have known this,” said Dr. Friedman.

Dr. Friedman reports no relevant financial relationships.

This story was updated on 11/2/2023.

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

A version of this article first appeared on Medscape.com.

TOPLINE:

New research suggests terminating metformin may raise the risk for dementia in older adults with type 2 diabetes, providing more evidence of metformin’s potential neuroprotective effects.

METHODOLOGY:

• Researchers evaluated the association between discontinuing metformin for reasons unrelated to kidney dysfunction and dementia incidence.
• The cohort included 12,220 Kaiser Permanente Northern California members who stopped metformin early (with normal kidney function) and 29,126 routine metformin users.
• The cohort of early terminators was 46% women with an average age of 59 years at the start of metformin prescription. The cohort continuing metformin was 47% women, with a start age of 61 years.

TAKEAWAY:

• Adults who stopped metformin early were 21% more likely to be diagnosed with dementia during follow up (hazard ratio, 1.21; 95% confidence interval, 1.12-1.30), compared with routine metformin users.
• This association was largely independent of changes in A1c level and insulin usage.

IN PRACTICE:

The findings “corroborate the largely consistent evidence from other observational studies showing an association between metformin use and lower dementia incidence [and] may have important implications for clinical treatment of adults with diabetes,” the authors write.

SOURCE:

The study, with first author Scott Zimmerman, MPH, University of California, San Francisco, was published online  in JAMA Network Open.

LIMITATIONS:

Dementia diagnosis was obtained based on medical records. Factors such as race, ethnicity, or time on metformin were not evaluated. Information on the exact reason for stopping metformin was not available.

DISCLOSURES:

The study was funded by grants from the National Institutes of Health, National Institute on Aging. Mr. Zimmerman owns stock in AbbVie, Gilead Sciences, CRISPR Therapeutics, and Abbott Laboratories. Disclosure for the other study authors can be found with the original article.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved ustekinumab-auub (Wezlana) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions. This is the first approval for a ustekinumab biosimilar in the United States.

Ustekinumab-auub was also granted an interchangeability designation, meaning that, depending on state law, a pharmacist may substitute the biosimilar for the reference product without consulting the prescribing provider.

“Today’s approval exemplifies the FDA’s longstanding commitment to support a competitive marketplace for biological products,” Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval can empower patients by helping to increase access to safe, effective, and high-quality medications at potentially lower cost.”

Ustekinumab, manufactured by Johnson & Johnson, targets interleukin-12 and IL-23 and was first approved in 2009. Ustekinumab-auub was developed by Amgen.

Ustekinumab-auub is approved for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderate to severely active Crohn’s disease, and moderate to severely active ulcerative colitis. It is also approved for pediatric patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis.

The approval was based on “comprehensive review of scientific evidence,” including “comparisons of the products on an analytical level using an extensive battery of chemical and biological tests and biological assays that confirmed similarity in the structural and functional features of Wezlana and Stelara (including those known to impact safety and efficacy), and comparative human pharmacokinetic data, clinical immunogenicity data, and other clinical safety and effectiveness data,” the FDA said.

Some common side effects of ustekinumab-auub include nasopharyngitis, upper respiratory tract infection, headache, fatigue, and nausea. The most severe side effect of the biosimilar, as with the reference drug ustekinumab, is infection.

The product launch of ustekinumab-auub will be delayed as a part of a settlement of Johnson & Johnson’s lawsuit against Amgen, according to Reuters. The details of the settlement are confidential, but it was stated that the biosimilar would be available by Jan. 1, 2025.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved ustekinumab-auub (Wezlana) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions. This is the first approval for a ustekinumab biosimilar in the United States.

Ustekinumab-auub was also granted an interchangeability designation, meaning that, depending on state law, a pharmacist may substitute the biosimilar for the reference product without consulting the prescribing provider.

“Today’s approval exemplifies the FDA’s longstanding commitment to support a competitive marketplace for biological products,” Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval can empower patients by helping to increase access to safe, effective, and high-quality medications at potentially lower cost.”

Ustekinumab, manufactured by Johnson & Johnson, targets interleukin-12 and IL-23 and was first approved in 2009. Ustekinumab-auub was developed by Amgen.

Ustekinumab-auub is approved for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderate to severely active Crohn’s disease, and moderate to severely active ulcerative colitis. It is also approved for pediatric patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis.

The approval was based on “comprehensive review of scientific evidence,” including “comparisons of the products on an analytical level using an extensive battery of chemical and biological tests and biological assays that confirmed similarity in the structural and functional features of Wezlana and Stelara (including those known to impact safety and efficacy), and comparative human pharmacokinetic data, clinical immunogenicity data, and other clinical safety and effectiveness data,” the FDA said.

Some common side effects of ustekinumab-auub include nasopharyngitis, upper respiratory tract infection, headache, fatigue, and nausea. The most severe side effect of the biosimilar, as with the reference drug ustekinumab, is infection.

The product launch of ustekinumab-auub will be delayed as a part of a settlement of Johnson & Johnson’s lawsuit against Amgen, according to Reuters. The details of the settlement are confidential, but it was stated that the biosimilar would be available by Jan. 1, 2025.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved ustekinumab-auub (Wezlana) as a biosimilar to ustekinumab (Stelara) for the treatment of multiple inflammatory conditions. This is the first approval for a ustekinumab biosimilar in the United States.

Ustekinumab-auub was also granted an interchangeability designation, meaning that, depending on state law, a pharmacist may substitute the biosimilar for the reference product without consulting the prescribing provider.

“Today’s approval exemplifies the FDA’s longstanding commitment to support a competitive marketplace for biological products,” Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research, said in a statement. “This approval can empower patients by helping to increase access to safe, effective, and high-quality medications at potentially lower cost.”

Ustekinumab, manufactured by Johnson & Johnson, targets interleukin-12 and IL-23 and was first approved in 2009. Ustekinumab-auub was developed by Amgen.

Ustekinumab-auub is approved for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, active psoriatic arthritis, moderate to severely active Crohn’s disease, and moderate to severely active ulcerative colitis. It is also approved for pediatric patients aged 6 years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and active psoriatic arthritis.

The approval was based on “comprehensive review of scientific evidence,” including “comparisons of the products on an analytical level using an extensive battery of chemical and biological tests and biological assays that confirmed similarity in the structural and functional features of Wezlana and Stelara (including those known to impact safety and efficacy), and comparative human pharmacokinetic data, clinical immunogenicity data, and other clinical safety and effectiveness data,” the FDA said.

Some common side effects of ustekinumab-auub include nasopharyngitis, upper respiratory tract infection, headache, fatigue, and nausea. The most severe side effect of the biosimilar, as with the reference drug ustekinumab, is infection.

The product launch of ustekinumab-auub will be delayed as a part of a settlement of Johnson & Johnson’s lawsuit against Amgen, according to Reuters. The details of the settlement are confidential, but it was stated that the biosimilar would be available by Jan. 1, 2025.

A version of this article first appeared on Medscape.com.

TOPLINE:

Severe mental illness (SMI) has been linked to a 50% increased risk for all-cause mortality risk after COVID-19, a large population-based study suggests.

METHODOLOGY:

• Investigators analyzed data from the Clinical Practice Research Datalink database, which contains health information on 13.5 million patients receiving care from family practices in England and Northern Ireland.
• The study included participants with SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder.
• Participants were aged 5 years or older with a SARS-CoV-2 infection recorded between Feb. 1, 2020, and March 31, 2021, spanning two waves of the pandemic.
• Death rates among participants with SMI and COVID-19 (n = 7,150; 56% female) were compared with those in a control group of participants without SMI who had been diagnosed with COVID-19 (n = 650,000; 55% female).

TAKEAWAY:

• Participants with SMI and COVID-19 had a 53% higher risk for death than those in the non-SMI control group (adjusted hazard ratio, 1.53; 95% confidence interval, 1.39-1.68).
• Black Caribbean/Black African participants were more likely than White participants to die of COVID-19 (aHR, 1.22; 95% CI, 1.12-1.34), although ethnicity was not recorded in 30% of participants.
• After SARS-CoV-2 infection, for every additional multimorbid condition, the aHR for death increased by 6% in the SMI group and 16% in the non-SMI group (P = .001). Some of these conditions included hypertension, heart disease, diabetes, kidney disease, depression, and anxiety.

IN PRACTICE:

“From a public health perspective, our study has emphasized the need for early and timely preventative interventions (e.g. vaccination) for the SMI population. Future studies are needed to disentangle the complex biological and psychosocial factors, and health care pathways, that have led to the greater mortality rates in the SMI population,” the authors write.

SOURCE:

Jayati Das-Munshi, MD, of Kings College London, led the study, which was published online in the British Journal of Psychiatry. The study was funded by the Health Foundation.

LIMITATIONS:

COVID-19 may have been underdiagnosed or underreported in the records studied. Also, investigators did not have information about cause of death.

DISCLOSURES:

One author received funding from Janssen, GSK, and Takeda. All other authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Severe mental illness (SMI) has been linked to a 50% increased risk for all-cause mortality risk after COVID-19, a large population-based study suggests.

METHODOLOGY:

• Investigators analyzed data from the Clinical Practice Research Datalink database, which contains health information on 13.5 million patients receiving care from family practices in England and Northern Ireland.
• The study included participants with SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder.
• Participants were aged 5 years or older with a SARS-CoV-2 infection recorded between Feb. 1, 2020, and March 31, 2021, spanning two waves of the pandemic.
• Death rates among participants with SMI and COVID-19 (n = 7,150; 56% female) were compared with those in a control group of participants without SMI who had been diagnosed with COVID-19 (n = 650,000; 55% female).

TAKEAWAY:

• Participants with SMI and COVID-19 had a 53% higher risk for death than those in the non-SMI control group (adjusted hazard ratio, 1.53; 95% confidence interval, 1.39-1.68).
• Black Caribbean/Black African participants were more likely than White participants to die of COVID-19 (aHR, 1.22; 95% CI, 1.12-1.34), although ethnicity was not recorded in 30% of participants.
• After SARS-CoV-2 infection, for every additional multimorbid condition, the aHR for death increased by 6% in the SMI group and 16% in the non-SMI group (P = .001). Some of these conditions included hypertension, heart disease, diabetes, kidney disease, depression, and anxiety.

IN PRACTICE:

“From a public health perspective, our study has emphasized the need for early and timely preventative interventions (e.g. vaccination) for the SMI population. Future studies are needed to disentangle the complex biological and psychosocial factors, and health care pathways, that have led to the greater mortality rates in the SMI population,” the authors write.

SOURCE:

Jayati Das-Munshi, MD, of Kings College London, led the study, which was published online in the British Journal of Psychiatry. The study was funded by the Health Foundation.

LIMITATIONS:

COVID-19 may have been underdiagnosed or underreported in the records studied. Also, investigators did not have information about cause of death.

DISCLOSURES:

One author received funding from Janssen, GSK, and Takeda. All other authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Severe mental illness (SMI) has been linked to a 50% increased risk for all-cause mortality risk after COVID-19, a large population-based study suggests.

METHODOLOGY:

• Investigators analyzed data from the Clinical Practice Research Datalink database, which contains health information on 13.5 million patients receiving care from family practices in England and Northern Ireland.
• The study included participants with SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder.
• Participants were aged 5 years or older with a SARS-CoV-2 infection recorded between Feb. 1, 2020, and March 31, 2021, spanning two waves of the pandemic.
• Death rates among participants with SMI and COVID-19 (n = 7,150; 56% female) were compared with those in a control group of participants without SMI who had been diagnosed with COVID-19 (n = 650,000; 55% female).

TAKEAWAY:

• Participants with SMI and COVID-19 had a 53% higher risk for death than those in the non-SMI control group (adjusted hazard ratio, 1.53; 95% confidence interval, 1.39-1.68).
• Black Caribbean/Black African participants were more likely than White participants to die of COVID-19 (aHR, 1.22; 95% CI, 1.12-1.34), although ethnicity was not recorded in 30% of participants.
• After SARS-CoV-2 infection, for every additional multimorbid condition, the aHR for death increased by 6% in the SMI group and 16% in the non-SMI group (P = .001). Some of these conditions included hypertension, heart disease, diabetes, kidney disease, depression, and anxiety.

IN PRACTICE:

“From a public health perspective, our study has emphasized the need for early and timely preventative interventions (e.g. vaccination) for the SMI population. Future studies are needed to disentangle the complex biological and psychosocial factors, and health care pathways, that have led to the greater mortality rates in the SMI population,” the authors write.

SOURCE:

Jayati Das-Munshi, MD, of Kings College London, led the study, which was published online in the British Journal of Psychiatry. The study was funded by the Health Foundation.

LIMITATIONS:

COVID-19 may have been underdiagnosed or underreported in the records studied. Also, investigators did not have information about cause of death.

DISCLOSURES:

One author received funding from Janssen, GSK, and Takeda. All other authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

Vasomotor symptoms the sudden rises in body temperature that affect about 75% of menopausal women, have drawn interest after the approval of a new oral drug and research linking hot flashes to Alzheimer’s, heart disease, and stroke. 

Now entering the discussion are researchers from the University of Massachusetts, Amherst, and Embr Labs (a Massachusetts Institute of Technology spinoff) who say they’ve developed a machine-learning algorithm that can predict a hot flash. 

Their idea is to combine this algorithm with a product called Embr Wave, a watch-like wearable that can emit coolness (or warmth) to the sensitive skin on the inside of the wrist, providing whole-body relief. The device, which sells for $299, is already touted as a way to manage menopausal hot flashes. 

But once the algorithm is added, the device will be able to “continuously monitor physiological signals – skin temperature, body temperature, sweating, activity level, or heart rate – and identify early indicators that a hot flash is building,” said Michael Busa, PhD, director of the Center for Human Health and Performance at UMass Amherst, who led the team that developed the algorithm.

That data would be sent to a computing platform in the cloud, where the algorithm can flag signs of an impending hot flash, Dr. Busa said. The device would automatically prompt cooling in less than a second, which could effectively stop the hot flash in its tracks or at least help to take the edge off. 
 

Exploring cooling therapy for hot flashes

“There is always tremendous interest in anything that is nonhormonal and effective in treatment of hot flashes,” said Karen Adams, MD, an ob.gyn. and director of the menopause and healthy aging program at Stanford (Calif.) University. (Dr. Adams was not involved in developing this technology.) 

Hormone therapy is the primary treatment, easing hot flashes in 3-4 weeks, Dr. Adams said. “But some women do not want to take estrogen, or should not due to medical contraindications.” 

Hormone therapy is generally not recommended for people with a history of breast cancer, blood clots, or diseases of their heart or blood vessels. Recent research presented at the annual meeting of the Menopause Society found that hormone therapy may not work as well in women with obesity. 

For nonhormonal treatments, the Food and Drug Administration cleared the oral med fezolinetant (Veozah) in May. Antidepressant medications can also be used as a first-line treatment in those who can’t take estrogen. Another oral drug, elinzanetant, is in late-stage clinical trials. 

But there has been little clinical investigation – only two small studies, Dr. Adams said – examining cooling therapy as a treatment for hot flashes. That’s something the makers of this device hope to change. 

“Despite the fact that seeking cooling relief is a woman’s immediate natural response to the onset of a hot flash, there is limited work done to understand the benefits of this natural therapy,” said Matthew Smith, PhD, chief technology officer at Embr Labs. “This is in part because the technology didn’t exist to deliver cooling in an immediate, reproducible manner.”

The algorithm’s performance has been benchmarked using data from women having hot flashes, Dr. Smith said. Results have been submitted for publication.

The Embr Wave has been shown to help menopausal women with hot flashes sleep better. It has also been tested as a therapy for hot flashes related to cancer treatment. 

But to truly evaluate the device as a treatment for hot flashes, it should be tested in randomized trials including a “sham treatment arm” – where some people get the real treatment while others get the sham treatment, Dr. Adams said. 

“Device studies tend to have high placebo response rates that can only be truly evaluated when there is a sham treatment in the study,” she said. “If such a device were shown to be safe and effective, we would absolutely recommend it. But we’re a long way from that.”

A version of this article appeared on WebMD.com.

Vasomotor symptoms the sudden rises in body temperature that affect about 75% of menopausal women, have drawn interest after the approval of a new oral drug and research linking hot flashes to Alzheimer’s, heart disease, and stroke. 

Now entering the discussion are researchers from the University of Massachusetts, Amherst, and Embr Labs (a Massachusetts Institute of Technology spinoff) who say they’ve developed a machine-learning algorithm that can predict a hot flash. 

Their idea is to combine this algorithm with a product called Embr Wave, a watch-like wearable that can emit coolness (or warmth) to the sensitive skin on the inside of the wrist, providing whole-body relief. The device, which sells for $299, is already touted as a way to manage menopausal hot flashes. 

But once the algorithm is added, the device will be able to “continuously monitor physiological signals – skin temperature, body temperature, sweating, activity level, or heart rate – and identify early indicators that a hot flash is building,” said Michael Busa, PhD, director of the Center for Human Health and Performance at UMass Amherst, who led the team that developed the algorithm.

That data would be sent to a computing platform in the cloud, where the algorithm can flag signs of an impending hot flash, Dr. Busa said. The device would automatically prompt cooling in less than a second, which could effectively stop the hot flash in its tracks or at least help to take the edge off. 
 

Exploring cooling therapy for hot flashes

“There is always tremendous interest in anything that is nonhormonal and effective in treatment of hot flashes,” said Karen Adams, MD, an ob.gyn. and director of the menopause and healthy aging program at Stanford (Calif.) University. (Dr. Adams was not involved in developing this technology.) 

Hormone therapy is the primary treatment, easing hot flashes in 3-4 weeks, Dr. Adams said. “But some women do not want to take estrogen, or should not due to medical contraindications.” 

Hormone therapy is generally not recommended for people with a history of breast cancer, blood clots, or diseases of their heart or blood vessels. Recent research presented at the annual meeting of the Menopause Society found that hormone therapy may not work as well in women with obesity. 

For nonhormonal treatments, the Food and Drug Administration cleared the oral med fezolinetant (Veozah) in May. Antidepressant medications can also be used as a first-line treatment in those who can’t take estrogen. Another oral drug, elinzanetant, is in late-stage clinical trials. 

But there has been little clinical investigation – only two small studies, Dr. Adams said – examining cooling therapy as a treatment for hot flashes. That’s something the makers of this device hope to change. 

“Despite the fact that seeking cooling relief is a woman’s immediate natural response to the onset of a hot flash, there is limited work done to understand the benefits of this natural therapy,” said Matthew Smith, PhD, chief technology officer at Embr Labs. “This is in part because the technology didn’t exist to deliver cooling in an immediate, reproducible manner.”

The algorithm’s performance has been benchmarked using data from women having hot flashes, Dr. Smith said. Results have been submitted for publication.

The Embr Wave has been shown to help menopausal women with hot flashes sleep better. It has also been tested as a therapy for hot flashes related to cancer treatment. 

But to truly evaluate the device as a treatment for hot flashes, it should be tested in randomized trials including a “sham treatment arm” – where some people get the real treatment while others get the sham treatment, Dr. Adams said. 

“Device studies tend to have high placebo response rates that can only be truly evaluated when there is a sham treatment in the study,” she said. “If such a device were shown to be safe and effective, we would absolutely recommend it. But we’re a long way from that.”

A version of this article appeared on WebMD.com.

Vasomotor symptoms the sudden rises in body temperature that affect about 75% of menopausal women, have drawn interest after the approval of a new oral drug and research linking hot flashes to Alzheimer’s, heart disease, and stroke. 

Now entering the discussion are researchers from the University of Massachusetts, Amherst, and Embr Labs (a Massachusetts Institute of Technology spinoff) who say they’ve developed a machine-learning algorithm that can predict a hot flash. 

Their idea is to combine this algorithm with a product called Embr Wave, a watch-like wearable that can emit coolness (or warmth) to the sensitive skin on the inside of the wrist, providing whole-body relief. The device, which sells for $299, is already touted as a way to manage menopausal hot flashes. 

But once the algorithm is added, the device will be able to “continuously monitor physiological signals – skin temperature, body temperature, sweating, activity level, or heart rate – and identify early indicators that a hot flash is building,” said Michael Busa, PhD, director of the Center for Human Health and Performance at UMass Amherst, who led the team that developed the algorithm.

That data would be sent to a computing platform in the cloud, where the algorithm can flag signs of an impending hot flash, Dr. Busa said. The device would automatically prompt cooling in less than a second, which could effectively stop the hot flash in its tracks or at least help to take the edge off. 
 

Exploring cooling therapy for hot flashes

“There is always tremendous interest in anything that is nonhormonal and effective in treatment of hot flashes,” said Karen Adams, MD, an ob.gyn. and director of the menopause and healthy aging program at Stanford (Calif.) University. (Dr. Adams was not involved in developing this technology.) 

Hormone therapy is the primary treatment, easing hot flashes in 3-4 weeks, Dr. Adams said. “But some women do not want to take estrogen, or should not due to medical contraindications.” 

Hormone therapy is generally not recommended for people with a history of breast cancer, blood clots, or diseases of their heart or blood vessels. Recent research presented at the annual meeting of the Menopause Society found that hormone therapy may not work as well in women with obesity. 

For nonhormonal treatments, the Food and Drug Administration cleared the oral med fezolinetant (Veozah) in May. Antidepressant medications can also be used as a first-line treatment in those who can’t take estrogen. Another oral drug, elinzanetant, is in late-stage clinical trials. 

But there has been little clinical investigation – only two small studies, Dr. Adams said – examining cooling therapy as a treatment for hot flashes. That’s something the makers of this device hope to change. 

“Despite the fact that seeking cooling relief is a woman’s immediate natural response to the onset of a hot flash, there is limited work done to understand the benefits of this natural therapy,” said Matthew Smith, PhD, chief technology officer at Embr Labs. “This is in part because the technology didn’t exist to deliver cooling in an immediate, reproducible manner.”

The algorithm’s performance has been benchmarked using data from women having hot flashes, Dr. Smith said. Results have been submitted for publication.

The Embr Wave has been shown to help menopausal women with hot flashes sleep better. It has also been tested as a therapy for hot flashes related to cancer treatment. 

But to truly evaluate the device as a treatment for hot flashes, it should be tested in randomized trials including a “sham treatment arm” – where some people get the real treatment while others get the sham treatment, Dr. Adams said. 

“Device studies tend to have high placebo response rates that can only be truly evaluated when there is a sham treatment in the study,” she said. “If such a device were shown to be safe and effective, we would absolutely recommend it. But we’re a long way from that.”

A version of this article appeared on WebMD.com.

Prescriptions for semaglutide jumped 150% in the past year, with an 80% increase in prescriptions written per provider, new data suggest.

Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.

Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.

General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.

“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.

Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”

Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
 

Are patients actually getting the prescribed medications?

However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”

Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.

Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”

Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.

Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”

Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”

The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.

A version of this article appeared on Medscape.com.

Prescriptions for semaglutide jumped 150% in the past year, with an 80% increase in prescriptions written per provider, new data suggest.

Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.

Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.

General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.

“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.

Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”

Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
 

Are patients actually getting the prescribed medications?

However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”

Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.

Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”

Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.

Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”

Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”

The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.

A version of this article appeared on Medscape.com.

Prescriptions for semaglutide jumped 150% in the past year, with an 80% increase in prescriptions written per provider, new data suggest.

Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.

Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.

General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.

“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.

Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”

Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
 

Are patients actually getting the prescribed medications?

However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”

Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.

Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”

Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.

Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”

Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”

The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.

A version of this article appeared on Medscape.com.

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

A version of this article first appeared on Medscape.com.

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

A version of this article first appeared on Medscape.com.

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

A version of this article first appeared on Medscape.com.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

Short-term use of JAK inhibitors for a dermatologic indication appears to not be associated with an increased risk of all-cause mortality, major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE), results from a systematic literature review, and meta-analysis showed.

“There remains a knowledge gap regarding the risk of JAK inhibitor use and VTE and/or MACE in the dermatologic population,” researchers led by Michael S. Garshick, MD, a cardiologist at New York University Langone Health, wrote in their study, which was published online in JAMA Dermatology . “Pooled safety studies suggest that the risk of MACE and VTE may be lower in patients treated with JAK inhibitors for a dermatologic indication than the risk observed in the ORAL Surveillance study, which may be related to the younger age and better health status of those enrolled in trials for dermatologic indications.” The results of that study, which included patients with rheumatoid arthritis only, resulted in the addition of a boxed warning in the labels for topical and oral JAK inhibitors regarding the increased risk of MACE, VTE, serious infections, malignancies, and death .

For the review – thought to be the first to specifically evaluate these risks for dermatologic indications – the researchers searched PubMed and ClinicalTrials.gov from inception through April 1, 2023, for phase 3 dermatology randomized clinical trials (RCTs) to evaluate the risk of MACE, VTE, and all-cause mortality with JAK inhibitors, compared with placebo or an active comparator in the treatment of immune-mediated inflammatory skin diseases. They followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used a random-effects model and the DerSimonian-Laird method to calculate adverse events with odds ratios.

The database search yielded 35 RCTs with a total of 20,651 patients. Their mean age was 38.5 years, 54% were male, and the mean follow-up time was 4.9 months. Of the 35 trials, most (21) involved patients with atopic dermatitis, followed by psoriasis/psoriatic arthritis (9 trials), alopecia areata (3 trials) and vitiligo (2 trials).

The researchers found no significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (odds ratio, 0.83; 95% confidence interval, 0.44-1.57) or in VTE (OR, 0.52; 95% CI, 0.26-1.04).

In a secondary analysis, which included additional psoriatic arthritis RCTs, no significant differences between the treatment and placebo/active comparator groups were observed. Similarly, subgroup analyses of oral versus topical JAK inhibitors and a sensitivity analysis that excluded pediatric trials showed no significant differences between patients exposed to JAK inhibitors and those not exposed.

The researchers acknowledged certain limitations of the review, including the lack of access to patient-level data, the fact that most trials only included short-term follow-up, and that the findings have limited generalizability to an older patient population. “It remains unclear if the cardiovascular risks of JAK inhibitors are primarily due to patient level cardiovascular risk factors or are drug mediated,” they concluded. “Dermatologists should carefully select patients and assess baseline cardiovascular risk factors when considering JAK therapy. Cardiovascular risk assessment should continue for the duration of treatment.”

Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, who was asked to comment on the study results, characterized the findings as reassuring to dermatologists who may be reluctant to initiate therapy with JAK inhibitors based on concerns about safety signals for MACE, VTE, and all-cause mortality.

“These data systematically show that across medications and across conditions, there doesn’t appear to be an increased signal for these events during the short-term, placebo-controlled period which generally spans a few months in most studies,” he told this news organization. The findings, he added, “align well with our clinical experience to date for JAK inhibitor use in inflammatory skin disease. Short-term safety, particularly in relation to boxed warning events such MACE, VTE, and all-cause mortality, have generally been favorable with real-world use. It’s good to have a rigorous statistical analysis to refer to when setting patient expectations.”

However, he noted that these data only examined short-term safety during the placebo or active comparator-controlled periods. “Considering that events like MACE or VTE may take many months or years to manifest, continued long-term data generation is needed to fully answer the question of risk,” he said.

Dr. Garshick disclosed that he received grants from Pfizer and personal fees from Bristol Myers Squibb during the conduct of the study and personal fees from Kiniksa Pharmaceuticals outside the submitted work. Several other coauthors reported having advisory board roles and/or having received funding or support from several pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including those that develop JAK inhibitors.

CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.

But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the development of a biomaterial known as microporous annealed particle (MAP) hydrogel, which in preclinical studies has been shown to trigger the immune system leading to improved tissue repair and healthier, stronger skin.

“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”

Dr. Scumpia

Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”

Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”

Approaches to skin regeneration

Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”

Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”

Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”

The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.

During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”

In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.

Clinical trials planned

The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.

Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.

CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.

But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the development of a biomaterial known as microporous annealed particle (MAP) hydrogel, which in preclinical studies has been shown to trigger the immune system leading to improved tissue repair and healthier, stronger skin.

“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”

Dr. Scumpia

Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”

Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”

Approaches to skin regeneration

Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”

Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”

Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”

The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.

During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”

In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.

Clinical trials planned

The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.

Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.

CARLSBAD, CALIF. – For the estimated 10 million wounds that clinicians treat in the United States each year resulting from surgical procedures, trauma, burns, and other causes, the best outcome is a scar, a fibrotic dermis with a flattened epidermis that contains no sweat glands, no pilosebaceous units, and impaired nerve function.

But what if the outcome was skin regeneration instead of scar formation? At the annual symposium of the California Society of Dermatology & Dermatologic Surgery, Philip O. Scumpia, MD, PhD, described the development of a biomaterial known as microporous annealed particle (MAP) hydrogel, which in preclinical studies has been shown to trigger the immune system leading to improved tissue repair and healthier, stronger skin.

“We’re preprogrammed to undergo scarring,” said Dr. Scumpia, associate professor of dermatology at the University of California, Los Angeles. “Tissue fibrosis is an evolutionary process” where a fibrotic matrix is deposited “as quickly as possible to close the gap caused by an injury,” he noted. “All of the cues in the normal wound healing process result in fibrosis, but we want to move from scarring to tissue regeneration. The goal is to make something that can shift from this evolutionary process, and it’s proven to be inherently difficult.”

Dr. Scumpia

Common approaches to wound treatment include simple and advanced dressings, negative pressure, and hyperbaric oxygen. For wounds that persist beyond 30 days, advanced treatment options include decellularized grafts such as placental membranes, amniotic membranes, and acellular dermal matrices. “There are also cellularized grafts such as dressings that contain neonatal dermal fibroblasts,” which are expensive, said Dr. Scumpia, director of dermatopathology at the West Los Angeles VA Medical Center. “There are also semi-synthetic grafts such as single or double layer dermal replacement templates and synthetic dermal substitutes in the form of sheets or foam. All of these can help with wound coverage and help chronic wounds close on their own.”

Meanwhile, tissue regeneration – or efforts to restore tissue to its original functionality – include growth factors, stem cells, or replacement extracellular matrix (skin substitutes), or a combination. “Bioengineered dressings and bioengineered skin substitutes have shown modest improvement in wound healing but not tissue regeneration,” Dr. Scumpia said. “At best, we can accelerate scar formation and close the wound quicker, but nothing has been shown to regenerate tissue.”

Approaches to skin regeneration

Studies from the embryology literature have helped researchers develop better approaches to skin regeneration. For example, fetal skin heals without scarring when injured. “Hairs form from placodes, then sebaceous glands form, and fibroblasts that are part of the papillary mesenchymal body expressing special factors such as engrailed or CRABP1 drive hair follicle formation,” he said. “Many studies have shown that sonic hedgehog signaling, and Wnt/beta-catenin signaling can play a role in the development of new hair follicles. Also, fibroblasts in the dermis can drive hair follicle formation.”

Researchers are also learning about tissue regeneration from mouse models. For example, African spiny mice have been shown to heal regeneratively. “If you make wounds large enough on lab mice, the center heals regeneratively,” Dr. Scumpia said. “What’s interesting is that these same signals are present in embryonic hair follicle development. Why is this important? Who wants a hairy scar? It’s an organized structure that develops in the wound. That can help us understand what we need to put in so that our body regenerates on its own. In mouse models, the immune system has been shown to play a role in regeneration.”

Expanding on initial work conducted at UCLA, Dr. Scumpia and his colleagues founded San Diego-based Tempo Therapeutics, which is commercializing the MAP hydrogel to mimic the natural porosity and stiffness of skin. They sought to develop a new biomaterial, he said, noting that “the skin is porous on a microscale level, allowing cells to infiltrate different areas.” And the problem with existing biomaterials “is that they don’t incorporate into the skin very well,” he explained. “They’re usually stiff and rubbery and can cause a foreign body reaction, which can result in fibrous encapsulation and inflammation.”

The MAP hydrogel is composed of randomly packed “microsphere building blocks,” including an amino acid that promotes an immune response. When injected into a wound, the hydrogel forms a porous matrix in the tissue. Surface annealing locks in porosity and tissue grows into porous spaces, which avoids scar formation pathways and enables critical organs to regain function.

During in vivo tests, researchers observed decreases in inflammation compared with traditional hydrogels in the first 48 hours. “In mouse models, we found that if you inject in a hydrogel that has no porosity, the body tries to spit it out, and you have an immune reaction,” Dr. Scumpia said. “But when we used the MAP hydrogel, we found that cells can migrate through it, which allows wounds to heal quicker. When we added an antigen in the hydrogel trying to allow the hydrogel to degrade slower, it actually degraded more rapidly, but we found that new hair follicles formed in the center of these wounds, a hallmark of skin regeneration. My lab has been studying why this occurs and trying to use this to our advantage in other models.”

In an unpublished mouse burn wound model study, he and his colleagues excised a wound, but it never healed with regeneration in the center. “We don’t understand why,” he said. But when the researchers used the MAP gel in wounds of hairless mice, they observed the formation of sebaceous glands and hair follicles over the wound beds. “It’s an exciting finding to see hair follicles develop in the center of a wound,” Dr. Scumpia said. He noted that to date, use of the MAP hydrogel has demonstrated tissue regeneration in some of the 27 veterinary cases that have been performed, including for wounds following traumatic injuries or following tumor resections on paws that allowed the pets to avoid amputation.

Clinical trials planned

The first clinical trials of the MAP hydrogel are planned for treating complex diabetic wounds in early 2024 but will likely expand to other difficult-to-treat wounds, including venous stasis ulcers, decubitus ulcers, and use following large surgical resections. Dr. Scumpia and colleagues will also examine the regenerative biomaterial for tissue aesthetics, including dermal and deep tissue filler applications. The next steps in his laboratory, he said, are to combine biomaterials with stem cells, immune factors, or small molecular activators/inhibitors to improve sweat gland, nerve, or hair follicle regeneration.

Dr. Scumpia disclosed that he is a cofounder and shareholder in Tempo Therapeutics. He has also received grant support from the National Institutes of Health, Department of Veteran Affairs, and the LEO Foundation.