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FDA: More metformin extended-release tablets recalled
Two lots of metformin HCl extended-release tablets have been recalled by Viona Pharmaceuticals because unacceptable levels of nitrosodimethylamine (NDMA), a likely carcinogen, were found in the 750-mg tablets.
According to a June 11 alert from the Food and Drug Administration, the affected lot numbers are M915601 and M915602.
This generic product was made by Cadila Healthcare, Ahmedabad, India, in November 2019 with an expiration date of October 2021, and distributed throughout the United States. The pill is white to off-white, capsule-shaped, uncoated tablets, debossed with “Z”, “C” on one side and “20” on the other side.
No adverse events related to the lots involved in the recall have been reported, the FDA said. It also recommends that clinicians continue to prescribe metformin when clinically appropriate.
In late 2019, the FDA announced it had become aware of NDMA in some metformin products in other countries. The agency immediately began testing to determine whether the metformin in the U.S. supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types, which included recalls of hypertension and heartburn medications within the past 3 years.
In February 2020, the FDA reported that they hadn’t found NDMA levels that exceeded the acceptable daily intake. But starting in May 2020, voluntary recalls by, numerous manufacturers have been announced as levels of the compound exceeded that cutoff.
Two lots of metformin HCl extended-release tablets have been recalled by Viona Pharmaceuticals because unacceptable levels of nitrosodimethylamine (NDMA), a likely carcinogen, were found in the 750-mg tablets.
According to a June 11 alert from the Food and Drug Administration, the affected lot numbers are M915601 and M915602.
This generic product was made by Cadila Healthcare, Ahmedabad, India, in November 2019 with an expiration date of October 2021, and distributed throughout the United States. The pill is white to off-white, capsule-shaped, uncoated tablets, debossed with “Z”, “C” on one side and “20” on the other side.
No adverse events related to the lots involved in the recall have been reported, the FDA said. It also recommends that clinicians continue to prescribe metformin when clinically appropriate.
In late 2019, the FDA announced it had become aware of NDMA in some metformin products in other countries. The agency immediately began testing to determine whether the metformin in the U.S. supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types, which included recalls of hypertension and heartburn medications within the past 3 years.
In February 2020, the FDA reported that they hadn’t found NDMA levels that exceeded the acceptable daily intake. But starting in May 2020, voluntary recalls by, numerous manufacturers have been announced as levels of the compound exceeded that cutoff.
Two lots of metformin HCl extended-release tablets have been recalled by Viona Pharmaceuticals because unacceptable levels of nitrosodimethylamine (NDMA), a likely carcinogen, were found in the 750-mg tablets.
According to a June 11 alert from the Food and Drug Administration, the affected lot numbers are M915601 and M915602.
This generic product was made by Cadila Healthcare, Ahmedabad, India, in November 2019 with an expiration date of October 2021, and distributed throughout the United States. The pill is white to off-white, capsule-shaped, uncoated tablets, debossed with “Z”, “C” on one side and “20” on the other side.
No adverse events related to the lots involved in the recall have been reported, the FDA said. It also recommends that clinicians continue to prescribe metformin when clinically appropriate.
In late 2019, the FDA announced it had become aware of NDMA in some metformin products in other countries. The agency immediately began testing to determine whether the metformin in the U.S. supply was at risk, as part of the ongoing investigation into nitrosamine impurities across medication types, which included recalls of hypertension and heartburn medications within the past 3 years.
In February 2020, the FDA reported that they hadn’t found NDMA levels that exceeded the acceptable daily intake. But starting in May 2020, voluntary recalls by, numerous manufacturers have been announced as levels of the compound exceeded that cutoff.
FROM THE FOOD AND DRUG ADMINISTRATION
FDA clears next-generation DBS system for movement disorders
The SenSight Directional Lead System for DBS therapy combines two recent advancements: sensing capability that allows real-time monitoring of brain signals to optimize settings for stimulation, and a “directional lead” that enables steering of electric current for more precise targeting of stimulation through the electrode.
“Until now, sensing capability and directional leads have not been available in the same DBS system, so we have had to choose one technology or the other, based on the predicted needs of each patient,” neurosurgeon Kelly Foote, MD, who performed the first implant of the SenSight System at University of Florida (UF) Health, said in a news release.
“Now, by coupling this new directional lead with a pulse generator capable of brain sensing, we are excited to be able to offer our patients the synergistic benefits of both technologies,” added Dr. Foote, codirector of the Norman Fixel Institute for Neurological Diseases at UF Health.
Dr. Foote said DBS systems capable of adjusting therapeutic stimulation in response to continuously recorded brain signals may lead to better DBS outcomes with fewer adverse effects.
“Adding a directional lead to such a system will improve our ability to localize abnormal signals and enable us to steer current more effectively to areas in the brain where it is most beneficial,” Dr. Foote said.
“We are excited to see the clinical benefits that the new SenSight directional lead system will provide to patients and physicians in the U.S.,” added Mike Daly, vice president and general manager of brain modulation at Medtronic.
Medtronic’s SenSight directional lead DBS system received CE Mark approval in Europe in March.
A version of this article first appeared on Medscape.com.
The SenSight Directional Lead System for DBS therapy combines two recent advancements: sensing capability that allows real-time monitoring of brain signals to optimize settings for stimulation, and a “directional lead” that enables steering of electric current for more precise targeting of stimulation through the electrode.
“Until now, sensing capability and directional leads have not been available in the same DBS system, so we have had to choose one technology or the other, based on the predicted needs of each patient,” neurosurgeon Kelly Foote, MD, who performed the first implant of the SenSight System at University of Florida (UF) Health, said in a news release.
“Now, by coupling this new directional lead with a pulse generator capable of brain sensing, we are excited to be able to offer our patients the synergistic benefits of both technologies,” added Dr. Foote, codirector of the Norman Fixel Institute for Neurological Diseases at UF Health.
Dr. Foote said DBS systems capable of adjusting therapeutic stimulation in response to continuously recorded brain signals may lead to better DBS outcomes with fewer adverse effects.
“Adding a directional lead to such a system will improve our ability to localize abnormal signals and enable us to steer current more effectively to areas in the brain where it is most beneficial,” Dr. Foote said.
“We are excited to see the clinical benefits that the new SenSight directional lead system will provide to patients and physicians in the U.S.,” added Mike Daly, vice president and general manager of brain modulation at Medtronic.
Medtronic’s SenSight directional lead DBS system received CE Mark approval in Europe in March.
A version of this article first appeared on Medscape.com.
The SenSight Directional Lead System for DBS therapy combines two recent advancements: sensing capability that allows real-time monitoring of brain signals to optimize settings for stimulation, and a “directional lead” that enables steering of electric current for more precise targeting of stimulation through the electrode.
“Until now, sensing capability and directional leads have not been available in the same DBS system, so we have had to choose one technology or the other, based on the predicted needs of each patient,” neurosurgeon Kelly Foote, MD, who performed the first implant of the SenSight System at University of Florida (UF) Health, said in a news release.
“Now, by coupling this new directional lead with a pulse generator capable of brain sensing, we are excited to be able to offer our patients the synergistic benefits of both technologies,” added Dr. Foote, codirector of the Norman Fixel Institute for Neurological Diseases at UF Health.
Dr. Foote said DBS systems capable of adjusting therapeutic stimulation in response to continuously recorded brain signals may lead to better DBS outcomes with fewer adverse effects.
“Adding a directional lead to such a system will improve our ability to localize abnormal signals and enable us to steer current more effectively to areas in the brain where it is most beneficial,” Dr. Foote said.
“We are excited to see the clinical benefits that the new SenSight directional lead system will provide to patients and physicians in the U.S.,” added Mike Daly, vice president and general manager of brain modulation at Medtronic.
Medtronic’s SenSight directional lead DBS system received CE Mark approval in Europe in March.
A version of this article first appeared on Medscape.com.
FDA approves controversial Alzheimer’s drug aducanumab (Aduhelm)
In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.
In a company release Michel Vounatsos, Biogen’s Chief Executive Officer, said, “this historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.
Rocky road
The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.
As reported by this news organization, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.
However, in an about-face 7 months later, Biogen and Eisai announced that a new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.
Although ENGAGE still didn’t meet its primary endpoint, data from its new analysis “supported” the EMERGE findings, the drug companies said at the time.
However, 1 year later, a majority of the members of the FDA’s advisory panel were against the drug’s approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.
As reported by this news organization, a Viewpoint written by three of the committee members notes that results from the drug’s only large positive clinical trial fell short.
“There is no persuasive evidence to support approval of aducanumab at this time,” they write.
Groups such as Public Citizen’s Health Research Group not only agree with the Viewpoint’s authors, they also criticized the FDA for its collaboration with the drug’s manufacturers on briefing documents and more.
On April 1, Health Research Group members sent a letter to the U.S. Secretary of Health and Human Services requesting the temporary suspension of the FDA’s neuroscience chief, Bill Dunn, MD, because of his role in supervising the collaboration.
Alzheimer association weighs in
The Alzheimer’s Association has been a proponent of the drug throughout its development.
Ahead of today’s news, the organization noted in a statement that a decision to approve “would be historic” because it would make aducanumab “the first drug to slow Alzheimer’s disease” and would mark the beginning of a new future for AD treatments.
“The Alzheimer’s Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference” for patients with AD, it said.
Kristen Clifford, chief program officer for the Alzheimer’s Association, said in an interview at the time that approval would be considered a “victory” for patients with AD and for the field overall.
“For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life,” Clifford said.
“If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer’s and their families,” she added.
Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. “This treatment would encourage earlier diagnosis of the disease,” she said.
In a new statement released just after approval for aducanumab was announced, the organization said that today’s news is a win-win for all patients with AD and their families.
A version of this article first appeared on Medscape.com.
In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.
In a company release Michel Vounatsos, Biogen’s Chief Executive Officer, said, “this historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.
Rocky road
The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.
As reported by this news organization, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.
However, in an about-face 7 months later, Biogen and Eisai announced that a new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.
Although ENGAGE still didn’t meet its primary endpoint, data from its new analysis “supported” the EMERGE findings, the drug companies said at the time.
However, 1 year later, a majority of the members of the FDA’s advisory panel were against the drug’s approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.
As reported by this news organization, a Viewpoint written by three of the committee members notes that results from the drug’s only large positive clinical trial fell short.
“There is no persuasive evidence to support approval of aducanumab at this time,” they write.
Groups such as Public Citizen’s Health Research Group not only agree with the Viewpoint’s authors, they also criticized the FDA for its collaboration with the drug’s manufacturers on briefing documents and more.
On April 1, Health Research Group members sent a letter to the U.S. Secretary of Health and Human Services requesting the temporary suspension of the FDA’s neuroscience chief, Bill Dunn, MD, because of his role in supervising the collaboration.
Alzheimer association weighs in
The Alzheimer’s Association has been a proponent of the drug throughout its development.
Ahead of today’s news, the organization noted in a statement that a decision to approve “would be historic” because it would make aducanumab “the first drug to slow Alzheimer’s disease” and would mark the beginning of a new future for AD treatments.
“The Alzheimer’s Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference” for patients with AD, it said.
Kristen Clifford, chief program officer for the Alzheimer’s Association, said in an interview at the time that approval would be considered a “victory” for patients with AD and for the field overall.
“For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life,” Clifford said.
“If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer’s and their families,” she added.
Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. “This treatment would encourage earlier diagnosis of the disease,” she said.
In a new statement released just after approval for aducanumab was announced, the organization said that today’s news is a win-win for all patients with AD and their families.
A version of this article first appeared on Medscape.com.
In November, the Peripheral and Central Nervous System Drugs Advisory Committee voted eight to one against approving the drug because, based on clinical trial results, evidence of efficacy was not strong enough. Two other members said they were uncertain on the issue of efficacy.
In a company release Michel Vounatsos, Biogen’s Chief Executive Officer, said, “this historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come.
Rocky road
The road to approval has been extremely rocky for aducanumab, an anti-amyloid-beta human monoclonal antibody, previously known as BIIB037.
As reported by this news organization, two phase 3 trials evaluating the drug were initially scrapped in March 2019 because of interim futility analysis. At the time, Biogen released a statement saying that aducanumab was unlikely to meet primary endpoints in the ENGAGE and EMERGE randomized controlled trials.
However, in an about-face 7 months later, Biogen and Eisai announced that a new analysis showed the drug met its primary endpoint of reduction in clinical decline, including cognition and function, in the EMERGE trial.
Although ENGAGE still didn’t meet its primary endpoint, data from its new analysis “supported” the EMERGE findings, the drug companies said at the time.
However, 1 year later, a majority of the members of the FDA’s advisory panel were against the drug’s approval. Details of that decision were published online March 30 in the Journal of the American Medical Association.
As reported by this news organization, a Viewpoint written by three of the committee members notes that results from the drug’s only large positive clinical trial fell short.
“There is no persuasive evidence to support approval of aducanumab at this time,” they write.
Groups such as Public Citizen’s Health Research Group not only agree with the Viewpoint’s authors, they also criticized the FDA for its collaboration with the drug’s manufacturers on briefing documents and more.
On April 1, Health Research Group members sent a letter to the U.S. Secretary of Health and Human Services requesting the temporary suspension of the FDA’s neuroscience chief, Bill Dunn, MD, because of his role in supervising the collaboration.
Alzheimer association weighs in
The Alzheimer’s Association has been a proponent of the drug throughout its development.
Ahead of today’s news, the organization noted in a statement that a decision to approve “would be historic” because it would make aducanumab “the first drug to slow Alzheimer’s disease” and would mark the beginning of a new future for AD treatments.
“The Alzheimer’s Association urgently supports FDA approval of the treatment based on clinical trial results that showed a 22% reduction in cognitive and function decline — something that could make a meaningful difference” for patients with AD, it said.
Kristen Clifford, chief program officer for the Alzheimer’s Association, said in an interview at the time that approval would be considered a “victory” for patients with AD and for the field overall.
“For individuals who would potentially be eligible for the treatment, this drug could mean more quality time. Slowing decline, particularly in early diagnosis, could add weeks or months or maybe even years of active life,” Clifford said.
“If approved, this would really be a landmark moment. And it could provide hope for those living with Alzheimer’s and their families,” she added.
Clifford noted that approval of this type of drug would also underscore the importance of early detection for AD. “This treatment would encourage earlier diagnosis of the disease,” she said.
In a new statement released just after approval for aducanumab was announced, the organization said that today’s news is a win-win for all patients with AD and their families.
A version of this article first appeared on Medscape.com.
FDA approves ‘game changer’ semaglutide for weight loss
The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.
Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m2) or are overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbidity.
Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.
Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.
This weight-loss drug is currently under review by the European Medicines Agency.
Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.
‘Game changer’ drug tested in STEP clinical trial program
The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.
The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.
As previously reported by this news organization, all trials were in adults with overweight or obesity:
- was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
- was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
- was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
- was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).
In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.
The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.
The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.
A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”
“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
Welcome Addition, But Will Insurance Coverage, Price Thwart Access?
Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”
The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.
And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.
Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.
However, insurance coverage and price could block uptake.
“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”
“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.
“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”
However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”
“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.
Lower-dose injectable and pill already approved for diabetes
Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.
The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.
And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
CVOT and oral format trials for obesity on the horizon
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.
And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.
A version of this article first appeared on Medscape.com.
This article was updated 6/7/21.
The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.
Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m2) or are overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbidity.
Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.
Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.
This weight-loss drug is currently under review by the European Medicines Agency.
Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.
‘Game changer’ drug tested in STEP clinical trial program
The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.
The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.
As previously reported by this news organization, all trials were in adults with overweight or obesity:
- was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
- was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
- was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
- was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).
In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.
The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.
The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.
A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”
“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
Welcome Addition, But Will Insurance Coverage, Price Thwart Access?
Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”
The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.
And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.
Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.
However, insurance coverage and price could block uptake.
“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”
“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.
“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”
However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”
“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.
Lower-dose injectable and pill already approved for diabetes
Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.
The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.
And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
CVOT and oral format trials for obesity on the horizon
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.
And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.
A version of this article first appeared on Medscape.com.
This article was updated 6/7/21.
The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.
Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m2) or are overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbidity.
Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.
Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.
This weight-loss drug is currently under review by the European Medicines Agency.
Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.
‘Game changer’ drug tested in STEP clinical trial program
The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.
The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.
As previously reported by this news organization, all trials were in adults with overweight or obesity:
- was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
- was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
- was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
- was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).
In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.
The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.
The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.
A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”
“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
Welcome Addition, But Will Insurance Coverage, Price Thwart Access?
Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”
The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.
And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.
Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.
However, insurance coverage and price could block uptake.
“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”
“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.
“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”
However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”
“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.
Lower-dose injectable and pill already approved for diabetes
Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.
The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.
And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
CVOT and oral format trials for obesity on the horizon
The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.
And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.
A version of this article first appeared on Medscape.com.
This article was updated 6/7/21.
Medtronic yanks Heartware VAD, calls for halt to new implants
Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.
“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.
There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.
Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.
Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.
“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”
Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.
The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.
In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).
“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”
For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”
Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: [email protected].
Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.
Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.
Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.
A version of this article first appeared on Medscape.com.
Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.
“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.
There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.
Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.
Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.
“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”
Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.
The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.
In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).
“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”
For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”
Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: [email protected].
Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.
Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.
Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.
A version of this article first appeared on Medscape.com.
Medtronic has stopped the sale of its Heartware Ventricular Assist Device (HVAD) system and is advising that physicians cease implanting the device because problems with an internal pump can lead to death or serious injuries.
“There is an increased risk of neurological adverse events and mortality associated with the internal pump,” the U.S. Food and Drug Administration announced today.
There is also a potential for the internal pump to stop, and there may be delay or failure to restart. “Both problems may lead to death or serious injuries,” the agency said.
Between January 2009 and April 22, 2021, Medtronic received a total of 106 complaints involving delay or failure to restart with the HVAD pump. Of these, 26 complaints involved HVAD devices operating under normal conditions (dual stator mode) and 80 involved devices operating in a back-up mode (single stator mode) that allows for continued pump function if electrical continuity between the pump and controller is interrupted.
Of the 26 complaints that occurred under normal conditions, four resulted in patient death and five led to urgent explant. Of the 80 complaints that occurred in single stator mode, 10 deaths and eight explants were reported to Medtronic, according to an urgent medical device communication letter issued by the company today.
“Considering these findings and given the availability of alternative devices such as the Abbott HeartMate 3, Medtronic has made the decision to stop the distribution and sale of the HVAD System,” the letter says. “Medtronic advises that there be no further implantations of the HVAD System.”
Medtronic undertook a previous recall of the Heartware HVAD system in February, focusing on batteries, power, datalink cables, and other peripheral equipment, because of the “risk of wear and tear of the connector plugs (power sources, data cable, and alarm adapter), which could cause damage to the controller port metal pins (for example, bent pins).” The FDA deemed that recall Class I, the most serious category of safety alert, in April.
The company noted that patients who currently have an HVAD implant “may require support for many years,” and that it is moving as quickly as possible to create a plan to guide the ongoing support for patients, caregivers, and health care professionals.
In response to the restart failure issue and evolving data about neurologic risks associated with the HVAD pump, Medtronic said it engaged an Independent Practitioner Quality Panel (IPQP), composed of cardiologists, surgeons, and VAD coordinators, to advise on recommendations for appropriate patient management. Based on information collected to date and IPQP input, Medtronic is recommending that physicians continue following best clinical practices and manage patients implanted with the HVAD pump according to the recommendations in the Instructions for Use (IFU).
“Prophylactic explant of the HVAD™ device is not recommended, as risks associated with explantation may outweigh the potential benefits,” the letter says. “The decision regarding explant and exchange of the HVAD™ pump should be made by physicians on a case-by-case basis, considering the patient’s clinical condition and surgical risks. If a physician determines that pump exchange is appropriate, we recommend exchanging to an alternative commercial LVAD.”
For patients in urgent need of an LVAD, Medtronic said physicians should use an alternative commercial LVAD or, if one is not available, that “a Patient Information form is required to be completed by you and your patient to acknowledge the risks of an HVAD implant prior to implanting your HVAD inventory.”
Today’s letter also provides recommendations on blood pressure management goals and anticoagulation. For any other questions or concerns, physicians should contact the Medtronic Office of Medical Affairs at: [email protected].
Medtronic issued another urgent letter in December 2020, warning physicians that a subset of HVAD devices included an internal pump component from three specific lots that increased the risk for restart failure. At that time, the company had not been able to pinpoint a root cause of the pump restart failure.
Consistent with the December 2020 notice, the rate of failure among pumps outside of the subset of three specific lots currently remains at about 0.4%, according to today’s notice.
Although Medtronic has identified the root cause and mitigations for pumps within the three specific lots, it has not been able to identify a root cause of the other restart failures reported with the HVAD pumps, the company said.
A version of this article first appeared on Medscape.com.
FDA approves ibrexafungerp for vaginal yeast infection
Ibrexafungerp is the first drug approved in a new antifungal class for vulvovaginal candidiasis (VVC) in more than 20 years, the drug’s manufacturer Scynexis said in a press release. It becomes the first and only nonazole treatment for vaginal yeast infections.
The biotechnology company said approval came after positive results from two phase 3 studies in which oral ibrexafungerp demonstrated efficacy and tolerability. The most common reactions observed in clinical trials were diarrhea, nausea, abdominal pain, dizziness, and vomiting.
There are few other treatments for vaginal yeast infections, which is the second most common cause of vaginitis. Those previously approved agents include several topical azole antifungals and oral fluconazole (Diflucan), which, Scynexis said, is the only other orally administered antifungal approved for the treatment of VVC in the United States and has accounted for over more than 90% of prescriptions written for the condition each year.
However, the company noted, oral fluconazole reports a 55% therapeutic cure rate on its label, which now also includes warnings of potential fetal harm, demonstrating the need for new oral options.
The new drug may not fill that need for pregnant women, however, as the company noted that ibrexafungerp should not be used during pregnancy, and administration during pregnancy “may cause fetal harm based on animal studies.”
Because of possible teratogenic effects, the company advised clinicians to verify pregnancy status in females of reproductive potential before prescribing ibrexafungerp and advises effective contraception during treatment.
VVC can come with substantial morbidity, including genital pain, itching and burning, reduced sexual pleasure, and psychological distress.
David Angulo, MD, chief medical officer for Scynexis, said in a statement the tablets brings new benefits.
Dr. Angulo said the drug “has a differentiated fungicidal mechanism of action that kills a broad range of Candida species, including azole-resistant strains. We are working on completing our CANDLE study investigating ibrexafungerp for the prevention of recurrent VVC and expect we will be submitting a supplemental NDA [new drug application] in the first half of 2022.”
Scynexis said it partnered with Amplity Health, a Pennsylvania-based pharmaceutical company, to support U.S. marketing of the drug. The commercial launch will follow the approval.
Ibrexafungerp was granted approval through both the FDA’s Qualified Infectious Disease Product and Fast Track designations. It is expected to be marketed exclusively in the United States for 10 years.
A version of this article first appeared on Medscape.com.
Ibrexafungerp is the first drug approved in a new antifungal class for vulvovaginal candidiasis (VVC) in more than 20 years, the drug’s manufacturer Scynexis said in a press release. It becomes the first and only nonazole treatment for vaginal yeast infections.
The biotechnology company said approval came after positive results from two phase 3 studies in which oral ibrexafungerp demonstrated efficacy and tolerability. The most common reactions observed in clinical trials were diarrhea, nausea, abdominal pain, dizziness, and vomiting.
There are few other treatments for vaginal yeast infections, which is the second most common cause of vaginitis. Those previously approved agents include several topical azole antifungals and oral fluconazole (Diflucan), which, Scynexis said, is the only other orally administered antifungal approved for the treatment of VVC in the United States and has accounted for over more than 90% of prescriptions written for the condition each year.
However, the company noted, oral fluconazole reports a 55% therapeutic cure rate on its label, which now also includes warnings of potential fetal harm, demonstrating the need for new oral options.
The new drug may not fill that need for pregnant women, however, as the company noted that ibrexafungerp should not be used during pregnancy, and administration during pregnancy “may cause fetal harm based on animal studies.”
Because of possible teratogenic effects, the company advised clinicians to verify pregnancy status in females of reproductive potential before prescribing ibrexafungerp and advises effective contraception during treatment.
VVC can come with substantial morbidity, including genital pain, itching and burning, reduced sexual pleasure, and psychological distress.
David Angulo, MD, chief medical officer for Scynexis, said in a statement the tablets brings new benefits.
Dr. Angulo said the drug “has a differentiated fungicidal mechanism of action that kills a broad range of Candida species, including azole-resistant strains. We are working on completing our CANDLE study investigating ibrexafungerp for the prevention of recurrent VVC and expect we will be submitting a supplemental NDA [new drug application] in the first half of 2022.”
Scynexis said it partnered with Amplity Health, a Pennsylvania-based pharmaceutical company, to support U.S. marketing of the drug. The commercial launch will follow the approval.
Ibrexafungerp was granted approval through both the FDA’s Qualified Infectious Disease Product and Fast Track designations. It is expected to be marketed exclusively in the United States for 10 years.
A version of this article first appeared on Medscape.com.
Ibrexafungerp is the first drug approved in a new antifungal class for vulvovaginal candidiasis (VVC) in more than 20 years, the drug’s manufacturer Scynexis said in a press release. It becomes the first and only nonazole treatment for vaginal yeast infections.
The biotechnology company said approval came after positive results from two phase 3 studies in which oral ibrexafungerp demonstrated efficacy and tolerability. The most common reactions observed in clinical trials were diarrhea, nausea, abdominal pain, dizziness, and vomiting.
There are few other treatments for vaginal yeast infections, which is the second most common cause of vaginitis. Those previously approved agents include several topical azole antifungals and oral fluconazole (Diflucan), which, Scynexis said, is the only other orally administered antifungal approved for the treatment of VVC in the United States and has accounted for over more than 90% of prescriptions written for the condition each year.
However, the company noted, oral fluconazole reports a 55% therapeutic cure rate on its label, which now also includes warnings of potential fetal harm, demonstrating the need for new oral options.
The new drug may not fill that need for pregnant women, however, as the company noted that ibrexafungerp should not be used during pregnancy, and administration during pregnancy “may cause fetal harm based on animal studies.”
Because of possible teratogenic effects, the company advised clinicians to verify pregnancy status in females of reproductive potential before prescribing ibrexafungerp and advises effective contraception during treatment.
VVC can come with substantial morbidity, including genital pain, itching and burning, reduced sexual pleasure, and psychological distress.
David Angulo, MD, chief medical officer for Scynexis, said in a statement the tablets brings new benefits.
Dr. Angulo said the drug “has a differentiated fungicidal mechanism of action that kills a broad range of Candida species, including azole-resistant strains. We are working on completing our CANDLE study investigating ibrexafungerp for the prevention of recurrent VVC and expect we will be submitting a supplemental NDA [new drug application] in the first half of 2022.”
Scynexis said it partnered with Amplity Health, a Pennsylvania-based pharmaceutical company, to support U.S. marketing of the drug. The commercial launch will follow the approval.
Ibrexafungerp was granted approval through both the FDA’s Qualified Infectious Disease Product and Fast Track designations. It is expected to be marketed exclusively in the United States for 10 years.
A version of this article first appeared on Medscape.com.
FDA approves diagnostic device for autism spectrum disorder
The Food and Drug Administration has approved marketing for a device that will help diagnose autism spectrum disorder (ASD) in children between the ages of 18 months and 5 years old who exhibit potential symptoms.
Cognoa ASD Diagnosis Aid is a machine learning–based software program that receives information from parents or caregivers, video analysts, and health care providers to assist physicians in evaluating whether a child is at risk of having autism.
Autism is a developmental disorder that can cause social, communication, and behavioral challenges, according to the Centers for Disease Control and Prevention. The disorder affects about 1 in 54 children. The disorder is difficult to diagnose because there isn’t a medical test to diagnose the it. Instead, physicians have to look at a child’s developmental history and behavior to make a diagnosis.
Many children are not diagnosed with ASD until later in childhood, which in some cases delays treatment and early intervention. ASD may be detected as early as 18 months, but the average age of diagnosis for ASD is 4.3 years, according to the FDA.
“[ASD] can delay a child’s physical, cognitive, and social development, including motor skill development, learning, communication, and interacting with others. The earlier ASD can be diagnosed, the more quickly intervention strategies and appropriate therapies can begin,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement. “Today’s marketing authorization provides a new tool for helping diagnose children with ASD.”
The safety and efficacy of the Cognoa ASD Diagnosis Aid was assessed in a study of 425 patients between the ages of 18 months and 5 years old. For the study, researchers compared the diagnostic assessments made by the device to those made by a panel of clinical experts who used the current standard ASD diagnostic process. The device diagnosed 32% of the children with either a “Positive for ASD” or a “Negative for ASD” result. Researchers found that the device matched the panel’s conclusions for 81% of the patients who received a positive diagnosis. For those who received a negative diagnosis, the device matched the panel’s conclusions for 98% of the patients. In addition, the device made an accurate ASD determination in 98.4% of patients with the condition and in 78.9% of patients without the condition.
Cognoa ASD Diagnosis Aid has three main components. One component includes a mobile app for caregivers to answer questions about the child’s behavioral problems and to upload videos of the child. The next component is a video analysis portal for specialists to view and analyze uploaded videos of patients. Another component is a portal for health care providers that allows them to enter answers to preloaded questions about behavior problems, track the information provided by parents, and review a report of the results.
After the machine learning–based device processes the information provided by parents and health care providers, it reports either a positive or a negative diagnosis. If there is insufficient information to make either a positive or a negative diagnosis, the ASD Diagnostic AID will report that no result can be generated.
Some of the risks associated with this device include misdiagnosis and delayed diagnosis of ASD because of a false-positive or false-negative result, or when no result is generated. Researchers said a false-positive result occurred in 15 out of 303 study subjects without ASD and a false-negative result occurred in 1 out of 122 study subjects with ASD.
The FDA emphasized that the device is indicated to aid physicians in the process of diagnosing ASD in children. This means it shouldn’t be treated as a standalone diagnostic device, but as an adjunct to the diagnostic process.
The Food and Drug Administration has approved marketing for a device that will help diagnose autism spectrum disorder (ASD) in children between the ages of 18 months and 5 years old who exhibit potential symptoms.
Cognoa ASD Diagnosis Aid is a machine learning–based software program that receives information from parents or caregivers, video analysts, and health care providers to assist physicians in evaluating whether a child is at risk of having autism.
Autism is a developmental disorder that can cause social, communication, and behavioral challenges, according to the Centers for Disease Control and Prevention. The disorder affects about 1 in 54 children. The disorder is difficult to diagnose because there isn’t a medical test to diagnose the it. Instead, physicians have to look at a child’s developmental history and behavior to make a diagnosis.
Many children are not diagnosed with ASD until later in childhood, which in some cases delays treatment and early intervention. ASD may be detected as early as 18 months, but the average age of diagnosis for ASD is 4.3 years, according to the FDA.
“[ASD] can delay a child’s physical, cognitive, and social development, including motor skill development, learning, communication, and interacting with others. The earlier ASD can be diagnosed, the more quickly intervention strategies and appropriate therapies can begin,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement. “Today’s marketing authorization provides a new tool for helping diagnose children with ASD.”
The safety and efficacy of the Cognoa ASD Diagnosis Aid was assessed in a study of 425 patients between the ages of 18 months and 5 years old. For the study, researchers compared the diagnostic assessments made by the device to those made by a panel of clinical experts who used the current standard ASD diagnostic process. The device diagnosed 32% of the children with either a “Positive for ASD” or a “Negative for ASD” result. Researchers found that the device matched the panel’s conclusions for 81% of the patients who received a positive diagnosis. For those who received a negative diagnosis, the device matched the panel’s conclusions for 98% of the patients. In addition, the device made an accurate ASD determination in 98.4% of patients with the condition and in 78.9% of patients without the condition.
Cognoa ASD Diagnosis Aid has three main components. One component includes a mobile app for caregivers to answer questions about the child’s behavioral problems and to upload videos of the child. The next component is a video analysis portal for specialists to view and analyze uploaded videos of patients. Another component is a portal for health care providers that allows them to enter answers to preloaded questions about behavior problems, track the information provided by parents, and review a report of the results.
After the machine learning–based device processes the information provided by parents and health care providers, it reports either a positive or a negative diagnosis. If there is insufficient information to make either a positive or a negative diagnosis, the ASD Diagnostic AID will report that no result can be generated.
Some of the risks associated with this device include misdiagnosis and delayed diagnosis of ASD because of a false-positive or false-negative result, or when no result is generated. Researchers said a false-positive result occurred in 15 out of 303 study subjects without ASD and a false-negative result occurred in 1 out of 122 study subjects with ASD.
The FDA emphasized that the device is indicated to aid physicians in the process of diagnosing ASD in children. This means it shouldn’t be treated as a standalone diagnostic device, but as an adjunct to the diagnostic process.
The Food and Drug Administration has approved marketing for a device that will help diagnose autism spectrum disorder (ASD) in children between the ages of 18 months and 5 years old who exhibit potential symptoms.
Cognoa ASD Diagnosis Aid is a machine learning–based software program that receives information from parents or caregivers, video analysts, and health care providers to assist physicians in evaluating whether a child is at risk of having autism.
Autism is a developmental disorder that can cause social, communication, and behavioral challenges, according to the Centers for Disease Control and Prevention. The disorder affects about 1 in 54 children. The disorder is difficult to diagnose because there isn’t a medical test to diagnose the it. Instead, physicians have to look at a child’s developmental history and behavior to make a diagnosis.
Many children are not diagnosed with ASD until later in childhood, which in some cases delays treatment and early intervention. ASD may be detected as early as 18 months, but the average age of diagnosis for ASD is 4.3 years, according to the FDA.
“[ASD] can delay a child’s physical, cognitive, and social development, including motor skill development, learning, communication, and interacting with others. The earlier ASD can be diagnosed, the more quickly intervention strategies and appropriate therapies can begin,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a statement. “Today’s marketing authorization provides a new tool for helping diagnose children with ASD.”
The safety and efficacy of the Cognoa ASD Diagnosis Aid was assessed in a study of 425 patients between the ages of 18 months and 5 years old. For the study, researchers compared the diagnostic assessments made by the device to those made by a panel of clinical experts who used the current standard ASD diagnostic process. The device diagnosed 32% of the children with either a “Positive for ASD” or a “Negative for ASD” result. Researchers found that the device matched the panel’s conclusions for 81% of the patients who received a positive diagnosis. For those who received a negative diagnosis, the device matched the panel’s conclusions for 98% of the patients. In addition, the device made an accurate ASD determination in 98.4% of patients with the condition and in 78.9% of patients without the condition.
Cognoa ASD Diagnosis Aid has three main components. One component includes a mobile app for caregivers to answer questions about the child’s behavioral problems and to upload videos of the child. The next component is a video analysis portal for specialists to view and analyze uploaded videos of patients. Another component is a portal for health care providers that allows them to enter answers to preloaded questions about behavior problems, track the information provided by parents, and review a report of the results.
After the machine learning–based device processes the information provided by parents and health care providers, it reports either a positive or a negative diagnosis. If there is insufficient information to make either a positive or a negative diagnosis, the ASD Diagnostic AID will report that no result can be generated.
Some of the risks associated with this device include misdiagnosis and delayed diagnosis of ASD because of a false-positive or false-negative result, or when no result is generated. Researchers said a false-positive result occurred in 15 out of 303 study subjects without ASD and a false-negative result occurred in 1 out of 122 study subjects with ASD.
The FDA emphasized that the device is indicated to aid physicians in the process of diagnosing ASD in children. This means it shouldn’t be treated as a standalone diagnostic device, but as an adjunct to the diagnostic process.
CDC: New botulism guidelines focus on mass casualty events
Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose.
The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.
In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”
While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.
Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
Diagnosis
Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.
Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).
Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.
Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.
With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.
Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”
It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.
Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
Treatment
Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.
Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.
While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.
Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.
Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.
A version of this article first appeared on Medscape.com.
Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose.
The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.
In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”
While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.
Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
Diagnosis
Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.
Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).
Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.
Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.
With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.
Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”
It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.
Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
Treatment
Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.
Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.
While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.
Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.
Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.
A version of this article first appeared on Medscape.com.
Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose.
The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.
In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.
Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”
While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.
Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
Diagnosis
Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.
Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).
Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.
Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.
With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.
Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”
It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.
Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
Treatment
Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.
Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.
While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.
Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.
Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.
A version of this article first appeared on Medscape.com.
FDA okays new drug option for schizophrenia, bipolar I disorder
The U.S. Food and Drug Administration has approved a once-daily oral medication, which is a combination of olanzapine and samidorphan (Lybalvi, Alkermes), for the treatment of schizophrenia and bipolar I disorder.
The drug is approved for the treatment of adults with schizophrenia and for adults with bipolar I disorder as a maintenance monotherapy or to treat acute manic or mixed episodes, as either monotherapy or an adjunct to lithium or valproate.
An atypical antipsychotic, the drug is a combination of olanzapine, an established antipsychotic medication, and samidorphan, a new chemical entity.
“Schizophrenia and bipolar I disorder are complex, chronic diseases, and there remains a persistent need for new medications with proven efficacy and safety. Olanzapine, a highly efficacious atypical antipsychotic, is associated with significant side effects, including weight gain that may impact patients’ treatment experiences and limit its use. With the efficacy of olanzapine and evidence of less weight gain in patients with schizophrenia, Lybalvi brings a welcome new addition to our medication arsenal,” René S. Kahn, MD, PhD, Esther and Joseph Klingenstein professor & chair, department of psychiatry and Behavioral Health System at the Icahn School of Medicine at Mount Sinai, New York, said in a company press release.
In a clinical development program, the drug demonstrated antipsychotic efficacy, safety, and tolerability, including significantly less weight gain than olanzapine in patients with schizophrenia in the ENLIGHTEN-2 study.
The FDA approved Lybalvi under the 505(b)(2) regulatory pathway based on data from 27 clinical studies, including 18 studies evaluating Lybalvi and nine studies evaluating samidorphan alone and the FDA’s findings of the safety and effectiveness of olanzapine in the treatment of bipolar I disorder and schizophrenia. Data suggest that olanzapine-associated weight gain is disease independent, the company reports.
“People living with schizophrenia or bipolar I disorder must evaluate both efficacy and tolerability when making treatment decisions,” Paul Gionfriddo, president and CEO of Mental Health America, said in the same company press release. “We are grateful that companies like Alkermes are driven to continue developing new treatment options in psychiatry that seek to address unmet needs of our community, and we applaud the FDA for considering the experiences of individuals living with these conditions.”
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved a once-daily oral medication, which is a combination of olanzapine and samidorphan (Lybalvi, Alkermes), for the treatment of schizophrenia and bipolar I disorder.
The drug is approved for the treatment of adults with schizophrenia and for adults with bipolar I disorder as a maintenance monotherapy or to treat acute manic or mixed episodes, as either monotherapy or an adjunct to lithium or valproate.
An atypical antipsychotic, the drug is a combination of olanzapine, an established antipsychotic medication, and samidorphan, a new chemical entity.
“Schizophrenia and bipolar I disorder are complex, chronic diseases, and there remains a persistent need for new medications with proven efficacy and safety. Olanzapine, a highly efficacious atypical antipsychotic, is associated with significant side effects, including weight gain that may impact patients’ treatment experiences and limit its use. With the efficacy of olanzapine and evidence of less weight gain in patients with schizophrenia, Lybalvi brings a welcome new addition to our medication arsenal,” René S. Kahn, MD, PhD, Esther and Joseph Klingenstein professor & chair, department of psychiatry and Behavioral Health System at the Icahn School of Medicine at Mount Sinai, New York, said in a company press release.
In a clinical development program, the drug demonstrated antipsychotic efficacy, safety, and tolerability, including significantly less weight gain than olanzapine in patients with schizophrenia in the ENLIGHTEN-2 study.
The FDA approved Lybalvi under the 505(b)(2) regulatory pathway based on data from 27 clinical studies, including 18 studies evaluating Lybalvi and nine studies evaluating samidorphan alone and the FDA’s findings of the safety and effectiveness of olanzapine in the treatment of bipolar I disorder and schizophrenia. Data suggest that olanzapine-associated weight gain is disease independent, the company reports.
“People living with schizophrenia or bipolar I disorder must evaluate both efficacy and tolerability when making treatment decisions,” Paul Gionfriddo, president and CEO of Mental Health America, said in the same company press release. “We are grateful that companies like Alkermes are driven to continue developing new treatment options in psychiatry that seek to address unmet needs of our community, and we applaud the FDA for considering the experiences of individuals living with these conditions.”
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved a once-daily oral medication, which is a combination of olanzapine and samidorphan (Lybalvi, Alkermes), for the treatment of schizophrenia and bipolar I disorder.
The drug is approved for the treatment of adults with schizophrenia and for adults with bipolar I disorder as a maintenance monotherapy or to treat acute manic or mixed episodes, as either monotherapy or an adjunct to lithium or valproate.
An atypical antipsychotic, the drug is a combination of olanzapine, an established antipsychotic medication, and samidorphan, a new chemical entity.
“Schizophrenia and bipolar I disorder are complex, chronic diseases, and there remains a persistent need for new medications with proven efficacy and safety. Olanzapine, a highly efficacious atypical antipsychotic, is associated with significant side effects, including weight gain that may impact patients’ treatment experiences and limit its use. With the efficacy of olanzapine and evidence of less weight gain in patients with schizophrenia, Lybalvi brings a welcome new addition to our medication arsenal,” René S. Kahn, MD, PhD, Esther and Joseph Klingenstein professor & chair, department of psychiatry and Behavioral Health System at the Icahn School of Medicine at Mount Sinai, New York, said in a company press release.
In a clinical development program, the drug demonstrated antipsychotic efficacy, safety, and tolerability, including significantly less weight gain than olanzapine in patients with schizophrenia in the ENLIGHTEN-2 study.
The FDA approved Lybalvi under the 505(b)(2) regulatory pathway based on data from 27 clinical studies, including 18 studies evaluating Lybalvi and nine studies evaluating samidorphan alone and the FDA’s findings of the safety and effectiveness of olanzapine in the treatment of bipolar I disorder and schizophrenia. Data suggest that olanzapine-associated weight gain is disease independent, the company reports.
“People living with schizophrenia or bipolar I disorder must evaluate both efficacy and tolerability when making treatment decisions,” Paul Gionfriddo, president and CEO of Mental Health America, said in the same company press release. “We are grateful that companies like Alkermes are driven to continue developing new treatment options in psychiatry that seek to address unmet needs of our community, and we applaud the FDA for considering the experiences of individuals living with these conditions.”
A version of this article first appeared on Medscape.com.
First drug for lung cancer with KRAS mutation gains FDA approval
The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.
KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.
The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.
It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.
“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.
Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.
“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
Details of clinical data
This is an accelerated approval based on response rate data.
The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.
The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.
Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.
The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.
Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
Companion diagnostic tests also approved
Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.
A version of this article first appeared on Medscape.com.
The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.
KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.
The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.
It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.
“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.
Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.
“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
Details of clinical data
This is an accelerated approval based on response rate data.
The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.
The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.
Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.
The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.
Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
Companion diagnostic tests also approved
Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.
A version of this article first appeared on Medscape.com.
The first drug to target KRAS mutations in non–small cell lung cancer (NSCLC) has been approved by the Food and Drug Administration.
KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time they appeared to be resistant to drug therapy.
The new drug, sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations.
It is considered to be something of a breakthrough in cancer research. When clinical data on the new drug (from 126 patients) were presented last year at the World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.
“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob T. Li, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, said at the time.
Now, in a press release from the manufacturer, Amgen, he said: “Sotorasib represents a major advancement in oncology and changes the treatment paradigm for patients with KRAS G12C-mutated non–small cell lung cancer.
“Patients with non–small cell lung cancer who have progressed beyond first-line treatment face a poor prognosis and have limited treatment options available to them. Sotorasib delivers a new option for these patients, and it is the first KRAS-targeted therapy to be approved after nearly four decades of research,” he added.
Details of clinical data
This is an accelerated approval based on response rate data.
The FDA notes that the clinical data come from a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.
The major outcome measured was overall response rate (ORR), which was 36%. Of the patients who responded, 58% had a duration of response of 6 months or longer.
Sotorasib was approved at a dose of 960 mg, and this dose was based on available clinical data as well as pharmacokinetic and pharmacodynamic modeling, the FDA noted. As part of the evaluation for this accelerated approval, the agency is requiring a postmarketing trial to investigate whether a lower dose will have a similar clinical effect.
The most common side effects include diarrhea, musculoskeletal pain, nausea, fatigue, liver damage, and cough. Sotorasib should not be used if patients develop symptoms of interstitial lung disease, and should be permanently discontinued if interstitial lung disease is confirmed.
Patients on sotorasib should have liver function tests prior to starting and while taking the drug; if liver damage develops, the drug should be stopped or the dose reduced. Patients should avoid taking acid-reducing agents, drugs that induce or are substrates for certain enzymes in the liver, and drugs that are substrates of P-glycoprotein (P-gp).
Companion diagnostic tests also approved
Along with the new drug, the FDA approved two companion diagnostic tests – the QIAGEN therascreen KRAS RGQ PCR kit (approval granted to QIAGEN GmbH) for analyzing tumor tissue and the Guardant360 CDx (approval granted to Guardant Health) for analyzing plasma specimens to determine if the KRAS G12C mutation is present. The agency notes that if the plasma test comes back negative, the patient’s tumor tissue should be tested.
A version of this article first appeared on Medscape.com.