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New drugs in primary care: Lessons learned from COVID-19
SAN DIEGO – – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.
Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.
Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
Understanding the mechanism of action
Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.
“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.
“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.
Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.
Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.
Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.
When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.
Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.
“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.
Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
Effective in real world, but less so than in clinical trials
The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.
A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
Many drug-drug interactions, but they can be managed
Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.
To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.
This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.
To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:
- Prescribe an alternative COVID therapy.
- Temporarily withhold concomitant medication if clinically appropriate.
- Adjust the dose of concomitant medication and monitor for adverse effects.
Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
Important considerations
Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.
He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.
Dr. Smetana and Dr. Kiefl reported no disclosures.
SAN DIEGO – – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.
Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.
Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
Understanding the mechanism of action
Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.
“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.
“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.
Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.
Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.
Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.
When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.
Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.
“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.
Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
Effective in real world, but less so than in clinical trials
The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.
A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
Many drug-drug interactions, but they can be managed
Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.
To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.
This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.
To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:
- Prescribe an alternative COVID therapy.
- Temporarily withhold concomitant medication if clinically appropriate.
- Adjust the dose of concomitant medication and monitor for adverse effects.
Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
Important considerations
Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.
He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.
Dr. Smetana and Dr. Kiefl reported no disclosures.
SAN DIEGO – – plus it has helped keep many patients out of the hospital, according to a presenter at the annual meeting of the American College of Physicians.
Nirmatrelvir-ritonavir was granted emergency use authorization by the FDA late in 2021 to prevent progression to severe disease when COVID-19 cases and deaths were surging, and the Delta and Omicron variants started to spread.
Gerald Smetana, MD, an internist at Beth Israel Deaconess Medical Center in Boston, discussed nirmatrelvir-ritonavir as an example of how new drugs relevant to primary care can have a profound impact on public health.
Understanding the mechanism of action
Nirmatrelvir is the active agent of this combination and inhibits the SARS-CoV-2 main protease (Mpro), which is required for viral replication. In contrast to the SARS-CoV-2 spike protein, Mpro is highly conserved in coronaviruses and rarely acquires mutations. Therefore, unlike monoclonal antibodies targeting the spike protein, nirmatrelvir is active against known Omicron variants and is predicted to remain active against new variants that may emerge. The HIV1 protease inhibitor ritonavir has no activity against SARS-CoV-2. It can help increase the serum concentration of nirmatrelvir by inhibiting its metabolization.
“Although the details are not important for prescribing internists, having a basic understanding of the mechanism of action can help [doctors] better understand for which patients the drugs are indicated,” said Dr. Smetana, also a professor of medicine at Harvard Medical School, Boston. This is particularly important for newly approved drugs with a lot of new information to digest.
“Knowing the mechanisms of action of new drugs can help us predict their efficacy and potential side effects,” said Hubertus Kiefl, MD, an internist at Beth Israel Deaconess Medical Center and a lecturer at Harvard Medical School, during an interview after the session.
Understanding how drugs work also can help clinicians make better decisions, such as avoiding the use of a monoclonal antibody during a surge of a new variant with mutations in surface proteins or carefully managing the use of nirmatrelvir-ritonavir in patients who take certain medications that would cause potentially serious drug-drug interactions, Dr. Kiefl added.
Nirmatrelvir-ritonavir reduces the risk of hospitalization – but only in high-risk patients.
Dr. Smetana presented published data from the EPIC-HR study, a pivotal phase 2-3 clinical trial in 2,246 adult patients with COVID-19, all of whom were unvaccinated. Additionally, all patients had at least one risk factor for progression to severe disease.
When initiated 5 days after symptom onset or earlier, treatment with 300 mg nirmatrelvir plus 100 mg ritonavir twice a day for 5 days led to an 89% relative risk reduction in COVID-19–related hospitalization or death through day 28, compared with placebo.
Subgroup analyses showed that some patients benefited more than others. The highest risk reduction after treatment with nirmatrelvir-ritonavir was observed in patients at least 65 years old.
“It is important to remember that all the patients of this study were unvaccinated and [had] not had prior SARS-CoV-2 infection. This study population isn’t representative of most patients we are seeing today,” said Dr. Smetana.
Unpublished data from a study of standard-risk patients showed a nonsignificant reduction in the risk of hospitalization or death, he said. The study was stopped because of the low rates of hospitalization and death.
Effective in real world, but less so than in clinical trials
The fact that the patient cohort in the EPIC-HR trial was different from the patients internists see today makes real-world data critical for determining the usefulness of nirmatrelvir-ritonavir in everyday practice, Dr. Smetana said.
A real-world study from Israel conducted during the first Omicron wave (January to March 2022) showed that treatment with nirmatrelvir alone substantially reduced the relative risk of hospitalization in adults older than 65, with no evidence of benefit in adults aged 40-65. Dr. Smetana highlighted that, unlike the EPIC-HR cohort, most patients in the Israeli study had prior immunity due to vaccination or prior SARS-CoV-2 infection.
Many drug-drug interactions, but they can be managed
Nirmatrelvir-ritonavir interacts with many drugs, some of which are commonly used by primary care patients.
To help internists identify drug-drug interactions, Dr. Smetana proposed the use of the Liverpool COVID-19 Drug Interactions Checker, an intuitive tool that can help prescribers identify potential drug-drug interactions, categorize them based on severity, and identify management strategies.
This tool is specific to COVID-19 drugs. The Liverpool group also offers online drug interaction checkers for HIV, hepatitis, and cancer. “We need more tools like this to help improve the safe use of new drugs,” Dr. Smetana said.
To manage drug interactions, according to Dr. Smetana, U.S. treatment guidelines offer the following three options:
- Prescribe an alternative COVID therapy.
- Temporarily withhold concomitant medication if clinically appropriate.
- Adjust the dose of concomitant medication and monitor for adverse effects.
Medication doses that are withheld or modified should be continued through 3 days after completing nirmatrelvir-ritonavir, he added.
Important considerations
Commenting on things to consider for patients with COVID-19, Dr. Smetana said that there is a short window after symptom onset when nirmatrelvir-ritonavir can be prescribed, and safety in pregnancy is not known. There is also uncertainty regarding funding of nirmatrelvir-ritonavir prescriptions after the state of emergency is lifted. He reminded attendees that, although nirmatrelvir-ritonavir is the preferred first-line treatment for high-risk patients, another antiviral agent, molnupiravir, is also available and might be more appropriate for some patients.
He also cautioned about prescribing new drugs off label for indications that are not yet FDA-approved. “We are often stewards of limited resources when new drugs first become available but are not yet in sufficient supply to meet demand. Limiting our prescribing to FDA-approved indications helps to ensure equitable access,” he said.
Dr. Smetana and Dr. Kiefl reported no disclosures.
AT INTERNAL MEDICINE 2023
Panel backs limited new olaparib use in prostate cancer
A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.
On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.
Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.
In reviewing the application, a phrase agency staff used in their briefing document.
Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”
The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.
Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.
The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).
Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.
In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.
That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.
Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.
The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.
Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.
AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”
One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.
People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.
But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.
“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.
A version of this article first appeared on Medscape.com.
A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.
On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.
Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.
In reviewing the application, a phrase agency staff used in their briefing document.
Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”
The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.
Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.
The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).
Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.
In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.
That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.
Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.
The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.
Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.
AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”
One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.
People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.
But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.
“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.
A version of this article first appeared on Medscape.com.
A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.
On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.
Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.
In reviewing the application, a phrase agency staff used in their briefing document.
Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”
The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.
Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.
The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).
Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.
In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.
That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.
Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.
The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.
Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.
AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”
One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.
People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.
But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.
“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.
A version of this article first appeared on Medscape.com.
FDA expands atogepant approval to include chronic migraine
The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.
The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.
Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.
The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.
The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.
Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.
The efficacy results are consistent with those in the ADVANCE episodic migraine trial.
The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.
“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.
The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.
A version of this article originally appeared on Medscape.com.
The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.
The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.
Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.
The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.
The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.
Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.
The efficacy results are consistent with those in the ADVANCE episodic migraine trial.
The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.
“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.
The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.
A version of this article originally appeared on Medscape.com.
The approval makes atogepant the first, and only, oral calcitonin gene-related peptide receptor antagonist approved to prevent migraine across frequencies, including episodic and chronic, the company said in a news release.
The FDA initially approved atogepant in 2021 for the prevention of episodic migraine in adults.
Once-daily atogepant is available in three doses – 10 mg, 30 mg, and 60 mg – for prevention of episodic migraine. However, only the 60-mg dose of medication is indicated for the preventive treatment of chronic migraine.
The expanded indication in chronic migraine is based on positive results of the phase 3 PROGRESS trial, which evaluated atogepant in more than 700 adults with chronic migraine.
The trial met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days with atogepant compared with placebo across the 12-week treatment period.
Treatment with atogepant also led to statistically significant improvements in all six secondary endpoints, including the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across 12 weeks and improvements in function and reduction in activity impairment caused by migraine.
The efficacy results are consistent with those in the ADVANCE episodic migraine trial.
The overall safety profile of atogepant is consistent with the episodic migraine patient population, with the most common adverse events including constipation, nausea, and fatigue/sleepiness.
“The FDA approval is an important milestone, providing those most impacted by migraine with a new, safe, and effective treatment option in a convenient, once-daily pill,” Peter McAllister, MD, director of the New England Center for Neurology and Headache, Stamford, Conn., said in the news release.
The data demonstrate that atogepant “helps reduce the burden of migraine by delivering improvements in function, with high response rates and sustained efficacy over 12 weeks. These are critical factors neurologists and headache specialists consider when prescribing a treatment option, particularly for those with chronic migraine,” Dr. McAllister added.
A version of this article originally appeared on Medscape.com.
FMT in a pill: FDA approves second product to prevent C. diff recurrence
The recent approval of the first oral fecal-derived microbiota therapy to prevent the recurrence of Clostridioides difficile (C. diff) infection in patients was welcome news for physicians who’ve struggled under the weight of having too few treatment options for the prevention of C. diff recurrence.
The product, developed by Massachusetts-based Seres Therepeutics and marketed as Vowst, was approved by the U.S. Food and Drug Administration on April 26. It is approved for use in adults who have already been treated with antibiotics for a recurrent infection with C. diff bacteria.
and is designed to be delivered in four capsules taken daily for 3 days.
Gastroenterologist Phillip I. Tarr, MD, division chief of gastroenterology at Washington University, St. Louis, and chair of the American Gastroenterological Association Center for Gut Microbiome Research and Education, said that prevention of recurrent C. diff infection “remains challenging,” and that Vowst “provides the first FDA-approved, orally administered microbiome therapeutic with which to achieve this goal. This advance also makes us optimistic we might soon be able to prevent other disorders by managing gut microbial communities.”
Vowst is the second therapy derived from human stool to be approved for the indication in less than 6 months. In December, the FDA approved Rebyota (Ferring), a rectally delivered treatment that also uses microbes from donor feces. Both products were given priority review, orphan drug, and breakthrough therapy designations by the agency.
C. diff infection can be aggravated by an alteration of normal gut flora associated with antibiotics treatment, leading to cycles of repeated infections. Infection can produce diarrhea, abdominal pain, fever, and severe morbidity. In the United States, an estimated 15,000 to 30,000 deaths per year are linked to C. diff. Risk factors for recurrent infection include being 65 or older, hospitalization, being in a nursing home, a weakened immune system, and previous infection with C. diff.
Therapies transplanting fecal microbiota from donors have been used since the 1950s as treatments for recurrent C. diff infection, and in the past decade, as stool banks recruiting screened donors have made fecal microbiota transplants, or FMT, standard of care. However, only in recent years have fecal-derived therapies become subject to standardized safety and efficacy testing.
Both the current FDA-approved products, Rebyota and Vowst, were shown in randomized controlled trials to reduce recurrence of C. diff infection, compared with placebo. In a phase 3 clinical trial of Rebyota (n = 262) in antibiotic-treated patients, one rectally administered dose reduced recurrence of C. diff infection by 70.6% at 8 weeks, compared with 57.5% for placebo. A phase 3 study of Vowst (n = 281) showed recurrence in treated subjects to be 12.4% at 8 weeks, compared with nearly 40% of those receiving placebo (relative risk, 0.32; 95% confidence interval, 0.18-0.58; P less than .001).
Despite screening protocols that have become increasingly homogenized and rigorous, FMT is associated with the risk of introducing pathogens. Vowst is manufactured with purified bacterial spores derived from donor feces, not whole stool. Nonetheless, FDA noted in its statement that Vowst could still potentially introduce infectious agents or allergens.
Antibiotics are still first-line treatment
In an interview, Jessica Allegretti, MD, MPH, AGAF, medical director of the Crohn’s and Colitis Center at Brigham & Women’s Hospital, Boston, said that having two FDA-approved therapies with different means of administration “is great for the field and great for patients. These are both meant to be used after a course of antibiotics, so antibiotics are still the mainstay of treatment for C. diff and recurrent C. diff, but we now have more options to prevent recurrence.”
The convenience of an oral therapy that can be taken at home is “very attractive,” Dr. Allegretti added, noting that there will also be patients “who either don’t want to or can’t take capsules, for whom a rectal administration [in a health care setting] may be preferred.”
Dr. Allegretti, who has used FMT to treat recurrent C. difficile for more than a decade, said that she expected traditional FMT using screened donor stool to remain available even as the new products are adopted by clinicians. FMT centers like OpenBiome “will continue to provide access for patients who either don’t have the ability to get the FDA-approved products because of insurance coverage, or for financial reasons, or maybe neither of the new products is appropriate for them,” she said. “I do think there will always be a need for the traditional option. The more options that we have available the better.”
TD Cowen analyst Joseph Thome told Reuters that the drug could be priced close to $20,000 per course, expecting peak sales of $750 million in the U.S. in 2033.
Dr. Allegretti disclosed consulting work for Seres Therapeutics, Ferring, and other manufacturers. She is a member of OpenBiome’s clinical advisory board.
The recent approval of the first oral fecal-derived microbiota therapy to prevent the recurrence of Clostridioides difficile (C. diff) infection in patients was welcome news for physicians who’ve struggled under the weight of having too few treatment options for the prevention of C. diff recurrence.
The product, developed by Massachusetts-based Seres Therepeutics and marketed as Vowst, was approved by the U.S. Food and Drug Administration on April 26. It is approved for use in adults who have already been treated with antibiotics for a recurrent infection with C. diff bacteria.
and is designed to be delivered in four capsules taken daily for 3 days.
Gastroenterologist Phillip I. Tarr, MD, division chief of gastroenterology at Washington University, St. Louis, and chair of the American Gastroenterological Association Center for Gut Microbiome Research and Education, said that prevention of recurrent C. diff infection “remains challenging,” and that Vowst “provides the first FDA-approved, orally administered microbiome therapeutic with which to achieve this goal. This advance also makes us optimistic we might soon be able to prevent other disorders by managing gut microbial communities.”
Vowst is the second therapy derived from human stool to be approved for the indication in less than 6 months. In December, the FDA approved Rebyota (Ferring), a rectally delivered treatment that also uses microbes from donor feces. Both products were given priority review, orphan drug, and breakthrough therapy designations by the agency.
C. diff infection can be aggravated by an alteration of normal gut flora associated with antibiotics treatment, leading to cycles of repeated infections. Infection can produce diarrhea, abdominal pain, fever, and severe morbidity. In the United States, an estimated 15,000 to 30,000 deaths per year are linked to C. diff. Risk factors for recurrent infection include being 65 or older, hospitalization, being in a nursing home, a weakened immune system, and previous infection with C. diff.
Therapies transplanting fecal microbiota from donors have been used since the 1950s as treatments for recurrent C. diff infection, and in the past decade, as stool banks recruiting screened donors have made fecal microbiota transplants, or FMT, standard of care. However, only in recent years have fecal-derived therapies become subject to standardized safety and efficacy testing.
Both the current FDA-approved products, Rebyota and Vowst, were shown in randomized controlled trials to reduce recurrence of C. diff infection, compared with placebo. In a phase 3 clinical trial of Rebyota (n = 262) in antibiotic-treated patients, one rectally administered dose reduced recurrence of C. diff infection by 70.6% at 8 weeks, compared with 57.5% for placebo. A phase 3 study of Vowst (n = 281) showed recurrence in treated subjects to be 12.4% at 8 weeks, compared with nearly 40% of those receiving placebo (relative risk, 0.32; 95% confidence interval, 0.18-0.58; P less than .001).
Despite screening protocols that have become increasingly homogenized and rigorous, FMT is associated with the risk of introducing pathogens. Vowst is manufactured with purified bacterial spores derived from donor feces, not whole stool. Nonetheless, FDA noted in its statement that Vowst could still potentially introduce infectious agents or allergens.
Antibiotics are still first-line treatment
In an interview, Jessica Allegretti, MD, MPH, AGAF, medical director of the Crohn’s and Colitis Center at Brigham & Women’s Hospital, Boston, said that having two FDA-approved therapies with different means of administration “is great for the field and great for patients. These are both meant to be used after a course of antibiotics, so antibiotics are still the mainstay of treatment for C. diff and recurrent C. diff, but we now have more options to prevent recurrence.”
The convenience of an oral therapy that can be taken at home is “very attractive,” Dr. Allegretti added, noting that there will also be patients “who either don’t want to or can’t take capsules, for whom a rectal administration [in a health care setting] may be preferred.”
Dr. Allegretti, who has used FMT to treat recurrent C. difficile for more than a decade, said that she expected traditional FMT using screened donor stool to remain available even as the new products are adopted by clinicians. FMT centers like OpenBiome “will continue to provide access for patients who either don’t have the ability to get the FDA-approved products because of insurance coverage, or for financial reasons, or maybe neither of the new products is appropriate for them,” she said. “I do think there will always be a need for the traditional option. The more options that we have available the better.”
TD Cowen analyst Joseph Thome told Reuters that the drug could be priced close to $20,000 per course, expecting peak sales of $750 million in the U.S. in 2033.
Dr. Allegretti disclosed consulting work for Seres Therapeutics, Ferring, and other manufacturers. She is a member of OpenBiome’s clinical advisory board.
The recent approval of the first oral fecal-derived microbiota therapy to prevent the recurrence of Clostridioides difficile (C. diff) infection in patients was welcome news for physicians who’ve struggled under the weight of having too few treatment options for the prevention of C. diff recurrence.
The product, developed by Massachusetts-based Seres Therepeutics and marketed as Vowst, was approved by the U.S. Food and Drug Administration on April 26. It is approved for use in adults who have already been treated with antibiotics for a recurrent infection with C. diff bacteria.
and is designed to be delivered in four capsules taken daily for 3 days.
Gastroenterologist Phillip I. Tarr, MD, division chief of gastroenterology at Washington University, St. Louis, and chair of the American Gastroenterological Association Center for Gut Microbiome Research and Education, said that prevention of recurrent C. diff infection “remains challenging,” and that Vowst “provides the first FDA-approved, orally administered microbiome therapeutic with which to achieve this goal. This advance also makes us optimistic we might soon be able to prevent other disorders by managing gut microbial communities.”
Vowst is the second therapy derived from human stool to be approved for the indication in less than 6 months. In December, the FDA approved Rebyota (Ferring), a rectally delivered treatment that also uses microbes from donor feces. Both products were given priority review, orphan drug, and breakthrough therapy designations by the agency.
C. diff infection can be aggravated by an alteration of normal gut flora associated with antibiotics treatment, leading to cycles of repeated infections. Infection can produce diarrhea, abdominal pain, fever, and severe morbidity. In the United States, an estimated 15,000 to 30,000 deaths per year are linked to C. diff. Risk factors for recurrent infection include being 65 or older, hospitalization, being in a nursing home, a weakened immune system, and previous infection with C. diff.
Therapies transplanting fecal microbiota from donors have been used since the 1950s as treatments for recurrent C. diff infection, and in the past decade, as stool banks recruiting screened donors have made fecal microbiota transplants, or FMT, standard of care. However, only in recent years have fecal-derived therapies become subject to standardized safety and efficacy testing.
Both the current FDA-approved products, Rebyota and Vowst, were shown in randomized controlled trials to reduce recurrence of C. diff infection, compared with placebo. In a phase 3 clinical trial of Rebyota (n = 262) in antibiotic-treated patients, one rectally administered dose reduced recurrence of C. diff infection by 70.6% at 8 weeks, compared with 57.5% for placebo. A phase 3 study of Vowst (n = 281) showed recurrence in treated subjects to be 12.4% at 8 weeks, compared with nearly 40% of those receiving placebo (relative risk, 0.32; 95% confidence interval, 0.18-0.58; P less than .001).
Despite screening protocols that have become increasingly homogenized and rigorous, FMT is associated with the risk of introducing pathogens. Vowst is manufactured with purified bacterial spores derived from donor feces, not whole stool. Nonetheless, FDA noted in its statement that Vowst could still potentially introduce infectious agents or allergens.
Antibiotics are still first-line treatment
In an interview, Jessica Allegretti, MD, MPH, AGAF, medical director of the Crohn’s and Colitis Center at Brigham & Women’s Hospital, Boston, said that having two FDA-approved therapies with different means of administration “is great for the field and great for patients. These are both meant to be used after a course of antibiotics, so antibiotics are still the mainstay of treatment for C. diff and recurrent C. diff, but we now have more options to prevent recurrence.”
The convenience of an oral therapy that can be taken at home is “very attractive,” Dr. Allegretti added, noting that there will also be patients “who either don’t want to or can’t take capsules, for whom a rectal administration [in a health care setting] may be preferred.”
Dr. Allegretti, who has used FMT to treat recurrent C. difficile for more than a decade, said that she expected traditional FMT using screened donor stool to remain available even as the new products are adopted by clinicians. FMT centers like OpenBiome “will continue to provide access for patients who either don’t have the ability to get the FDA-approved products because of insurance coverage, or for financial reasons, or maybe neither of the new products is appropriate for them,” she said. “I do think there will always be a need for the traditional option. The more options that we have available the better.”
TD Cowen analyst Joseph Thome told Reuters that the drug could be priced close to $20,000 per course, expecting peak sales of $750 million in the U.S. in 2033.
Dr. Allegretti disclosed consulting work for Seres Therapeutics, Ferring, and other manufacturers. She is a member of OpenBiome’s clinical advisory board.
FDA gives fast-track approval to new ALS drug
the debilitating and deadly disease for which there is no cure.
Most people with ALS die within 3-5 years of when symptoms appear, usually of respiratory failure.
The newly approved drug, called Qalsody, is made by the Swiss company Biogen. The FDA fast-tracked the approval based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.
While the drug was shown to impact the chemical process in the body linked to degeneration, there was no significant change in people’s symptoms during the first 28 weeks that they took the drug, Biogen said in a news release. But the company noted that some patients did see improved functioning after starting treatment.
“I have observed the positive impact Qalsody has on slowing the progression of ALS in people with SOD1 mutations,” Timothy M. Miller, MD, PhD, researcher and codirector of the ALS Center at Washington University in St. Louis, said in a statement released by Biogen. “The FDA’s approval of Qalsody gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”
Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.
The new treatment is approved only for people with a rare kind of ALS called SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.
In trials, 147 people received either Qalsody or a placebo, and the treatment significantly reduced the level of a protein in people’s blood that is associated with the loss of control of voluntary muscles.
Because Qalsody received a fast-track approval from the FDA, it must still provide more research data in the future, including from a trial examining how the drug affects people who carry the SOD1 gene but do not yet show symptoms of ALS.
A version of this article first appeared on Medscape.com.
the debilitating and deadly disease for which there is no cure.
Most people with ALS die within 3-5 years of when symptoms appear, usually of respiratory failure.
The newly approved drug, called Qalsody, is made by the Swiss company Biogen. The FDA fast-tracked the approval based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.
While the drug was shown to impact the chemical process in the body linked to degeneration, there was no significant change in people’s symptoms during the first 28 weeks that they took the drug, Biogen said in a news release. But the company noted that some patients did see improved functioning after starting treatment.
“I have observed the positive impact Qalsody has on slowing the progression of ALS in people with SOD1 mutations,” Timothy M. Miller, MD, PhD, researcher and codirector of the ALS Center at Washington University in St. Louis, said in a statement released by Biogen. “The FDA’s approval of Qalsody gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”
Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.
The new treatment is approved only for people with a rare kind of ALS called SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.
In trials, 147 people received either Qalsody or a placebo, and the treatment significantly reduced the level of a protein in people’s blood that is associated with the loss of control of voluntary muscles.
Because Qalsody received a fast-track approval from the FDA, it must still provide more research data in the future, including from a trial examining how the drug affects people who carry the SOD1 gene but do not yet show symptoms of ALS.
A version of this article first appeared on Medscape.com.
the debilitating and deadly disease for which there is no cure.
Most people with ALS die within 3-5 years of when symptoms appear, usually of respiratory failure.
The newly approved drug, called Qalsody, is made by the Swiss company Biogen. The FDA fast-tracked the approval based on early trial results. The agency said in a news release that its decision was based on the demonstrated ability of the drug to reduce a protein in the blood that is a sign of degeneration of brain and nerve cells.
While the drug was shown to impact the chemical process in the body linked to degeneration, there was no significant change in people’s symptoms during the first 28 weeks that they took the drug, Biogen said in a news release. But the company noted that some patients did see improved functioning after starting treatment.
“I have observed the positive impact Qalsody has on slowing the progression of ALS in people with SOD1 mutations,” Timothy M. Miller, MD, PhD, researcher and codirector of the ALS Center at Washington University in St. Louis, said in a statement released by Biogen. “The FDA’s approval of Qalsody gives me hope that people living with this rare form of ALS could experience a reduction in decline in strength, clinical function, and respiratory function.”
Qalsody is given to people via a spinal injection, with an initial course of three injections every 2 weeks. People then get the injection once every 28 days.
The new treatment is approved only for people with a rare kind of ALS called SOD1-ALS, which is known for a genetic mutation. While ALS affects up to 32,000 people in the United States, just 2% of people with ALS have the SOD1 gene mutation. The FDA says the number of people in the United States who could use Qalsody is about 500.
In trials, 147 people received either Qalsody or a placebo, and the treatment significantly reduced the level of a protein in people’s blood that is associated with the loss of control of voluntary muscles.
Because Qalsody received a fast-track approval from the FDA, it must still provide more research data in the future, including from a trial examining how the drug affects people who carry the SOD1 gene but do not yet show symptoms of ALS.
A version of this article first appeared on Medscape.com.
FDA okays latest artificial pancreas, the MiniMed 780G
The Food and Drug Administration has approved Medtronic Minimed’s 780G automated insulin delivery system with the Guardian 4 sensor.
The latest so-called artificial pancreas system is approved for people aged 7 years and older who have type 1 diabetes. Medtronic will begin taking preorders for the 780G on May 15, 2023. Users of the current MiniMed 770G will be eligible for no-cost remote software upgrades.
The 780G is currently available in 105 countries. It has been available in Europe since 2020 and in the United Kingdom since 2021. It is the first automated insulin delivery system to automatically administer bolus correction insulin doses every 5 minutes to correct meal-related hyperglycemia.
This so-called meal detection technology doesn’t replace manual premeal boluses but does provide extra insulin if the premeal bolus is skipped or is insufficient.
As with other automated systems, the 780G automatically adjusts basal insulin doses up or down based on glucose levels and trends and shuts off insulin delivery to prevent hypoglycemia. The insulin pump’s infusion set can be worn for 7 days, rather than 3 days as with the older system, and the glucose target level can be set as low as 100 mg/dL.
And in contrast to the older MiniMed 670G system, which tended to frequently boot users out of automated mode, with the 780G, users spent an average of 95% of the time in the automated “SmartGuard” mode.
In the pivotal U.S. trial, overall, patients who used the 780G spent 75% of the time in ideal glucose range (70-180 mg/dL) and 1.8% of the time below that range. Overnight, the figures were 82% and 1.5%, respectively. With the glucose target set at 100 mg/dL and active insulin time set to 2 hours, patients spent 78.8% of time in range without increased hyperglycemia.
In the ADAPT study, with the 780G, there was a 26% increase in time in ideal glucose range and a 1.4% reduction in A1c compared with results for patients who received multiple daily insulin injections with intermittently scanned continuous glucose monitoring, without an increase in hypoglycemia. Overnight, time in range increased 30.2%. The results were sustained at 1 year.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved Medtronic Minimed’s 780G automated insulin delivery system with the Guardian 4 sensor.
The latest so-called artificial pancreas system is approved for people aged 7 years and older who have type 1 diabetes. Medtronic will begin taking preorders for the 780G on May 15, 2023. Users of the current MiniMed 770G will be eligible for no-cost remote software upgrades.
The 780G is currently available in 105 countries. It has been available in Europe since 2020 and in the United Kingdom since 2021. It is the first automated insulin delivery system to automatically administer bolus correction insulin doses every 5 minutes to correct meal-related hyperglycemia.
This so-called meal detection technology doesn’t replace manual premeal boluses but does provide extra insulin if the premeal bolus is skipped or is insufficient.
As with other automated systems, the 780G automatically adjusts basal insulin doses up or down based on glucose levels and trends and shuts off insulin delivery to prevent hypoglycemia. The insulin pump’s infusion set can be worn for 7 days, rather than 3 days as with the older system, and the glucose target level can be set as low as 100 mg/dL.
And in contrast to the older MiniMed 670G system, which tended to frequently boot users out of automated mode, with the 780G, users spent an average of 95% of the time in the automated “SmartGuard” mode.
In the pivotal U.S. trial, overall, patients who used the 780G spent 75% of the time in ideal glucose range (70-180 mg/dL) and 1.8% of the time below that range. Overnight, the figures were 82% and 1.5%, respectively. With the glucose target set at 100 mg/dL and active insulin time set to 2 hours, patients spent 78.8% of time in range without increased hyperglycemia.
In the ADAPT study, with the 780G, there was a 26% increase in time in ideal glucose range and a 1.4% reduction in A1c compared with results for patients who received multiple daily insulin injections with intermittently scanned continuous glucose monitoring, without an increase in hypoglycemia. Overnight, time in range increased 30.2%. The results were sustained at 1 year.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved Medtronic Minimed’s 780G automated insulin delivery system with the Guardian 4 sensor.
The latest so-called artificial pancreas system is approved for people aged 7 years and older who have type 1 diabetes. Medtronic will begin taking preorders for the 780G on May 15, 2023. Users of the current MiniMed 770G will be eligible for no-cost remote software upgrades.
The 780G is currently available in 105 countries. It has been available in Europe since 2020 and in the United Kingdom since 2021. It is the first automated insulin delivery system to automatically administer bolus correction insulin doses every 5 minutes to correct meal-related hyperglycemia.
This so-called meal detection technology doesn’t replace manual premeal boluses but does provide extra insulin if the premeal bolus is skipped or is insufficient.
As with other automated systems, the 780G automatically adjusts basal insulin doses up or down based on glucose levels and trends and shuts off insulin delivery to prevent hypoglycemia. The insulin pump’s infusion set can be worn for 7 days, rather than 3 days as with the older system, and the glucose target level can be set as low as 100 mg/dL.
And in contrast to the older MiniMed 670G system, which tended to frequently boot users out of automated mode, with the 780G, users spent an average of 95% of the time in the automated “SmartGuard” mode.
In the pivotal U.S. trial, overall, patients who used the 780G spent 75% of the time in ideal glucose range (70-180 mg/dL) and 1.8% of the time below that range. Overnight, the figures were 82% and 1.5%, respectively. With the glucose target set at 100 mg/dL and active insulin time set to 2 hours, patients spent 78.8% of time in range without increased hyperglycemia.
In the ADAPT study, with the 780G, there was a 26% increase in time in ideal glucose range and a 1.4% reduction in A1c compared with results for patients who received multiple daily insulin injections with intermittently scanned continuous glucose monitoring, without an increase in hypoglycemia. Overnight, time in range increased 30.2%. The results were sustained at 1 year.
A version of this article first appeared on Medscape.com.
Perinatal HIV nearly eradicated in U.S.
, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.
The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.
Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.
Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.
“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.
The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.
“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said.
Disparities persist
But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”
Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.
Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.
Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.
They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.
“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
Progress in ‘danger’
Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.
Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.
“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.
In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.
“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”
A version of this article first appeared on Medscape.com.
, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.
The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.
Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.
Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.
“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.
The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.
“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said.
Disparities persist
But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”
Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.
Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.
Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.
They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.
“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
Progress in ‘danger’
Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.
Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.
“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.
In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.
“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”
A version of this article first appeared on Medscape.com.
, with less than 1 baby for every 100,000 live births having the virus, a new study released by researchers at the Centers for Disease Control and Prevention finds.
The report marks significant progress on the U.S. government’s goal to eradicate perinatal HIV, an immune-weakening and potentially deadly virus that is passed from mother to baby during pregnancy. Just 32 children in the country were diagnosed in 2019, compared with twice as many in 2010, according to the CDC.
Mothers who are HIV positive can prevent transmission of the infection by receiving antiretroviral therapy, according to Monica Gandhi, MD, MPH, a professor of medicine at University of California, San Francisco’s division of HIV, infectious disease and global medicine.
Dr. Gandhi said she could recall only one case of perinatal HIV in the San Francisco area over the last decade.
“This country has been really aggressive about counseling women who are pregnant and getting mothers in care,” Dr. Gandhi said.
The treatment method was discovered more than 30 years ago. Prior to the therapy and ensuing awareness campaigns to prevent transmission, mothers with HIV would typically pass the virus to their child in utero, during delivery, or while breastfeeding.
“There should be zero children born with HIV, given that we’ve had these drugs for so long,” Dr. Ghandi said.
Disparities persist
But challenges remain in some communities, where babies born to Black mothers are disproportionately affected by the disease, the new study found. “Racial and ethnic differences in perinatal HIV diagnoses persisted through the 10-year period,” the report’s authors concluded. “The highest rates of perinatal HIV diagnoses were seen among infants born to Black women.”
Although rates of perinatal HIV declined for babies born to Black mothers over the decade-long study, the diagnosis rate was above the goal of elimination at 3.1 for every 100,000 live births, according to the data.
Meanwhile, transmission rates hovered around 1%-2% for Latinx and Hispanic women and mothers who identified as “other races,” including Native American.
Despite the availability of medication, expectant mothers may face several hurdles to getting the daily treatment they need to prevent transmission to their fetus, according to Jennifer Jao, MD, MPH, a physician of infectious diseases at Lurie Children’s Hospital of Chicago.
They might have trouble securing health insurance or finding transportation to doctor’s appointments, or face other problems like lacking secure housing or food – all factors that prevent them from prioritizing the care.
“All of those things play into the mix,” Dr. Jao said. “We see over and over again that closing the gap means you’ve got to reach the women who are pregnant and who don’t have resources.”
Progress in ‘danger’
Experts said they’re not sure what the impact of the COVID-19 pandemic, accompanied by a recent uptick in sexually transmitted diseases, will be on rates of perinatal HIV. Some women were unable to access prenatal health care during the pandemic because they couldn’t access public transportation or childcare, the U.S. Government Accountability Office said in 2022.
Globally, a decline in rates of HIV and AIDS rates has slowed, prompting the World Health Organization to warn last year that progress on the disease is in danger. Researchers only included HIV rates in the United States through 2019, so the data are outdated, Dr. Gandhi noted.
“All of this put together means we don’t know where we are with perinatal transmission over the last 3 years,” she said.
In an accompanying editorial, coauthors Nahida Chakhtoura, MD, MsGH, and Bill Kapogiannis, MD, both with the National Institutes of Health, urge health care professionals to take an active role in eliminating these racial and ethnic disparities in an effort to – as the title of their editorial proclaims – achieve a “road to zero perinatal HIV transmission” in the United States.
“The more proactive we are in identifying and promptly addressing systematic deficiencies that exacerbate health inequities in cutting-edge research innovations and optimal clinical service provision,” they write, “the less reactive we will need to be when new transmissible infections appear at our doorstep.”
A version of this article first appeared on Medscape.com.
FDA OKs stem cell therapy for blood cancer patients to reduce infection risks
Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B3, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.
The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.
The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.
The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.
The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.
Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”
The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).
Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.
Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.
A version of this article originally appeared on Medscape.com.
Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B3, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.
The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.
The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.
The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.
The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.
Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”
The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).
Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.
Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.
A version of this article originally appeared on Medscape.com.
Omidubicel is made from umbilical cord donor stem cells that are processed with nicotinamide, a form of vitamin B3, to enhance and expand the number of progenitor cells, the product’s maker, Jerusalem-based Gamida Cell, explained in a press announcement.
The FDA approval was based on phase 3 testing that pitted the use of omidubicel in 62 patients against standard unmanipulated cord blood transplants in 63 patients following myeloablative conditioning.
The median time to neutrophil recovery was 12 days in the omidubicel group, compared with 22 days with standard care. Overall, 87% of patients who received omidubicel achieved neutrophil recovery versus 83% of patients with standard transplants.
The incidence of grade 2/3 bacterial or grade 3 fungal infections 100 days following transplant was 39% with omidubicel versus 60% with standard transplants.
The FDA’s “approval is an important advance in cell therapy treatment in patients with blood cancers. Hastening the return of the body’s white blood cells can reduce the possibility of serious or overwhelming infection associated with stem cell transplantation,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency press release.
Abbey Jenkins, president and CEO of Gamida, called the approval “a major advancement in the treatment of patients with hematologic malignancies that we believe may increase access to stem cell transplant and help improve patient outcomes.”
The most common grade 3–5 adverse reactions in the approval study were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).
Adverse events are consistent with allogeneic hematopoietic stem cell transplantation. Among 117 patients who received omidubicel for any indication, infusion reactions occurred in 47% of patients, acute graft-versus-host disease occurred in 58%, chronic GVHD occurred in 35%, and graft failure occurred in 3%. Labeling includes a boxed warning of the possibilities. There is also a small risk of infections and malignancies from donor blood.
Omidubicel is manufactured in Gamida’s facility in Kiryat Gat, Israel. It is available for order now and is expected to be delivered to transplant centers within 30 days after the start of manufacturing, the company said.
A version of this article originally appeared on Medscape.com.
FDA breakthrough designation for spinal cord stimulation device
The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.
“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.
“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.
Results of the first-in-human study of the system were published in Nature Medicine.
Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.
In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.
The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.
“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.
Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.
Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.
The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.
Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.
“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.
“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.
Results of the first-in-human study of the system were published in Nature Medicine.
Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.
In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.
The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.
“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.
Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.
Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.
The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.
Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has granted breakthrough device designation to the Avantis spinal cord stimulation system (Reach Neuro), which has been shown in early testing to restore arm and hand movement in patients with post-stroke upper limb paresis.
“We are excited about the FDA’s recognition of our technology’s potential to change the lives of millions of people living with disability,” Marc Powell, PhD, CEO, and co-founder of Reach Neuro, said in a company news release.
“The breakthrough device designation is an incredible opportunity to work closely with FDA experts to expedite the clinical translation of the Avantis system,” Dr. Powell added.
Results of the first-in-human study of the system were published in Nature Medicine.
Investigators percutaneously implanted two linear leads in the dorsolateral epidural space targeting neural circuits that control arm and hand muscles in two chronic post-stroke patients.
In both patients, continuous stimulation of the targeted neural circuits led to significant and immediate improvement in arm and hand strength and dexterity. This enabled the patients to perform movements that they couldn’t perform without spinal cord stimulation.
The process also enabled fine motor skills, such as opening a lock and using utensils to eat independently – tasks that one patient had not been able to do for 9 years.
“Having the stimulation working and being able to move my arm/hand again after 9 years was one of the most surreal experiences of my life – it was as if my brain was in control of my arm again. This technology gave me such immense hope that one day I will regain a sense of independence again,” study participant Heather Rendulic said in the news release.
Surprisingly, some improvements were retained up to 1 month after the study, even without stimulation. No serious adverse events were reported.
Nearly three-quarters of patients with stroke experience lasting deficits in motor control of their arm and hand as a result of permanent damage to the brain’s ability to send signals to muscles.
The early results with the Avantis system provide “promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke,” the study team said in Nature Medicine.
Reach Neuro was founded in 2021 as a spinout company of the University of Pittsburgh and Carnegie Mellon University, also in Pittsburgh, where the technology is currently being tested in a clinical trial funded by the National Institutes of Health.
A version of this article first appeared on Medscape.com.
U.S. syphilis cases reach 70-year high
Cases of the sexually transmitted disease syphilis soared in 2021 to the highest total in more than 70 years, a new report says.
Earlier in 2023, the Centers for Disease Control and Prevention issued preliminary projections that syphilis rates had made a startling jump from 2020 to 2021. But now that health officials have finalized all of the 2021 data, the increase is worse than what was announced back in March.
In just a 1-year period, from 2020 to 2021, cases increased by 32%, to 176,713, according to newly finalized data from the CDC. That is the highest total number of syphilis cases the U.S. has seen since 1950.
The total number of STD cases in the U.S. in 2021 was 2.5 million, including 1.6 million cases of chlamydia, which was up 4% over the year prior.
A CDC official labeled the situation an epidemic.
“The reasons for the ongoing increases are multifaceted – and so are the solutions,” said Leandro Mena, MD, MPH, director of the CDC’s STD prevention division, in a statement. “It will take many of us working together to effectively use new and existing tools to increase access to quality sexual health care services for more people and to encourage ongoing innovation and prioritization of STI prevention and treatment in this country.”
Syphilis causes sores and rashes and, left untreated over a long period of time, can cause severe problems in organs, the brain, and the nervous system. Untreated congenital syphilis can lead to stillbirth. The treatment for syphilis is antibiotics.
The CDC called a 32% increase from 2020 to 2021 of congenital syphilis cases “alarming,” reporting that it resulted in 220 stillbirths and infant deaths in 2021.
The rise in STDs during the pandemic has been attributed to decreased attention and resources devoted to sexual health. Opioid use is also considered a contributing factor.
A version of this article first appeared on WebMD.com.
Cases of the sexually transmitted disease syphilis soared in 2021 to the highest total in more than 70 years, a new report says.
Earlier in 2023, the Centers for Disease Control and Prevention issued preliminary projections that syphilis rates had made a startling jump from 2020 to 2021. But now that health officials have finalized all of the 2021 data, the increase is worse than what was announced back in March.
In just a 1-year period, from 2020 to 2021, cases increased by 32%, to 176,713, according to newly finalized data from the CDC. That is the highest total number of syphilis cases the U.S. has seen since 1950.
The total number of STD cases in the U.S. in 2021 was 2.5 million, including 1.6 million cases of chlamydia, which was up 4% over the year prior.
A CDC official labeled the situation an epidemic.
“The reasons for the ongoing increases are multifaceted – and so are the solutions,” said Leandro Mena, MD, MPH, director of the CDC’s STD prevention division, in a statement. “It will take many of us working together to effectively use new and existing tools to increase access to quality sexual health care services for more people and to encourage ongoing innovation and prioritization of STI prevention and treatment in this country.”
Syphilis causes sores and rashes and, left untreated over a long period of time, can cause severe problems in organs, the brain, and the nervous system. Untreated congenital syphilis can lead to stillbirth. The treatment for syphilis is antibiotics.
The CDC called a 32% increase from 2020 to 2021 of congenital syphilis cases “alarming,” reporting that it resulted in 220 stillbirths and infant deaths in 2021.
The rise in STDs during the pandemic has been attributed to decreased attention and resources devoted to sexual health. Opioid use is also considered a contributing factor.
A version of this article first appeared on WebMD.com.
Cases of the sexually transmitted disease syphilis soared in 2021 to the highest total in more than 70 years, a new report says.
Earlier in 2023, the Centers for Disease Control and Prevention issued preliminary projections that syphilis rates had made a startling jump from 2020 to 2021. But now that health officials have finalized all of the 2021 data, the increase is worse than what was announced back in March.
In just a 1-year period, from 2020 to 2021, cases increased by 32%, to 176,713, according to newly finalized data from the CDC. That is the highest total number of syphilis cases the U.S. has seen since 1950.
The total number of STD cases in the U.S. in 2021 was 2.5 million, including 1.6 million cases of chlamydia, which was up 4% over the year prior.
A CDC official labeled the situation an epidemic.
“The reasons for the ongoing increases are multifaceted – and so are the solutions,” said Leandro Mena, MD, MPH, director of the CDC’s STD prevention division, in a statement. “It will take many of us working together to effectively use new and existing tools to increase access to quality sexual health care services for more people and to encourage ongoing innovation and prioritization of STI prevention and treatment in this country.”
Syphilis causes sores and rashes and, left untreated over a long period of time, can cause severe problems in organs, the brain, and the nervous system. Untreated congenital syphilis can lead to stillbirth. The treatment for syphilis is antibiotics.
The CDC called a 32% increase from 2020 to 2021 of congenital syphilis cases “alarming,” reporting that it resulted in 220 stillbirths and infant deaths in 2021.
The rise in STDs during the pandemic has been attributed to decreased attention and resources devoted to sexual health. Opioid use is also considered a contributing factor.
A version of this article first appeared on WebMD.com.