Image from Ed Uthman

Prothena Corporation plc is discontinuing development of NEOD001, an investigational antibody intended for the treatment of AL amyloidosis.

The company’s decision was based on results from the phase 2b PRONTO study and a futility analysis of the phase 3 VITAL study.

NEOD001 did not meet the primary or secondary endpoints of the PRONTO study, so Prothena asked an independent data monitoring committee to review a futility analysis of the ongoing VITAL study.

The committee recommended discontinuation of the VITAL study, so Prothena decided to discontinue all development of NEOD001, including the VITAL study and open-label extension studies.

“We are deeply disappointed by this outcome, particularly for patients suffering from this devastating disease,” said Gene Kinney, PhD, president and chief executive officer of Prothena.

“We are surprised by the results from these 2 placebo-controlled studies and will continue to analyze the resulting data to share insights with our collaborators in the scientific, medical, and advocacy communities.”

Phase 3 VITAL study

The VITAL study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in treatment-naïve patients with AL amyloidosis and cardiac dysfunction.

The study enrolled 260 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 or placebo via intravenous infusion every 28 days. Patients in both arms received concurrent standard of care therapy.

The composite primary endpoint was event-based, with all-cause mortality or cardiac hospitalizations counted as events.

The futility analysis, based on 103 adjudicated events of the 156 events specified to complete the study, was not statistically significant. The hazard ratio was 0.84 favoring NEOD001 versus the control arm.

Phase 2b PRONTO study

The PRONTO study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in previously treated patients with AL amyloidosis and persistent cardiac dysfunction.

The study enrolled 129 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 (n=66) or placebo (n=63) via intravenous infusion every 28 days.

There was no significant difference between the treatment arms for any of the study’s endpoints.

The primary endpoint was cardiac best response, as assessed by N-terminal pro B-type natriuretic peptide (NT-proBNP) through 12 months of treatment. This endpoint was achieved by 39.4% of patients in the NEOD001 arm and 47.6% in the placebo arm.

The NT-proBNP rate of change (slope) through 12 months of treatment was 9.80 in the NEOD001 arm and 81.42 in the placebo arm.

The mean change in Short-form 36 Physical Component Summary Score after 12 months of treatment was 0.19 and 0.97, respectively.

The median change in 6-Minute Walk Test distance after 12 months of treatment was 19.25 m and 8.00 m, respectively.

And the mean change in Neuropathy Impairment Score of the Lower Limb after 12 months of treatment was -1.20 and -0.60, respectively.

The rate of renal best response (as assessed by proteinuria and estimated glomerular filtration rate) through 12 months of treatment was 53.8% in the NEOD001 arm and 33.3% in the placebo arm.

The rate of all-cause mortality was 4.5% (n=3) and 9.5% (n=6), respectively.

Prothena said NEOD001 was generally safe and well tolerated in this trial.

Image from Ed Uthman

Prothena Corporation plc is discontinuing development of NEOD001, an investigational antibody intended for the treatment of AL amyloidosis.

The company’s decision was based on results from the phase 2b PRONTO study and a futility analysis of the phase 3 VITAL study.

NEOD001 did not meet the primary or secondary endpoints of the PRONTO study, so Prothena asked an independent data monitoring committee to review a futility analysis of the ongoing VITAL study.

The committee recommended discontinuation of the VITAL study, so Prothena decided to discontinue all development of NEOD001, including the VITAL study and open-label extension studies.

“We are deeply disappointed by this outcome, particularly for patients suffering from this devastating disease,” said Gene Kinney, PhD, president and chief executive officer of Prothena.

“We are surprised by the results from these 2 placebo-controlled studies and will continue to analyze the resulting data to share insights with our collaborators in the scientific, medical, and advocacy communities.”

Phase 3 VITAL study

The VITAL study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in treatment-naïve patients with AL amyloidosis and cardiac dysfunction.

The study enrolled 260 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 or placebo via intravenous infusion every 28 days. Patients in both arms received concurrent standard of care therapy.

The composite primary endpoint was event-based, with all-cause mortality or cardiac hospitalizations counted as events.

The futility analysis, based on 103 adjudicated events of the 156 events specified to complete the study, was not statistically significant. The hazard ratio was 0.84 favoring NEOD001 versus the control arm.

Phase 2b PRONTO study

The PRONTO study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in previously treated patients with AL amyloidosis and persistent cardiac dysfunction.

The study enrolled 129 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 (n=66) or placebo (n=63) via intravenous infusion every 28 days.

There was no significant difference between the treatment arms for any of the study’s endpoints.

The primary endpoint was cardiac best response, as assessed by N-terminal pro B-type natriuretic peptide (NT-proBNP) through 12 months of treatment. This endpoint was achieved by 39.4% of patients in the NEOD001 arm and 47.6% in the placebo arm.

The NT-proBNP rate of change (slope) through 12 months of treatment was 9.80 in the NEOD001 arm and 81.42 in the placebo arm.

The mean change in Short-form 36 Physical Component Summary Score after 12 months of treatment was 0.19 and 0.97, respectively.

The median change in 6-Minute Walk Test distance after 12 months of treatment was 19.25 m and 8.00 m, respectively.

And the mean change in Neuropathy Impairment Score of the Lower Limb after 12 months of treatment was -1.20 and -0.60, respectively.

The rate of renal best response (as assessed by proteinuria and estimated glomerular filtration rate) through 12 months of treatment was 53.8% in the NEOD001 arm and 33.3% in the placebo arm.

The rate of all-cause mortality was 4.5% (n=3) and 9.5% (n=6), respectively.

Prothena said NEOD001 was generally safe and well tolerated in this trial.

Image from Ed Uthman

Prothena Corporation plc is discontinuing development of NEOD001, an investigational antibody intended for the treatment of AL amyloidosis.

The company’s decision was based on results from the phase 2b PRONTO study and a futility analysis of the phase 3 VITAL study.

NEOD001 did not meet the primary or secondary endpoints of the PRONTO study, so Prothena asked an independent data monitoring committee to review a futility analysis of the ongoing VITAL study.

The committee recommended discontinuation of the VITAL study, so Prothena decided to discontinue all development of NEOD001, including the VITAL study and open-label extension studies.

“We are deeply disappointed by this outcome, particularly for patients suffering from this devastating disease,” said Gene Kinney, PhD, president and chief executive officer of Prothena.

“We are surprised by the results from these 2 placebo-controlled studies and will continue to analyze the resulting data to share insights with our collaborators in the scientific, medical, and advocacy communities.”

Phase 3 VITAL study

The VITAL study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in treatment-naïve patients with AL amyloidosis and cardiac dysfunction.

The study enrolled 260 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 or placebo via intravenous infusion every 28 days. Patients in both arms received concurrent standard of care therapy.

The composite primary endpoint was event-based, with all-cause mortality or cardiac hospitalizations counted as events.

The futility analysis, based on 103 adjudicated events of the 156 events specified to complete the study, was not statistically significant. The hazard ratio was 0.84 favoring NEOD001 versus the control arm.

Phase 2b PRONTO study

The PRONTO study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in previously treated patients with AL amyloidosis and persistent cardiac dysfunction.

The study enrolled 129 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 (n=66) or placebo (n=63) via intravenous infusion every 28 days.

There was no significant difference between the treatment arms for any of the study’s endpoints.

The primary endpoint was cardiac best response, as assessed by N-terminal pro B-type natriuretic peptide (NT-proBNP) through 12 months of treatment. This endpoint was achieved by 39.4% of patients in the NEOD001 arm and 47.6% in the placebo arm.

The NT-proBNP rate of change (slope) through 12 months of treatment was 9.80 in the NEOD001 arm and 81.42 in the placebo arm.

The mean change in Short-form 36 Physical Component Summary Score after 12 months of treatment was 0.19 and 0.97, respectively.

The median change in 6-Minute Walk Test distance after 12 months of treatment was 19.25 m and 8.00 m, respectively.

And the mean change in Neuropathy Impairment Score of the Lower Limb after 12 months of treatment was -1.20 and -0.60, respectively.

The rate of renal best response (as assessed by proteinuria and estimated glomerular filtration rate) through 12 months of treatment was 53.8% in the NEOD001 arm and 33.3% in the placebo arm.

The rate of all-cause mortality was 4.5% (n=3) and 9.5% (n=6), respectively.

Prothena said NEOD001 was generally safe and well tolerated in this trial.

Clinical question: Are there differences in mortality and health care resource utilization in patients treated by hospitalists, primary care physicians, or other generalists?

Background: Most hospitalized patients now are being cared for by hospitalists rather than their primary care physicians (PCP). Covering generalists, who lack a prior relationship with the patient, also care for hospitalized patients when their PCP is unavailable. Although past studies have found some differences in outcomes in patients when care was provided by hospitalists vs. PCPs, those studies have grouped covering generalists with PCPs, which could affect the data.

Clinical question: Are there differences in mortality and health care resource utilization in patients treated by hospitalists, primary care physicians, or other generalists?

Background: Most hospitalized patients now are being cared for by hospitalists rather than their primary care physicians (PCP). Covering generalists, who lack a prior relationship with the patient, also care for hospitalized patients when their PCP is unavailable. Although past studies have found some differences in outcomes in patients when care was provided by hospitalists vs. PCPs, those studies have grouped covering generalists with PCPs, which could affect the data.

Clinical question: Are there differences in mortality and health care resource utilization in patients treated by hospitalists, primary care physicians, or other generalists?

Background: Most hospitalized patients now are being cared for by hospitalists rather than their primary care physicians (PCP). Covering generalists, who lack a prior relationship with the patient, also care for hospitalized patients when their PCP is unavailable. Although past studies have found some differences in outcomes in patients when care was provided by hospitalists vs. PCPs, those studies have grouped covering generalists with PCPs, which could affect the data.

It’s time to introduce a new paradigm for comprehensive care of women’s physical and mental health in the 3 months after giving birth, according to the American College of Obstetricians and Gynecologists.

In their newly revised committee opinion on postpartum care, ACOG encouraged doctors to think of a woman’s immediate postpartum period as a “fourth trimester” during which better care for women may help reduce maternal deaths and morbidity. That care includes a 3-week postpartum visit and a more comprehensive one within 3 months post partum.

Components of comprehensive postpartum care

ACOG recommends the prenatal preparation for the postpartum period include discussions about infant feeding, “baby blues,” postpartum emotional health, parenting challenges, postpartum recovery from birth, long-term management of chronic health conditions, choosing a primary care provider for the mother’s ongoing care, her reproductive desires and choices, and any concerns about interpersonal or partner violence.

Before giving birth, a woman should develop a postpartum care plan with her physician and assemble a care team that includes her primary care providers along with family and friends who can provide support. The plan should include contact information for questions and written instructions about postpartum visits and follow-up care.

Prenatal planning also provides an opportunity to discuss a woman’s breastfeeding plans, goals, and questions as well as common physical problems that women may experience in the weeks after giving birth, such as heavy bleeding, pain, physical exhaustion, and urinary incontinence.

Physicians should inform women of the risks and benefits of becoming pregnant within 18 months and advise them not to have pregnancy intervals of less than 6 months. They should also ensure women know all their contraceptive options and should provide any information necessary for women to determine which methods best meet her needs.

The committee recommended a postpartum visit within the first 3 weeks after birth, instead of the current “6-week check,” that is timed and tailored to each woman’s particular needs. This visit allows assessment of postpartum depression risk and/or treatment and discussion of breastfeeding goals and/or difficulties. Approximately one in five women who stopped breastfeeding earlier than they wanted to had ceased within first 6 weeks post partum.

Woman-centered follow-up should be tailored to women’s individual needs and include a comprehensive postpartum visit no later than 12 weeks after giving birth. The comprehensive visit should include a complete assessment of the woman’s physical, social, and psychological well-being, including discussion of “mood and emotional well-being, infant care and feeding, sexuality, contraception, birth spacing, sleep and fatigue, physical recovery from birth, chronic disease management, and health maintenance,” the committee wrote.

The comprehensive visit should include the following components:

• Postpartum depression and anxiety screening.
• Screening for tobacco use and substance use.
• Follow-up on preexisting mental and physical health conditions.
• Assessment of mother’s confidence and comfort with newborn care, including feeding method, childcare strategy, identification of the child’s medical home, and recommended immunizations for all caregivers.
• Comfort and confidence with breastfeeding and management of any challenges, such as breastfeeding-associated pain; logistics and legal rights after returning to work or school; and fertility and contraception with breastfeeding.
• Assessment of material needs, including housing, utilities, food, and diapers.
• Guidance on sexuality, dyspareunia, reproductive life plans, contraception, and management of recurrent pregnancy complications, such as daily low-dose aspirin to reduce preeclampsia risk and 17a-hydroxyprogesterone caproate to reduce recurrent preterm birth.
• Sleep, fatigue, and coping options.
• Physical recovery from birth, including assessment of urinary and fecal continence and guidance on physical activity and a healthy weight.
• Chronic disease management and long-term implications of those conditions.
• Health maintenance, including review of vaccination history, needed vaccinations, and well-woman screenings, including Pap test and pelvic examination as indicated.

“However timed, the comprehensive postpartum visit is a medical appointment; it is not an ‘all-clear’ signal,” the authors wrote. “Obstetrician-gynecologists and other obstetric care providers should ensure that women, their families, and their employers understand that completion of the comprehensive postpartum visit does not obviate the need for continued recovery and support through 6 weeks’ post partum and beyond.”

Women with comorbidities or adverse birth outcomes

Women who had gestational diabetes, gestational hypertension, preeclampsia, eclampsia, or a preterm birth should be informed of their increased lifetime risk of cardiovascular and metabolic disease, the committee recommended. Women who have experienced a miscarriage, stillbirth, or neonatal death should also follow up with their provider, who can offer resources for emotional support and bereavement counseling, referrals as needed, a review of any laboratory or pathology results related to the loss and counseling regarding future risks and pregnancies.

The committee recommended that women with chronic medical conditions follow up with their ob.gyn. or other primary care providers to ensure ongoing coordinated care for hypertension, obesity, diabetes, thyroid disorders, renal disease, mood disorders, substance use disorders, seizure disorders, and any other chronic issues. Care should include assessment of medications, including antiepileptics and psychotropic drugs, that may require adjustment for postpartum physiology and, if relevant, breastfeeding.

Since half of postpartum strokes occur within the first 10 days after discharge, ACOG recommends women with other hypertensive disorders of pregnancy have a postpartum visit within 7-10 days after birth to assess blood pressure. A follow-up visit should occur within 72 hours for those with severe hypertension.

ACOG also recommended early postpartum follow-up for women with increased risk of complications, including postpartum depression, cesarean or perennial wound infections, lactation difficulties, or chronic conditions.

SOURCE: Obstet Gynecol 2018;131:e140-50.

It’s time to introduce a new paradigm for comprehensive care of women’s physical and mental health in the 3 months after giving birth, according to the American College of Obstetricians and Gynecologists.

In their newly revised committee opinion on postpartum care, ACOG encouraged doctors to think of a woman’s immediate postpartum period as a “fourth trimester” during which better care for women may help reduce maternal deaths and morbidity. That care includes a 3-week postpartum visit and a more comprehensive one within 3 months post partum.

Components of comprehensive postpartum care

ACOG recommends the prenatal preparation for the postpartum period include discussions about infant feeding, “baby blues,” postpartum emotional health, parenting challenges, postpartum recovery from birth, long-term management of chronic health conditions, choosing a primary care provider for the mother’s ongoing care, her reproductive desires and choices, and any concerns about interpersonal or partner violence.

Before giving birth, a woman should develop a postpartum care plan with her physician and assemble a care team that includes her primary care providers along with family and friends who can provide support. The plan should include contact information for questions and written instructions about postpartum visits and follow-up care.

Prenatal planning also provides an opportunity to discuss a woman’s breastfeeding plans, goals, and questions as well as common physical problems that women may experience in the weeks after giving birth, such as heavy bleeding, pain, physical exhaustion, and urinary incontinence.

Physicians should inform women of the risks and benefits of becoming pregnant within 18 months and advise them not to have pregnancy intervals of less than 6 months. They should also ensure women know all their contraceptive options and should provide any information necessary for women to determine which methods best meet her needs.

The committee recommended a postpartum visit within the first 3 weeks after birth, instead of the current “6-week check,” that is timed and tailored to each woman’s particular needs. This visit allows assessment of postpartum depression risk and/or treatment and discussion of breastfeeding goals and/or difficulties. Approximately one in five women who stopped breastfeeding earlier than they wanted to had ceased within first 6 weeks post partum.

Woman-centered follow-up should be tailored to women’s individual needs and include a comprehensive postpartum visit no later than 12 weeks after giving birth. The comprehensive visit should include a complete assessment of the woman’s physical, social, and psychological well-being, including discussion of “mood and emotional well-being, infant care and feeding, sexuality, contraception, birth spacing, sleep and fatigue, physical recovery from birth, chronic disease management, and health maintenance,” the committee wrote.

The comprehensive visit should include the following components:

• Postpartum depression and anxiety screening.
• Screening for tobacco use and substance use.
• Follow-up on preexisting mental and physical health conditions.
• Assessment of mother’s confidence and comfort with newborn care, including feeding method, childcare strategy, identification of the child’s medical home, and recommended immunizations for all caregivers.
• Comfort and confidence with breastfeeding and management of any challenges, such as breastfeeding-associated pain; logistics and legal rights after returning to work or school; and fertility and contraception with breastfeeding.
• Assessment of material needs, including housing, utilities, food, and diapers.
• Guidance on sexuality, dyspareunia, reproductive life plans, contraception, and management of recurrent pregnancy complications, such as daily low-dose aspirin to reduce preeclampsia risk and 17a-hydroxyprogesterone caproate to reduce recurrent preterm birth.
• Sleep, fatigue, and coping options.
• Physical recovery from birth, including assessment of urinary and fecal continence and guidance on physical activity and a healthy weight.
• Chronic disease management and long-term implications of those conditions.
• Health maintenance, including review of vaccination history, needed vaccinations, and well-woman screenings, including Pap test and pelvic examination as indicated.

“However timed, the comprehensive postpartum visit is a medical appointment; it is not an ‘all-clear’ signal,” the authors wrote. “Obstetrician-gynecologists and other obstetric care providers should ensure that women, their families, and their employers understand that completion of the comprehensive postpartum visit does not obviate the need for continued recovery and support through 6 weeks’ post partum and beyond.”

Women with comorbidities or adverse birth outcomes

Women who had gestational diabetes, gestational hypertension, preeclampsia, eclampsia, or a preterm birth should be informed of their increased lifetime risk of cardiovascular and metabolic disease, the committee recommended. Women who have experienced a miscarriage, stillbirth, or neonatal death should also follow up with their provider, who can offer resources for emotional support and bereavement counseling, referrals as needed, a review of any laboratory or pathology results related to the loss and counseling regarding future risks and pregnancies.

The committee recommended that women with chronic medical conditions follow up with their ob.gyn. or other primary care providers to ensure ongoing coordinated care for hypertension, obesity, diabetes, thyroid disorders, renal disease, mood disorders, substance use disorders, seizure disorders, and any other chronic issues. Care should include assessment of medications, including antiepileptics and psychotropic drugs, that may require adjustment for postpartum physiology and, if relevant, breastfeeding.

Since half of postpartum strokes occur within the first 10 days after discharge, ACOG recommends women with other hypertensive disorders of pregnancy have a postpartum visit within 7-10 days after birth to assess blood pressure. A follow-up visit should occur within 72 hours for those with severe hypertension.

ACOG also recommended early postpartum follow-up for women with increased risk of complications, including postpartum depression, cesarean or perennial wound infections, lactation difficulties, or chronic conditions.

SOURCE: Obstet Gynecol 2018;131:e140-50.

It’s time to introduce a new paradigm for comprehensive care of women’s physical and mental health in the 3 months after giving birth, according to the American College of Obstetricians and Gynecologists.

In their newly revised committee opinion on postpartum care, ACOG encouraged doctors to think of a woman’s immediate postpartum period as a “fourth trimester” during which better care for women may help reduce maternal deaths and morbidity. That care includes a 3-week postpartum visit and a more comprehensive one within 3 months post partum.

Components of comprehensive postpartum care

ACOG recommends the prenatal preparation for the postpartum period include discussions about infant feeding, “baby blues,” postpartum emotional health, parenting challenges, postpartum recovery from birth, long-term management of chronic health conditions, choosing a primary care provider for the mother’s ongoing care, her reproductive desires and choices, and any concerns about interpersonal or partner violence.

Before giving birth, a woman should develop a postpartum care plan with her physician and assemble a care team that includes her primary care providers along with family and friends who can provide support. The plan should include contact information for questions and written instructions about postpartum visits and follow-up care.

Prenatal planning also provides an opportunity to discuss a woman’s breastfeeding plans, goals, and questions as well as common physical problems that women may experience in the weeks after giving birth, such as heavy bleeding, pain, physical exhaustion, and urinary incontinence.

Physicians should inform women of the risks and benefits of becoming pregnant within 18 months and advise them not to have pregnancy intervals of less than 6 months. They should also ensure women know all their contraceptive options and should provide any information necessary for women to determine which methods best meet her needs.

The committee recommended a postpartum visit within the first 3 weeks after birth, instead of the current “6-week check,” that is timed and tailored to each woman’s particular needs. This visit allows assessment of postpartum depression risk and/or treatment and discussion of breastfeeding goals and/or difficulties. Approximately one in five women who stopped breastfeeding earlier than they wanted to had ceased within first 6 weeks post partum.

Woman-centered follow-up should be tailored to women’s individual needs and include a comprehensive postpartum visit no later than 12 weeks after giving birth. The comprehensive visit should include a complete assessment of the woman’s physical, social, and psychological well-being, including discussion of “mood and emotional well-being, infant care and feeding, sexuality, contraception, birth spacing, sleep and fatigue, physical recovery from birth, chronic disease management, and health maintenance,” the committee wrote.

The comprehensive visit should include the following components:

• Postpartum depression and anxiety screening.
• Screening for tobacco use and substance use.
• Follow-up on preexisting mental and physical health conditions.
• Assessment of mother’s confidence and comfort with newborn care, including feeding method, childcare strategy, identification of the child’s medical home, and recommended immunizations for all caregivers.
• Comfort and confidence with breastfeeding and management of any challenges, such as breastfeeding-associated pain; logistics and legal rights after returning to work or school; and fertility and contraception with breastfeeding.
• Assessment of material needs, including housing, utilities, food, and diapers.
• Guidance on sexuality, dyspareunia, reproductive life plans, contraception, and management of recurrent pregnancy complications, such as daily low-dose aspirin to reduce preeclampsia risk and 17a-hydroxyprogesterone caproate to reduce recurrent preterm birth.
• Sleep, fatigue, and coping options.
• Physical recovery from birth, including assessment of urinary and fecal continence and guidance on physical activity and a healthy weight.
• Chronic disease management and long-term implications of those conditions.
• Health maintenance, including review of vaccination history, needed vaccinations, and well-woman screenings, including Pap test and pelvic examination as indicated.

“However timed, the comprehensive postpartum visit is a medical appointment; it is not an ‘all-clear’ signal,” the authors wrote. “Obstetrician-gynecologists and other obstetric care providers should ensure that women, their families, and their employers understand that completion of the comprehensive postpartum visit does not obviate the need for continued recovery and support through 6 weeks’ post partum and beyond.”

Women with comorbidities or adverse birth outcomes

Women who had gestational diabetes, gestational hypertension, preeclampsia, eclampsia, or a preterm birth should be informed of their increased lifetime risk of cardiovascular and metabolic disease, the committee recommended. Women who have experienced a miscarriage, stillbirth, or neonatal death should also follow up with their provider, who can offer resources for emotional support and bereavement counseling, referrals as needed, a review of any laboratory or pathology results related to the loss and counseling regarding future risks and pregnancies.

The committee recommended that women with chronic medical conditions follow up with their ob.gyn. or other primary care providers to ensure ongoing coordinated care for hypertension, obesity, diabetes, thyroid disorders, renal disease, mood disorders, substance use disorders, seizure disorders, and any other chronic issues. Care should include assessment of medications, including antiepileptics and psychotropic drugs, that may require adjustment for postpartum physiology and, if relevant, breastfeeding.

Since half of postpartum strokes occur within the first 10 days after discharge, ACOG recommends women with other hypertensive disorders of pregnancy have a postpartum visit within 7-10 days after birth to assess blood pressure. A follow-up visit should occur within 72 hours for those with severe hypertension.

ACOG also recommended early postpartum follow-up for women with increased risk of complications, including postpartum depression, cesarean or perennial wound infections, lactation difficulties, or chronic conditions.

SOURCE: Obstet Gynecol 2018;131:e140-50.

Patients with systemic lupus erythematosus (SLE) who were hypocomplementemic and anti–double-stranded DNA (anti-dsDNA) positive took weekly subcutaneous belimumab in addition to their standard therapy and saw reduced disease activity and fatigue at 1 year, compared with patients taking a placebo, according to results of a phase 3, double-blinded study. These results suggest the subcutaneous version of the monoclonal antibody therapy could be administered at home without patients visiting a hospital, the investigators wrote in Arthritis and Rheumatology.

“Intravenous administration of belimumab is an obstacle to treatment for many patients due to the need to go to the hospital for drug infusions. Thus, a higher number of patients could benefit from this treatment,” Andrea Doria, MD, from the University of Padua (Italy) stated in a press release. “The self-administration of subcutaneous belimumab makes hospital access unnecessary, which leads to economic savings for patients and the community.”

enot-poloskun/iStock/Getty Images Plus

“Some aspects of this study were identified as potential limitations,” Dr. Doria and his colleagues wrote. “Within the hypocomplementemic and anti-dsDNA positive subset population, only 65.7% of patients received steroids greater than 7.5 mg/day at baseline; thus (as in the overall population), this endpoint was not powered for statistical significance. In addition, this study excluded patients with SELENA-SLEDAI less than 8, active nephritis, or active CNS disease at screening.”

The study was funded, conducted, and designed by GlaxoSmithKline. Five authors have shares in and are employees of GSK; another was an employee of GSK at the time of the study. Seven authors declared consulting fees, grants and other remuneration from pharmaceutical companies, including GSK.

SOURCE: Doria A et al. Arthritis Rheumatol. 2018 Apr 18. doi: 10.1002/art.40511.

Patients with systemic lupus erythematosus (SLE) who were hypocomplementemic and anti–double-stranded DNA (anti-dsDNA) positive took weekly subcutaneous belimumab in addition to their standard therapy and saw reduced disease activity and fatigue at 1 year, compared with patients taking a placebo, according to results of a phase 3, double-blinded study. These results suggest the subcutaneous version of the monoclonal antibody therapy could be administered at home without patients visiting a hospital, the investigators wrote in Arthritis and Rheumatology.

“Intravenous administration of belimumab is an obstacle to treatment for many patients due to the need to go to the hospital for drug infusions. Thus, a higher number of patients could benefit from this treatment,” Andrea Doria, MD, from the University of Padua (Italy) stated in a press release. “The self-administration of subcutaneous belimumab makes hospital access unnecessary, which leads to economic savings for patients and the community.”

enot-poloskun/iStock/Getty Images Plus

“Some aspects of this study were identified as potential limitations,” Dr. Doria and his colleagues wrote. “Within the hypocomplementemic and anti-dsDNA positive subset population, only 65.7% of patients received steroids greater than 7.5 mg/day at baseline; thus (as in the overall population), this endpoint was not powered for statistical significance. In addition, this study excluded patients with SELENA-SLEDAI less than 8, active nephritis, or active CNS disease at screening.”

The study was funded, conducted, and designed by GlaxoSmithKline. Five authors have shares in and are employees of GSK; another was an employee of GSK at the time of the study. Seven authors declared consulting fees, grants and other remuneration from pharmaceutical companies, including GSK.

SOURCE: Doria A et al. Arthritis Rheumatol. 2018 Apr 18. doi: 10.1002/art.40511.

Patients with systemic lupus erythematosus (SLE) who were hypocomplementemic and anti–double-stranded DNA (anti-dsDNA) positive took weekly subcutaneous belimumab in addition to their standard therapy and saw reduced disease activity and fatigue at 1 year, compared with patients taking a placebo, according to results of a phase 3, double-blinded study. These results suggest the subcutaneous version of the monoclonal antibody therapy could be administered at home without patients visiting a hospital, the investigators wrote in Arthritis and Rheumatology.

“Intravenous administration of belimumab is an obstacle to treatment for many patients due to the need to go to the hospital for drug infusions. Thus, a higher number of patients could benefit from this treatment,” Andrea Doria, MD, from the University of Padua (Italy) stated in a press release. “The self-administration of subcutaneous belimumab makes hospital access unnecessary, which leads to economic savings for patients and the community.”

enot-poloskun/iStock/Getty Images Plus

“Some aspects of this study were identified as potential limitations,” Dr. Doria and his colleagues wrote. “Within the hypocomplementemic and anti-dsDNA positive subset population, only 65.7% of patients received steroids greater than 7.5 mg/day at baseline; thus (as in the overall population), this endpoint was not powered for statistical significance. In addition, this study excluded patients with SELENA-SLEDAI less than 8, active nephritis, or active CNS disease at screening.”

The study was funded, conducted, and designed by GlaxoSmithKline. Five authors have shares in and are employees of GSK; another was an employee of GSK at the time of the study. Seven authors declared consulting fees, grants and other remuneration from pharmaceutical companies, including GSK.

SOURCE: Doria A et al. Arthritis Rheumatol. 2018 Apr 18. doi: 10.1002/art.40511.

Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.

Of 13 patients who did not have the most severe beta⁰/beta⁰ genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta⁰/beta⁰ genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.

At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.

“No clonal dominance related to vector integration was observed,” wrote Alexis Thompson, MD, and her collaborators, and replication-competent lentivirus had not been found in any patients.

Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the New England Journal of Medicine. Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.

Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.

There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.

[email protected]

SOURCE: Thompson A et al. N Engl J Med 2018;378:1479-93

Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.

Of 13 patients who did not have the most severe beta⁰/beta⁰ genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta⁰/beta⁰ genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.

At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.

“No clonal dominance related to vector integration was observed,” wrote Alexis Thompson, MD, and her collaborators, and replication-competent lentivirus had not been found in any patients.

Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the New England Journal of Medicine. Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.

Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.

There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.

[email protected]

SOURCE: Thompson A et al. N Engl J Med 2018;378:1479-93

Most beta thalassemia patients were off transfusions at a median of 26 months after receiving gene therapy via a lentiviral vector, according to new results of two phase 1/2 studies regarding the use of LentiGlobin in transfusion-dependent beta thalassemia.

Of 13 patients who did not have the most severe beta⁰/beta⁰ genotype, all but 1 has become transfusion independent post transplant. Among patients who either had the beta⁰/beta⁰ genotype or had two copies of the IVS1-110 mutation, transfusions were down a median 73% annually, and three of these patients with more severe thalassemia became transfusion independent.

At the time of last data collection, hemoglobin levels in individual patients ranged from 8.2-13.7 g/dL.

“No clonal dominance related to vector integration was observed,” wrote Alexis Thompson, MD, and her collaborators, and replication-competent lentivirus had not been found in any patients.

Hematopoietic cell transplant (HCT) is an option primarily for younger beta thalassemia patients who have an HLA-matched sibling donor, the researchers wrote in the New England Journal of Medicine. Gene therapy represents an alternative to the current standard of care for patients who are not candidates for allogeneic HCT, which – without a good match – carries increased risk for rejection and graft-versus-host disease.

Patients with beta thalassemia aged 35 years or younger and without advanced organ damage were enrolled in the two studies, one conducted internationally and one conducted at a single site in France.

There were some protocol differences between the two studies; notably, the French study used enhanced red cell transfusion for 3 or more months before stem cell mobilization “to enrich for bona fide hematopoietic stem cells in the harvested CD34+ cell compartment by suppressing the erythroid lineage expansion and the skewing that is seen in beta thalassemia,” wrote Dr. Thompson, professor of pediatrics at Northwestern University, Chicago, and her colleagues.

[email protected]

SOURCE: Thompson A et al. N Engl J Med 2018;378:1479-93

ORLANDO – Idarucizumab, the reversal agent for the anticoagulant dabigatran, appeared as effective in quickly reversing dabigatran’s effects in patients with severe renal dysfunction as in patients with normally working kidneys, in a post hoc analysis of data collected in the drug’s pivotal trial.

A standard dose of idarucizumab “works just as well in patients with bad kidney function as it does in patients with preserved kidney function,” John W. Eikelboom, MD, said at the annual meeting of the American College of Cardiology. “The time to cessation of bleeding and the degree of normal hemostasis achieved was consistent” across the entire range of renal function examined, from severe renal dysfunction, with a creatinine clearance rate of less than 30 mL/min, to normal function, with an estimated rate of 80 mL/min or greater.

Mitchel L. Zoler/MDedge News

The ability of idarucizumab (Praxbind), conditionally approved by the Food and Drug Administration in 2015 and then fully approved in April 2018, to work in patients with impaired renal function has been an open question and concern because dabigatran (Pradaxa) is excreted renally, so it builds to unusually high levels in patients with poor kidney function. “Plasma dabigatran levels might be sky high, so a standard dose of idarucizumab might not work. That’s been a fear of clinicians,” explained Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont.

To examine whether idarucizumab’s activity varied by renal function he used data from the patients enrolled in the RE-VERSE AD (Reversal Effects of Idarucizumab on Active Dabigatran) study, the pivotal dataset that led to idarucizumab’s U.S. approval. The new, post hoc analysis divided patients into four subgroups based on their kidney function, and focused on the 489 patients for whom renal data were available out of the 503 patients in the study (N Engl J Med. 2017 Aug 3;377[5]:431-41). The subgroups included 91 patients with severe dysfunction with a creatinine clearance rate of less than 30 mL/min; 127 with moderate dysfunction and a clearance rate of 30-49 mL/min; 163 with mild dysfunction and a clearance rate of 50-79 mL/min; and 108 with normal function and a creatinine clearance of at least 80 mL/min.

Patients in the subgroup with severe renal dysfunction had the worst clinical profile overall, and as predicted, had a markedly elevated average plasma level of dabigatran, 231 ng/mL, nearly five times higher than the 47-ng/mL average level in patients with normal renal function.

The ability of a single, standard dose of idarucizumab to reverse the anticoagulant effects of dabigatran were essentially identical across the four strata of renal activity, with 98% of patients in both the severely impaired subgroup and the normal subgroup having 100% reversal within 4 hours of treatment, Dr. Eikelboom reported. Every patient included in the analysis had more than 50% reversal.

The study followed patients to 12-24 hours after they received idarucizumab, and 55% of patients with severe renal dysfunction showed a plasma dabigatran level that crept back toward a clinically meaningful level and so might need a second idarucizumab dose. In contrast, this happened in 8% of patients with normal renal function.

In patients with severe renal dysfunction given idarucizumab, “be alert for a recurrent bleed,” which could require a second dose of idarucizumab, Dr. Eikelboom suggested.

[email protected]

SOURCE: Eikelboom JW et al. ACC 18, Abstract 1231M-11.

ORLANDO – Idarucizumab, the reversal agent for the anticoagulant dabigatran, appeared as effective in quickly reversing dabigatran’s effects in patients with severe renal dysfunction as in patients with normally working kidneys, in a post hoc analysis of data collected in the drug’s pivotal trial.

A standard dose of idarucizumab “works just as well in patients with bad kidney function as it does in patients with preserved kidney function,” John W. Eikelboom, MD, said at the annual meeting of the American College of Cardiology. “The time to cessation of bleeding and the degree of normal hemostasis achieved was consistent” across the entire range of renal function examined, from severe renal dysfunction, with a creatinine clearance rate of less than 30 mL/min, to normal function, with an estimated rate of 80 mL/min or greater.

Mitchel L. Zoler/MDedge News

The ability of idarucizumab (Praxbind), conditionally approved by the Food and Drug Administration in 2015 and then fully approved in April 2018, to work in patients with impaired renal function has been an open question and concern because dabigatran (Pradaxa) is excreted renally, so it builds to unusually high levels in patients with poor kidney function. “Plasma dabigatran levels might be sky high, so a standard dose of idarucizumab might not work. That’s been a fear of clinicians,” explained Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont.

To examine whether idarucizumab’s activity varied by renal function he used data from the patients enrolled in the RE-VERSE AD (Reversal Effects of Idarucizumab on Active Dabigatran) study, the pivotal dataset that led to idarucizumab’s U.S. approval. The new, post hoc analysis divided patients into four subgroups based on their kidney function, and focused on the 489 patients for whom renal data were available out of the 503 patients in the study (N Engl J Med. 2017 Aug 3;377[5]:431-41). The subgroups included 91 patients with severe dysfunction with a creatinine clearance rate of less than 30 mL/min; 127 with moderate dysfunction and a clearance rate of 30-49 mL/min; 163 with mild dysfunction and a clearance rate of 50-79 mL/min; and 108 with normal function and a creatinine clearance of at least 80 mL/min.

Patients in the subgroup with severe renal dysfunction had the worst clinical profile overall, and as predicted, had a markedly elevated average plasma level of dabigatran, 231 ng/mL, nearly five times higher than the 47-ng/mL average level in patients with normal renal function.

The ability of a single, standard dose of idarucizumab to reverse the anticoagulant effects of dabigatran were essentially identical across the four strata of renal activity, with 98% of patients in both the severely impaired subgroup and the normal subgroup having 100% reversal within 4 hours of treatment, Dr. Eikelboom reported. Every patient included in the analysis had more than 50% reversal.

The study followed patients to 12-24 hours after they received idarucizumab, and 55% of patients with severe renal dysfunction showed a plasma dabigatran level that crept back toward a clinically meaningful level and so might need a second idarucizumab dose. In contrast, this happened in 8% of patients with normal renal function.

In patients with severe renal dysfunction given idarucizumab, “be alert for a recurrent bleed,” which could require a second dose of idarucizumab, Dr. Eikelboom suggested.

[email protected]

SOURCE: Eikelboom JW et al. ACC 18, Abstract 1231M-11.

ORLANDO – Idarucizumab, the reversal agent for the anticoagulant dabigatran, appeared as effective in quickly reversing dabigatran’s effects in patients with severe renal dysfunction as in patients with normally working kidneys, in a post hoc analysis of data collected in the drug’s pivotal trial.

A standard dose of idarucizumab “works just as well in patients with bad kidney function as it does in patients with preserved kidney function,” John W. Eikelboom, MD, said at the annual meeting of the American College of Cardiology. “The time to cessation of bleeding and the degree of normal hemostasis achieved was consistent” across the entire range of renal function examined, from severe renal dysfunction, with a creatinine clearance rate of less than 30 mL/min, to normal function, with an estimated rate of 80 mL/min or greater.

Mitchel L. Zoler/MDedge News

The ability of idarucizumab (Praxbind), conditionally approved by the Food and Drug Administration in 2015 and then fully approved in April 2018, to work in patients with impaired renal function has been an open question and concern because dabigatran (Pradaxa) is excreted renally, so it builds to unusually high levels in patients with poor kidney function. “Plasma dabigatran levels might be sky high, so a standard dose of idarucizumab might not work. That’s been a fear of clinicians,” explained Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont.

To examine whether idarucizumab’s activity varied by renal function he used data from the patients enrolled in the RE-VERSE AD (Reversal Effects of Idarucizumab on Active Dabigatran) study, the pivotal dataset that led to idarucizumab’s U.S. approval. The new, post hoc analysis divided patients into four subgroups based on their kidney function, and focused on the 489 patients for whom renal data were available out of the 503 patients in the study (N Engl J Med. 2017 Aug 3;377[5]:431-41). The subgroups included 91 patients with severe dysfunction with a creatinine clearance rate of less than 30 mL/min; 127 with moderate dysfunction and a clearance rate of 30-49 mL/min; 163 with mild dysfunction and a clearance rate of 50-79 mL/min; and 108 with normal function and a creatinine clearance of at least 80 mL/min.

Patients in the subgroup with severe renal dysfunction had the worst clinical profile overall, and as predicted, had a markedly elevated average plasma level of dabigatran, 231 ng/mL, nearly five times higher than the 47-ng/mL average level in patients with normal renal function.

The ability of a single, standard dose of idarucizumab to reverse the anticoagulant effects of dabigatran were essentially identical across the four strata of renal activity, with 98% of patients in both the severely impaired subgroup and the normal subgroup having 100% reversal within 4 hours of treatment, Dr. Eikelboom reported. Every patient included in the analysis had more than 50% reversal.

The study followed patients to 12-24 hours after they received idarucizumab, and 55% of patients with severe renal dysfunction showed a plasma dabigatran level that crept back toward a clinically meaningful level and so might need a second idarucizumab dose. In contrast, this happened in 8% of patients with normal renal function.

In patients with severe renal dysfunction given idarucizumab, “be alert for a recurrent bleed,” which could require a second dose of idarucizumab, Dr. Eikelboom suggested.

[email protected]

SOURCE: Eikelboom JW et al. ACC 18, Abstract 1231M-11.

Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008) to Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma

NCT02306161

Sponsor: National Cancer Institute (NCI)

Principal Investigator: Steven DuBois, Children’s Oncology Group and Dana-Farber Cancer Institute, Boston.

Study locations: Over 300 U.S. cancer centers

Study summary: This randomized phase 3 trial examines whether the monoclonal antibody ganitumab plus combination chemotherapy (vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide) improves event-free survival for patients with newly-diagnosed, metastatic Ewing sarcoma. Secondary outcomes include overall survival rate and comparative evaluations of toxicity.

Patients are randomized to induction and consolidation therapy with vincristine sulfate, doxorubicin hydrochloride and cyclophosphamide [VDC] and ifosfamide and etoposide [IE]) or to the same regimen plus ganitumab. Between weeks 13-18 of the trial, patients undergo surgery and/or radiation therapy for local control. Patients with lung metastases undergo definitive stereotactic body radiation therapy or external beam radiation therapy over 5 days.

Study inclusion summary: Patients up to 50 years old are eligible to participate in this trial if they have newly-diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site. Submission of pre-treatment serum, tumor tissue and whole blood is required. Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery. Creatinine clearance or radioisotope glomerular filtration rate (GFR) must be at least 70 mL/min/1.73 m2 or greater. Total bilirubin must be less than 1.5 times the upper limit of normal, alanine aminotransferase must be less than 3 times the upper limit of normal, blood sugar must be normal, and heart ejection fraction must exceed 50%.

Induction therapy: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2; and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 5, and 9; and ifosfamide IV over 1 hour on days 1 to 5 and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 7, and 11. Patients in the control group receive induction therapy and placebo and patients in the treatment group receive induction therapy and ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11.

Consolidation therapy: Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1, 7, 9, and 13; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 1 and 7; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 7, 9, and 13; ifosfamide IV over 1 hour on days 1 to 5 of weeks 3, 5, 11, and 15; and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 5, 11, and 15. In addition to this standard consolidation therapy, pPatients in the active treatment group receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15.

Maintenance therapy: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, and 22.

Follow up: After completion of study treatment, patients are followed for 10 years.

Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma

NCT02567435

Sponsor: National Cancer Institute (NCI)

Principal Investigator: Abha Gupta, Children’s Oncology Group, The Hospital for Sick Children and Princess Margaret Cancer Centre.

Study locations: 293 cancer centers in the U.S. and Canada

Study summary: This randomized phase 3 trial compares standard combination chemotherapy with and without temsirolimus for patients with rhabdomyosarcoma that has an intermediate chance of recurrence after treatment. It is not yet known whether combination chemotherapy or combination chemotherapy plus temsirolimus is more effective in treating patients with intermediate-risk rhabdomyosarcoma.

Study inclusion summary: Patients up to age 40 with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study. Lansky performance status score must be at least 50 for patients age 16 years and under; Karnofsky performance status score must be 50 or greater for patients over age 16. Peripheral absolute neutrophil count must be at least 750/uL and platelet count at least 75,000/uL. Creatinine clearance or radioisotope glomerular filtration rate must be at least 70 mL/min/1.73 m2. Total bilirubin must be no more than 1.5 times the upper limit of normal for patient age.

Treatment regimen: Patients are randomized to one of three study arms. One group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. The second group receives the same regimen plus temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. The third group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients in all three groups also undergo radiation therapy beginning at week 13 for 6 weeks. Treatment continues in all three groups in the absence of disease progression or unacceptable toxicity.

Outcome Measures: The primary outcome measure is event-free survival (EFS) measured from study enrollment to the first occurrence of progression, relapse, second malignant neoplasm, or death as a first event. The secondary outcome measure is overall survival measured from study enrollment to death from any cause, assessed up to 10 years. TSJ

Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008) to Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma

NCT02306161

Sponsor: National Cancer Institute (NCI)

Principal Investigator: Steven DuBois, Children’s Oncology Group and Dana-Farber Cancer Institute, Boston.

Study locations: Over 300 U.S. cancer centers

Study summary: This randomized phase 3 trial examines whether the monoclonal antibody ganitumab plus combination chemotherapy (vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide) improves event-free survival for patients with newly-diagnosed, metastatic Ewing sarcoma. Secondary outcomes include overall survival rate and comparative evaluations of toxicity.

Patients are randomized to induction and consolidation therapy with vincristine sulfate, doxorubicin hydrochloride and cyclophosphamide [VDC] and ifosfamide and etoposide [IE]) or to the same regimen plus ganitumab. Between weeks 13-18 of the trial, patients undergo surgery and/or radiation therapy for local control. Patients with lung metastases undergo definitive stereotactic body radiation therapy or external beam radiation therapy over 5 days.

Study inclusion summary: Patients up to 50 years old are eligible to participate in this trial if they have newly-diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site. Submission of pre-treatment serum, tumor tissue and whole blood is required. Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery. Creatinine clearance or radioisotope glomerular filtration rate (GFR) must be at least 70 mL/min/1.73 m2 or greater. Total bilirubin must be less than 1.5 times the upper limit of normal, alanine aminotransferase must be less than 3 times the upper limit of normal, blood sugar must be normal, and heart ejection fraction must exceed 50%.

Induction therapy: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2; and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 5, and 9; and ifosfamide IV over 1 hour on days 1 to 5 and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 7, and 11. Patients in the control group receive induction therapy and placebo and patients in the treatment group receive induction therapy and ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11.

Consolidation therapy: Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1, 7, 9, and 13; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 1 and 7; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 7, 9, and 13; ifosfamide IV over 1 hour on days 1 to 5 of weeks 3, 5, 11, and 15; and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 5, 11, and 15. In addition to this standard consolidation therapy, pPatients in the active treatment group receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15.

Maintenance therapy: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, and 22.

Follow up: After completion of study treatment, patients are followed for 10 years.

Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma

NCT02567435

Sponsor: National Cancer Institute (NCI)

Principal Investigator: Abha Gupta, Children’s Oncology Group, The Hospital for Sick Children and Princess Margaret Cancer Centre.

Study locations: 293 cancer centers in the U.S. and Canada

Study summary: This randomized phase 3 trial compares standard combination chemotherapy with and without temsirolimus for patients with rhabdomyosarcoma that has an intermediate chance of recurrence after treatment. It is not yet known whether combination chemotherapy or combination chemotherapy plus temsirolimus is more effective in treating patients with intermediate-risk rhabdomyosarcoma.

Study inclusion summary: Patients up to age 40 with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study. Lansky performance status score must be at least 50 for patients age 16 years and under; Karnofsky performance status score must be 50 or greater for patients over age 16. Peripheral absolute neutrophil count must be at least 750/uL and platelet count at least 75,000/uL. Creatinine clearance or radioisotope glomerular filtration rate must be at least 70 mL/min/1.73 m2. Total bilirubin must be no more than 1.5 times the upper limit of normal for patient age.

Treatment regimen: Patients are randomized to one of three study arms. One group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. The second group receives the same regimen plus temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. The third group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients in all three groups also undergo radiation therapy beginning at week 13 for 6 weeks. Treatment continues in all three groups in the absence of disease progression or unacceptable toxicity.

Outcome Measures: The primary outcome measure is event-free survival (EFS) measured from study enrollment to the first occurrence of progression, relapse, second malignant neoplasm, or death as a first event. The secondary outcome measure is overall survival measured from study enrollment to death from any cause, assessed up to 10 years. TSJ

Randomized Phase 3 Trial Evaluating the Addition of the IGF-1R Monoclonal Antibody Ganitumab (AMG 479, NSC# 750008) to Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma

NCT02306161

Sponsor: National Cancer Institute (NCI)

Principal Investigator: Steven DuBois, Children’s Oncology Group and Dana-Farber Cancer Institute, Boston.

Study locations: Over 300 U.S. cancer centers

Study summary: This randomized phase 3 trial examines whether the monoclonal antibody ganitumab plus combination chemotherapy (vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide) improves event-free survival for patients with newly-diagnosed, metastatic Ewing sarcoma. Secondary outcomes include overall survival rate and comparative evaluations of toxicity.

Patients are randomized to induction and consolidation therapy with vincristine sulfate, doxorubicin hydrochloride and cyclophosphamide [VDC] and ifosfamide and etoposide [IE]) or to the same regimen plus ganitumab. Between weeks 13-18 of the trial, patients undergo surgery and/or radiation therapy for local control. Patients with lung metastases undergo definitive stereotactic body radiation therapy or external beam radiation therapy over 5 days.

Study inclusion summary: Patients up to 50 years old are eligible to participate in this trial if they have newly-diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site. Submission of pre-treatment serum, tumor tissue and whole blood is required. Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery. Creatinine clearance or radioisotope glomerular filtration rate (GFR) must be at least 70 mL/min/1.73 m2 or greater. Total bilirubin must be less than 1.5 times the upper limit of normal, alanine aminotransferase must be less than 3 times the upper limit of normal, blood sugar must be normal, and heart ejection fraction must exceed 50%.

Induction therapy: Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2; and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 5, and 9; and ifosfamide IV over 1 hour on days 1 to 5 and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 7, and 11. Patients in the control group receive induction therapy and placebo and patients in the treatment group receive induction therapy and ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11.

Consolidation therapy: Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1, 7, 9, and 13; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 1 and 7; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 7, 9, and 13; ifosfamide IV over 1 hour on days 1 to 5 of weeks 3, 5, 11, and 15; and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 5, 11, and 15. In addition to this standard consolidation therapy, pPatients in the active treatment group receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15.

Maintenance therapy: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, and 22.

Follow up: After completion of study treatment, patients are followed for 10 years.

Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma

NCT02567435

Sponsor: National Cancer Institute (NCI)

Principal Investigator: Abha Gupta, Children’s Oncology Group, The Hospital for Sick Children and Princess Margaret Cancer Centre.

Study locations: 293 cancer centers in the U.S. and Canada

Study summary: This randomized phase 3 trial compares standard combination chemotherapy with and without temsirolimus for patients with rhabdomyosarcoma that has an intermediate chance of recurrence after treatment. It is not yet known whether combination chemotherapy or combination chemotherapy plus temsirolimus is more effective in treating patients with intermediate-risk rhabdomyosarcoma.

Study inclusion summary: Patients up to age 40 with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification, are eligible to enroll on the study. Lansky performance status score must be at least 50 for patients age 16 years and under; Karnofsky performance status score must be 50 or greater for patients over age 16. Peripheral absolute neutrophil count must be at least 750/uL and platelet count at least 75,000/uL. Creatinine clearance or radioisotope glomerular filtration rate must be at least 70 mL/min/1.73 m2. Total bilirubin must be no more than 1.5 times the upper limit of normal for patient age.

Treatment regimen: Patients are randomized to one of three study arms. One group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. The second group receives the same regimen plus temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. The third group receives vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients in all three groups also undergo radiation therapy beginning at week 13 for 6 weeks. Treatment continues in all three groups in the absence of disease progression or unacceptable toxicity.

Outcome Measures: The primary outcome measure is event-free survival (EFS) measured from study enrollment to the first occurrence of progression, relapse, second malignant neoplasm, or death as a first event. The secondary outcome measure is overall survival measured from study enrollment to death from any cause, assessed up to 10 years. TSJ

DALLAS – A picosecond 755-nm laser with focus lens array can serve as a safe, nonsurgical option for neck rejuvenation in patients with Fitzpatrick skin types I-III, especially for those who seek treatments with minimal downtime.

“It’s important to note that response was variable, but many patients were satisfied with the treatment,” Hana Jeon, MD said at the annual conference of the American Society for Laser Medicine and Surgery, Inc. “Further studies are needed to identify the clinical characteristics of neck laxity that would most benefit from this treatment.”

Hana Jeon, MD

Dr. Jeon reported that the average pain score during the procedure was 4.7 on a 10-point scale. Forced-air cooling was used for comfort, and on average, mild redness following the treatment lasted less than 1 day (a mean of 0.6 days, with a range of 0-5 days). Mild pain also lasted less than 1 day (a mean of 0.1 days, with a range of 0-2 days). No swelling, crusting, bruising, bleeding, infection, blistering, scarring, burn, or dyspigmentation occurred.

Hana Jeon, MD

At 3 months, 35% of patients said they would be “somewhat likely” to recommend the procedure, and 30% said they would be “extremely likely” to recommend it.

Dr. Jeon reported having no financial disclosures.

[email protected]

DALLAS – A picosecond 755-nm laser with focus lens array can serve as a safe, nonsurgical option for neck rejuvenation in patients with Fitzpatrick skin types I-III, especially for those who seek treatments with minimal downtime.

“It’s important to note that response was variable, but many patients were satisfied with the treatment,” Hana Jeon, MD said at the annual conference of the American Society for Laser Medicine and Surgery, Inc. “Further studies are needed to identify the clinical characteristics of neck laxity that would most benefit from this treatment.”

Hana Jeon, MD

Dr. Jeon reported that the average pain score during the procedure was 4.7 on a 10-point scale. Forced-air cooling was used for comfort, and on average, mild redness following the treatment lasted less than 1 day (a mean of 0.6 days, with a range of 0-5 days). Mild pain also lasted less than 1 day (a mean of 0.1 days, with a range of 0-2 days). No swelling, crusting, bruising, bleeding, infection, blistering, scarring, burn, or dyspigmentation occurred.

Hana Jeon, MD

At 3 months, 35% of patients said they would be “somewhat likely” to recommend the procedure, and 30% said they would be “extremely likely” to recommend it.

Dr. Jeon reported having no financial disclosures.

[email protected]

DALLAS – A picosecond 755-nm laser with focus lens array can serve as a safe, nonsurgical option for neck rejuvenation in patients with Fitzpatrick skin types I-III, especially for those who seek treatments with minimal downtime.

“It’s important to note that response was variable, but many patients were satisfied with the treatment,” Hana Jeon, MD said at the annual conference of the American Society for Laser Medicine and Surgery, Inc. “Further studies are needed to identify the clinical characteristics of neck laxity that would most benefit from this treatment.”

Hana Jeon, MD

Dr. Jeon reported that the average pain score during the procedure was 4.7 on a 10-point scale. Forced-air cooling was used for comfort, and on average, mild redness following the treatment lasted less than 1 day (a mean of 0.6 days, with a range of 0-5 days). Mild pain also lasted less than 1 day (a mean of 0.1 days, with a range of 0-2 days). No swelling, crusting, bruising, bleeding, infection, blistering, scarring, burn, or dyspigmentation occurred.

Hana Jeon, MD

At 3 months, 35% of patients said they would be “somewhat likely” to recommend the procedure, and 30% said they would be “extremely likely” to recommend it.

Dr. Jeon reported having no financial disclosures.

[email protected]

WASHINGTON – Present infections make patients more likely to develop primary Sjögren’s syndrome, according to a study presented at an International Symposium on Sjögren’s Syndrome.

“We observed a consistent association between infections and the subsequent development of primary Sjögren’s syndrome,” said Johannes Mofors of the department of medicine at the Karolinska University Hospital, Stockholm, in his presentation. “Infections of certain anatomical sites have different associations to Sjögren’s.”

With risk measurements primarily reliant on detecting the presence of MHC genes, this knowledge could be helpful in identifying at-risk patients and give physicians the chance to act before the syndrome emerges, according to Mr. Mofors.

Investigators conducted a retrospective, multicenter, controlled cohort study of 9,993 Swedish individuals from the country’s national patient registry to observe the association between infections and Sjögren’s.

Patients were an average age of 55 years, with either an SSA or SSB infection, with an average observational period of 16 years before diagnosis.

Of the patients with Sjögren’s disease, 21% reported one or more infections prior to diagnosis, compared with 12% among the control group.

When assessing patients by their type of infection, Mr. Mofors and his colleagues found the likelihood of developing Sjögren’s varied depending on which infection was present.

[email protected]

WASHINGTON – Present infections make patients more likely to develop primary Sjögren’s syndrome, according to a study presented at an International Symposium on Sjögren’s Syndrome.

“We observed a consistent association between infections and the subsequent development of primary Sjögren’s syndrome,” said Johannes Mofors of the department of medicine at the Karolinska University Hospital, Stockholm, in his presentation. “Infections of certain anatomical sites have different associations to Sjögren’s.”

With risk measurements primarily reliant on detecting the presence of MHC genes, this knowledge could be helpful in identifying at-risk patients and give physicians the chance to act before the syndrome emerges, according to Mr. Mofors.

Investigators conducted a retrospective, multicenter, controlled cohort study of 9,993 Swedish individuals from the country’s national patient registry to observe the association between infections and Sjögren’s.

Patients were an average age of 55 years, with either an SSA or SSB infection, with an average observational period of 16 years before diagnosis.

Of the patients with Sjögren’s disease, 21% reported one or more infections prior to diagnosis, compared with 12% among the control group.

When assessing patients by their type of infection, Mr. Mofors and his colleagues found the likelihood of developing Sjögren’s varied depending on which infection was present.

[email protected]

WASHINGTON – Present infections make patients more likely to develop primary Sjögren’s syndrome, according to a study presented at an International Symposium on Sjögren’s Syndrome.

“We observed a consistent association between infections and the subsequent development of primary Sjögren’s syndrome,” said Johannes Mofors of the department of medicine at the Karolinska University Hospital, Stockholm, in his presentation. “Infections of certain anatomical sites have different associations to Sjögren’s.”

With risk measurements primarily reliant on detecting the presence of MHC genes, this knowledge could be helpful in identifying at-risk patients and give physicians the chance to act before the syndrome emerges, according to Mr. Mofors.

Investigators conducted a retrospective, multicenter, controlled cohort study of 9,993 Swedish individuals from the country’s national patient registry to observe the association between infections and Sjögren’s.

Patients were an average age of 55 years, with either an SSA or SSB infection, with an average observational period of 16 years before diagnosis.

Of the patients with Sjögren’s disease, 21% reported one or more infections prior to diagnosis, compared with 12% among the control group.

When assessing patients by their type of infection, Mr. Mofors and his colleagues found the likelihood of developing Sjögren’s varied depending on which infection was present.

[email protected]

BOSTON – Having a great idea is just the first step to landing a financial partner in device development – backers also scrutinize more intangible qualities.

The willingness to work as part of a team, the ability to project realistic expectations, the fortitude to take risks and persevere when circumstances get tough – these attributes are critical to forging a strong strategic alliance with a financial partner, Brian Tinkham said at the 2018 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

Robert Lodge/MDedge News

Put your own skin in the game

“To me, ‘skin in the game’ is mainly money. Investing your own money, your family’s money, changes the way you behave at the board meeting and when you spend that money,” Mr. Tinkham said. “We like people who are all in on this. When I see an entrepreneur who’s showing a return that’s not good enough for his own investment, I can lose confidence and trust. We want people who won’t walk away from their money, their family’s money, or my money; when times get tough and challenging, decisions need to be made.”

Be realistic

There’s a difference between confidence and irrational confidence, Mr. Tinkham said. “If you come to me presenting a game plan that says you’ll have a commercially viable product in 1 year for a $500,000 investment, you’ll shoot your credibility right off. We know exactly how hard it is to build a $10 million business, never mind a $100 million business. When you obviously don’t understand what lies ahead of you, it hurts your credibility. Work with people who have experience and let them help you present your ideas and goals in a realistic way, and that will help with raising capital so you can execute your plan.”

Be capital efficient

“The key takeaway here is that raising $100 million doesn’t necessarily make for a strong return for investors. The strong return comes with $20-$40 million raised. Most likely businesses that have raised that much have built a commercial structure, provided proof of concept with some actual sales, and generated enough customer interest to attract strategic partners.”

Location, location, location

“This is so important when you’re developing technology: You need to know where the people with high levels of competency are, and where the money is. If you don’t live near these localities, get on a plane and get there – that’s where the business is being done.”

California and the Philadelphia-Boston-New York corridor are the two biggest med-tech and investor hot spots in the United States, Mr. Tinkham noted. Smaller centers of innovation are scattered around the country, including Seattle, Denver, Minneapolis, Chicago, Pittsburgh, Washington, Raleigh-Durham, Atlanta, Austin, and Phoenix.
 

Be patient

“Adopting a new technology takes time, and the more disruptive the idea, the longer it takes to achieve market adoption. Translating that into med-tech, the time from founding a company to exit will take more than 5 years. Only 10% of companies do it in less time than that,” Mr. Tinkham said. “And you have to remember that not all of the exits we see are good ones – they can be exits in which investors lose most of the capital they’ve brought into the company.”

De-risk

Be the entrepreneur who takes a vision to a viable product.

“Most physician entrepreneurs come up with an idea and protect it – but don’t move it further. We want to see an idea that’s been created and then de-risked. You protect it, you prototype it, go into preclinical studies, then clinically validate it or obtain regulatory approval. And then in the end, to us the best measure is your revenue. Are customers buying it? Do they see in it the same value that you, the entrepreneur, sees? If you can get it there, you’ve got something. The further you de-risk something, the more attractive you become.”

Are you a physician innovator?

If you have an idea for a new technology to improve gastroenterology, the AGA Center for GI Innovation and Technology can help you through the device development and adoption process.

Get in touch with us at [email protected].

[email protected]

BOSTON – Having a great idea is just the first step to landing a financial partner in device development – backers also scrutinize more intangible qualities.

The willingness to work as part of a team, the ability to project realistic expectations, the fortitude to take risks and persevere when circumstances get tough – these attributes are critical to forging a strong strategic alliance with a financial partner, Brian Tinkham said at the 2018 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

Robert Lodge/MDedge News

Put your own skin in the game

“To me, ‘skin in the game’ is mainly money. Investing your own money, your family’s money, changes the way you behave at the board meeting and when you spend that money,” Mr. Tinkham said. “We like people who are all in on this. When I see an entrepreneur who’s showing a return that’s not good enough for his own investment, I can lose confidence and trust. We want people who won’t walk away from their money, their family’s money, or my money; when times get tough and challenging, decisions need to be made.”

Be realistic

There’s a difference between confidence and irrational confidence, Mr. Tinkham said. “If you come to me presenting a game plan that says you’ll have a commercially viable product in 1 year for a $500,000 investment, you’ll shoot your credibility right off. We know exactly how hard it is to build a $10 million business, never mind a $100 million business. When you obviously don’t understand what lies ahead of you, it hurts your credibility. Work with people who have experience and let them help you present your ideas and goals in a realistic way, and that will help with raising capital so you can execute your plan.”

Be capital efficient

“The key takeaway here is that raising $100 million doesn’t necessarily make for a strong return for investors. The strong return comes with $20-$40 million raised. Most likely businesses that have raised that much have built a commercial structure, provided proof of concept with some actual sales, and generated enough customer interest to attract strategic partners.”

Location, location, location

“This is so important when you’re developing technology: You need to know where the people with high levels of competency are, and where the money is. If you don’t live near these localities, get on a plane and get there – that’s where the business is being done.”

California and the Philadelphia-Boston-New York corridor are the two biggest med-tech and investor hot spots in the United States, Mr. Tinkham noted. Smaller centers of innovation are scattered around the country, including Seattle, Denver, Minneapolis, Chicago, Pittsburgh, Washington, Raleigh-Durham, Atlanta, Austin, and Phoenix.
 

Be patient

“Adopting a new technology takes time, and the more disruptive the idea, the longer it takes to achieve market adoption. Translating that into med-tech, the time from founding a company to exit will take more than 5 years. Only 10% of companies do it in less time than that,” Mr. Tinkham said. “And you have to remember that not all of the exits we see are good ones – they can be exits in which investors lose most of the capital they’ve brought into the company.”

De-risk

Be the entrepreneur who takes a vision to a viable product.

“Most physician entrepreneurs come up with an idea and protect it – but don’t move it further. We want to see an idea that’s been created and then de-risked. You protect it, you prototype it, go into preclinical studies, then clinically validate it or obtain regulatory approval. And then in the end, to us the best measure is your revenue. Are customers buying it? Do they see in it the same value that you, the entrepreneur, sees? If you can get it there, you’ve got something. The further you de-risk something, the more attractive you become.”

Are you a physician innovator?

If you have an idea for a new technology to improve gastroenterology, the AGA Center for GI Innovation and Technology can help you through the device development and adoption process.

Get in touch with us at [email protected].

[email protected]

BOSTON – Having a great idea is just the first step to landing a financial partner in device development – backers also scrutinize more intangible qualities.

The willingness to work as part of a team, the ability to project realistic expectations, the fortitude to take risks and persevere when circumstances get tough – these attributes are critical to forging a strong strategic alliance with a financial partner, Brian Tinkham said at the 2018 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology.

Robert Lodge/MDedge News

Put your own skin in the game

“To me, ‘skin in the game’ is mainly money. Investing your own money, your family’s money, changes the way you behave at the board meeting and when you spend that money,” Mr. Tinkham said. “We like people who are all in on this. When I see an entrepreneur who’s showing a return that’s not good enough for his own investment, I can lose confidence and trust. We want people who won’t walk away from their money, their family’s money, or my money; when times get tough and challenging, decisions need to be made.”

Be realistic

There’s a difference between confidence and irrational confidence, Mr. Tinkham said. “If you come to me presenting a game plan that says you’ll have a commercially viable product in 1 year for a $500,000 investment, you’ll shoot your credibility right off. We know exactly how hard it is to build a $10 million business, never mind a $100 million business. When you obviously don’t understand what lies ahead of you, it hurts your credibility. Work with people who have experience and let them help you present your ideas and goals in a realistic way, and that will help with raising capital so you can execute your plan.”

Be capital efficient

“The key takeaway here is that raising $100 million doesn’t necessarily make for a strong return for investors. The strong return comes with $20-$40 million raised. Most likely businesses that have raised that much have built a commercial structure, provided proof of concept with some actual sales, and generated enough customer interest to attract strategic partners.”

Location, location, location

“This is so important when you’re developing technology: You need to know where the people with high levels of competency are, and where the money is. If you don’t live near these localities, get on a plane and get there – that’s where the business is being done.”

California and the Philadelphia-Boston-New York corridor are the two biggest med-tech and investor hot spots in the United States, Mr. Tinkham noted. Smaller centers of innovation are scattered around the country, including Seattle, Denver, Minneapolis, Chicago, Pittsburgh, Washington, Raleigh-Durham, Atlanta, Austin, and Phoenix.
 

Be patient

“Adopting a new technology takes time, and the more disruptive the idea, the longer it takes to achieve market adoption. Translating that into med-tech, the time from founding a company to exit will take more than 5 years. Only 10% of companies do it in less time than that,” Mr. Tinkham said. “And you have to remember that not all of the exits we see are good ones – they can be exits in which investors lose most of the capital they’ve brought into the company.”

De-risk

Be the entrepreneur who takes a vision to a viable product.

“Most physician entrepreneurs come up with an idea and protect it – but don’t move it further. We want to see an idea that’s been created and then de-risked. You protect it, you prototype it, go into preclinical studies, then clinically validate it or obtain regulatory approval. And then in the end, to us the best measure is your revenue. Are customers buying it? Do they see in it the same value that you, the entrepreneur, sees? If you can get it there, you’ve got something. The further you de-risk something, the more attractive you become.”

Are you a physician innovator?

If you have an idea for a new technology to improve gastroenterology, the AGA Center for GI Innovation and Technology can help you through the device development and adoption process.

Get in touch with us at [email protected].

[email protected]