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Peanut contamination risk prompts Promacta recall
Novartis has recalled three lots of 12.5-mg eltrombopag (Promacta) for oral suspension following discovery of possible contamination with peanut flour at a third-party manufacturing site.
Tablets at doses of 12.5 mg, 25 mg, 50 mg, and 75 mg are unaffected by this recall because they are not manufactured in the same facility. The recalled lots of medication were distributed between January and April 2019, but so far, Novartis has not received any reports of adverse events related to the recall.
Oral suspension of eltrombopag is indicated for certain patients with chronic immune thrombocytopenia, hepatitis C–associated thrombocytopenia, and severe aplastic anemia.
More information on the recalled lots and instructions on how to return the product can be found in the full announcement, which is also available through the Food and Drug Administration website.
Novartis has recalled three lots of 12.5-mg eltrombopag (Promacta) for oral suspension following discovery of possible contamination with peanut flour at a third-party manufacturing site.
Tablets at doses of 12.5 mg, 25 mg, 50 mg, and 75 mg are unaffected by this recall because they are not manufactured in the same facility. The recalled lots of medication were distributed between January and April 2019, but so far, Novartis has not received any reports of adverse events related to the recall.
Oral suspension of eltrombopag is indicated for certain patients with chronic immune thrombocytopenia, hepatitis C–associated thrombocytopenia, and severe aplastic anemia.
More information on the recalled lots and instructions on how to return the product can be found in the full announcement, which is also available through the Food and Drug Administration website.
Novartis has recalled three lots of 12.5-mg eltrombopag (Promacta) for oral suspension following discovery of possible contamination with peanut flour at a third-party manufacturing site.
Tablets at doses of 12.5 mg, 25 mg, 50 mg, and 75 mg are unaffected by this recall because they are not manufactured in the same facility. The recalled lots of medication were distributed between January and April 2019, but so far, Novartis has not received any reports of adverse events related to the recall.
Oral suspension of eltrombopag is indicated for certain patients with chronic immune thrombocytopenia, hepatitis C–associated thrombocytopenia, and severe aplastic anemia.
More information on the recalled lots and instructions on how to return the product can be found in the full announcement, which is also available through the Food and Drug Administration website.
FDA issues final guidance on seeking licensure for interchangeable biologics
The action provides “clarity for developers who want to demonstrate that their proposed biological product meets the statutory interchangeability standard under the Public Health Service Act,” Norman E. Sharpless, MD, the acting commissioner of the agency, said in a press release.
Biologics deemed “interchangeable” will be able to be substituted without the involvement of the prescriber, similar to how generic drugs are now routinely substituted for brand name drugs. On March 23, 2020, the FDA will be able to license such interchangeable products.
On May 13, the agency will consider what factors need to be weighed when determining whether an insulin product is biosimilar to or interchangeable with a reference product at a public hearing: “The Future of Insulin Biosimilars: Increasing Access and Facilitating the Efficient Development of Biosimilar and Interchangeable Insulin Products.”
“We also expect to hear stakeholder feedback on whether certain insulin products – for example, those that use insulin pumps for continuous subcutaneous infusion among the approved uses – raise unique scientific considerations that we should be considering when evaluating biosimilar or interchangeable insulin products. And importantly, we’ll also be seeking input directly from patients about their experience with insulin products, and this input will inform the FDA’s approach to implementing the regulatory pathway for biosimilar and interchangeable insulin products,” Dr. Sharpless said in the statement.
The ability to substitute an interchangeable insulin product – or any chronically used biologic medication – at the pharmacy could potentially increase access and lower costs for patients.
Dr. Sharpless added that the FDA has developed and is working to implement a Biosimilars Action Plan that includes a suite of ongoing efforts to encourage innovation and competition among biologics and the development of biosimilars.
The final guidance gives an overview of important scientific considerations in demonstrating interchangeability with a reference product and explains the scientific recommendations for an application or a supplement for a proposed interchangeable product. The guidance also explains potential ways to address the Biologics Price Competition and Innovation Act requirement for interchangeability that, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the reference product without alternating or switching.
“Our rigorous scientific standards for approval will be maintained for interchangeable biologics and should serve as assurance to health care professionals and patients that they can be confident in the safety and effectiveness of both interchangeable products and biosimilar products, just as they would be for reference products,” Dr. Sharpless said in the statement.
Medical specialty organizations have begun to weigh in on the FDA final guidance, “Considerations in Demonstrating Interchangeability with a Reference Product.”
The American College of Rheumatology applauded the FDA action.
“Specifically, we are pleased to see that the final guidance expects manufacturers to use robust switching studies. At least three switches with each switch crossing over to the alternate product will be needed to determine whether alternating between a biosimilar and its reference product impacts the safety or efficacy of the drug. The ACR believes these studies will provide an understanding of what patients are likely to experience when changing formularies in a multipayer, multistate market,” Dr. Angus Worthing, chair of the American College of Rheumatology’s Government Affairs Committee, said in a statement.
“We are also pleased to see the FDA finalize its approach to safety, immunogenicity, and efficacy for the demonstration of interchangeability. And we agree with the FDA that postmarketing safety monitoring for an interchangeable product should also have robust pharmacovigilance mechanisms in place. In order to improve clarity, the ACR suggests that FDA prescribing information for all biosimilars include statements about whether each agent is or is not interchangeable to the reference product,” he said. “The ACR shares the FDA’s goal of ensuring that more affordable treatments reach patients as quickly as possible and appreciates the agency’s measured and thoughtful approach throughout this process.”
The action provides “clarity for developers who want to demonstrate that their proposed biological product meets the statutory interchangeability standard under the Public Health Service Act,” Norman E. Sharpless, MD, the acting commissioner of the agency, said in a press release.
Biologics deemed “interchangeable” will be able to be substituted without the involvement of the prescriber, similar to how generic drugs are now routinely substituted for brand name drugs. On March 23, 2020, the FDA will be able to license such interchangeable products.
On May 13, the agency will consider what factors need to be weighed when determining whether an insulin product is biosimilar to or interchangeable with a reference product at a public hearing: “The Future of Insulin Biosimilars: Increasing Access and Facilitating the Efficient Development of Biosimilar and Interchangeable Insulin Products.”
“We also expect to hear stakeholder feedback on whether certain insulin products – for example, those that use insulin pumps for continuous subcutaneous infusion among the approved uses – raise unique scientific considerations that we should be considering when evaluating biosimilar or interchangeable insulin products. And importantly, we’ll also be seeking input directly from patients about their experience with insulin products, and this input will inform the FDA’s approach to implementing the regulatory pathway for biosimilar and interchangeable insulin products,” Dr. Sharpless said in the statement.
The ability to substitute an interchangeable insulin product – or any chronically used biologic medication – at the pharmacy could potentially increase access and lower costs for patients.
Dr. Sharpless added that the FDA has developed and is working to implement a Biosimilars Action Plan that includes a suite of ongoing efforts to encourage innovation and competition among biologics and the development of biosimilars.
The final guidance gives an overview of important scientific considerations in demonstrating interchangeability with a reference product and explains the scientific recommendations for an application or a supplement for a proposed interchangeable product. The guidance also explains potential ways to address the Biologics Price Competition and Innovation Act requirement for interchangeability that, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the reference product without alternating or switching.
“Our rigorous scientific standards for approval will be maintained for interchangeable biologics and should serve as assurance to health care professionals and patients that they can be confident in the safety and effectiveness of both interchangeable products and biosimilar products, just as they would be for reference products,” Dr. Sharpless said in the statement.
Medical specialty organizations have begun to weigh in on the FDA final guidance, “Considerations in Demonstrating Interchangeability with a Reference Product.”
The American College of Rheumatology applauded the FDA action.
“Specifically, we are pleased to see that the final guidance expects manufacturers to use robust switching studies. At least three switches with each switch crossing over to the alternate product will be needed to determine whether alternating between a biosimilar and its reference product impacts the safety or efficacy of the drug. The ACR believes these studies will provide an understanding of what patients are likely to experience when changing formularies in a multipayer, multistate market,” Dr. Angus Worthing, chair of the American College of Rheumatology’s Government Affairs Committee, said in a statement.
“We are also pleased to see the FDA finalize its approach to safety, immunogenicity, and efficacy for the demonstration of interchangeability. And we agree with the FDA that postmarketing safety monitoring for an interchangeable product should also have robust pharmacovigilance mechanisms in place. In order to improve clarity, the ACR suggests that FDA prescribing information for all biosimilars include statements about whether each agent is or is not interchangeable to the reference product,” he said. “The ACR shares the FDA’s goal of ensuring that more affordable treatments reach patients as quickly as possible and appreciates the agency’s measured and thoughtful approach throughout this process.”
The action provides “clarity for developers who want to demonstrate that their proposed biological product meets the statutory interchangeability standard under the Public Health Service Act,” Norman E. Sharpless, MD, the acting commissioner of the agency, said in a press release.
Biologics deemed “interchangeable” will be able to be substituted without the involvement of the prescriber, similar to how generic drugs are now routinely substituted for brand name drugs. On March 23, 2020, the FDA will be able to license such interchangeable products.
On May 13, the agency will consider what factors need to be weighed when determining whether an insulin product is biosimilar to or interchangeable with a reference product at a public hearing: “The Future of Insulin Biosimilars: Increasing Access and Facilitating the Efficient Development of Biosimilar and Interchangeable Insulin Products.”
“We also expect to hear stakeholder feedback on whether certain insulin products – for example, those that use insulin pumps for continuous subcutaneous infusion among the approved uses – raise unique scientific considerations that we should be considering when evaluating biosimilar or interchangeable insulin products. And importantly, we’ll also be seeking input directly from patients about their experience with insulin products, and this input will inform the FDA’s approach to implementing the regulatory pathway for biosimilar and interchangeable insulin products,” Dr. Sharpless said in the statement.
The ability to substitute an interchangeable insulin product – or any chronically used biologic medication – at the pharmacy could potentially increase access and lower costs for patients.
Dr. Sharpless added that the FDA has developed and is working to implement a Biosimilars Action Plan that includes a suite of ongoing efforts to encourage innovation and competition among biologics and the development of biosimilars.
The final guidance gives an overview of important scientific considerations in demonstrating interchangeability with a reference product and explains the scientific recommendations for an application or a supplement for a proposed interchangeable product. The guidance also explains potential ways to address the Biologics Price Competition and Innovation Act requirement for interchangeability that, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product will not be greater than the risk of using the reference product without alternating or switching.
“Our rigorous scientific standards for approval will be maintained for interchangeable biologics and should serve as assurance to health care professionals and patients that they can be confident in the safety and effectiveness of both interchangeable products and biosimilar products, just as they would be for reference products,” Dr. Sharpless said in the statement.
Medical specialty organizations have begun to weigh in on the FDA final guidance, “Considerations in Demonstrating Interchangeability with a Reference Product.”
The American College of Rheumatology applauded the FDA action.
“Specifically, we are pleased to see that the final guidance expects manufacturers to use robust switching studies. At least three switches with each switch crossing over to the alternate product will be needed to determine whether alternating between a biosimilar and its reference product impacts the safety or efficacy of the drug. The ACR believes these studies will provide an understanding of what patients are likely to experience when changing formularies in a multipayer, multistate market,” Dr. Angus Worthing, chair of the American College of Rheumatology’s Government Affairs Committee, said in a statement.
“We are also pleased to see the FDA finalize its approach to safety, immunogenicity, and efficacy for the demonstration of interchangeability. And we agree with the FDA that postmarketing safety monitoring for an interchangeable product should also have robust pharmacovigilance mechanisms in place. In order to improve clarity, the ACR suggests that FDA prescribing information for all biosimilars include statements about whether each agent is or is not interchangeable to the reference product,” he said. “The ACR shares the FDA’s goal of ensuring that more affordable treatments reach patients as quickly as possible and appreciates the agency’s measured and thoughtful approach throughout this process.”
In a tight vote, FDA panel backs mannitol for CF
A Food and Drug Administration Advisory Committee voted that the benefit-risk profile of an inhaled treatment for cystic fibrosis merits approval of the drug – dry powder mannitol (DPM).
Mannitol is a naturally occurring sugar alcohol that is used as a low-calorie sweetener; it is generally recognized as safe when taken enterically. Inhaled DPM, marketed as Aridol, is currently approved as a bronchoprovocation agent. For the current indication, DPM is given as 10x40-mg capsules twice daily.
In a 9-7 vote, the FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) decided that DPM’s modest potential to improve pulmonary function in adults with cystic fibrosis (CF) outweighed a potential signal for increased exacerbations seen in clinical trials.
Chiesi USA Inc. is seeking approval of DPM for the management of cystic fibrosis to improve pulmonary function in patients 18 years of age and older in conjunction with standard therapies. It plans to market DPM as Bronchitol.
Some committee members who voted against approval, including PADAC chair David H. Au, MD, worried that DPM’s ease of use might prompt patients and caregivers to substitute it for inhaled hypertonic saline, a medication that’s more burdensome to use but has a longer track record for efficacy and safety. While hypertonic saline requires cumbersome equipment and cleaning regimens and takes 20-30 minutes to administer, DPM is administered over about 5 minutes via a series of capsules inserted into a small inhaler device.
“I was very impressed by conversations that we heard from the community that this will be viewed as a substitute drug [for hypertonic saline],” said Dr. Au, professor of medicine at the University of Washington, Seattle. “Before we make that leap of faith ... we have to better understand how it has to be used.” He also acknowledged that making the call for DPM was “challenging.”
Other committee members were reassured by the fact that DPM is approved for adult use in 35 countries; it’s been in use since 2011 in Australia for adults and children.
Some members also noted an unmet need in CF therapies and placed confidence in those treating CF patients to find ways to use DPM safely and effectively. “I’m really counting on the cystic fibrosis clinicians who do this for a living to figure out where to use this in their armamentarium,” said John M. Kelso, MD, an allergist at Scripps Clinic, San Diego.
In 2012, the initial new drug application submitted by Pharmaxis, which then held marketing rights to DPM, resulted in a “no” vote for approval from PADAC, and eventual FDA denial of approval. The initial submission was supported by two phase 3 clinical trials, 301 and 302, that included pediatric patients. In the pediatric population, there was concern for increased hemoptysis with DPM, so the FDA advised the drug’s marketers to consider seeking approval for an adult population only in its reapplication. The current submission followed a new double-blind, randomized, placebo-controlled trial, study 303, that included adults with CF aged 18 or over.
All three studies had similar designs, tracking change from baseline in forced expiratory volume in one second (FEV1) from baseline to the end of the 26-week study period. In addition to this primary endpoint, secondary endpoints included other pulmonary function measures, as well as the number of protocol-defined pulmonary exacerbations (PDPEs). Participants also reported quality of life and symptom measures on the Cystic Fibrosis Questionnaire–Revised (CFQ-R).
In study 301, the dropout rate approached one in three participants with higher discontinuation in the intervention than the control arm, causing significant statistical problems in dealing with missing data. Thus, said the FDA’s Robert Lim, MD, though this study had positive results for FEV1, it was not “statistically robust.”
The second study, 302, did not meet its primary endpoint, and there was “no support from secondary endpoints” for efficacy, said Dr. Lim, a clinical team leader in the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products.
The current submission was also supported by a new post hoc subgroup analysis of adults in studies 301 and 302. A total of 414 patients receiving DPM and 347 receiving placebo (DPM at a nontherapeutic level) were included in the integrated analysis of patients from all three studies. Studies 301 and 302 both had open-label extension arms, allowing more patients to be included in safety data.
The problems caused by the missing data from study 301 were addressed in the design of study 303 by encouraging patients who discontinued the study drug to continue data collection efforts for the study. Dropout rates were lower overall in study 303 and balanced between arms.
Over the 26-week duration of study 303, investigators saw a statistically significant improvement in FEV1 of about 50 mL, according to the FDA’s analysis. Post hoc analyses of studies 301 and 302 showed point estimate increases of approximately 80 mL, according to Dr. Lim.
In its presentations, Chiesi USA presented its integrated analysis of adult data from the three clinical trials. The analysis showed an increase in FEV1 from baseline of 73 mL for the DPM group, compared with an increase of 7 mL for the control group, using an intention-to-treat population (P less than .001). The committee heard evidence that in adults with CF, pulmonary function typically decreases by 1%-3% annually.
The PDPE rate was slightly higher in the DPM group than in the control group in studies 302 and 303, but the differences were not statistically significant. These findings have a backdrop of an overall low rate of PDPEs ranging from 0.221 to 0.995 per year, according to Chiesi presenter Scott Donaldson, MD, a pulmonologist who directs the adult cystic fibrosis center at the University of North Carolina at Chapel Hill.
When looking at the subgroup of United States study participants, the DPM integrated cohort included more patients with a history of prior pulmonary exacerbations. In the DPM group, 45% of U.S. participants had at least one exacerbation in the prior year, and 20% had two or more exacerbations, compared with 38% and 14%, respectively, in the control group. Chiesi argued that this imbalance was likely responsible for the increased exacerbation rate.
The sponsor and the FDA used different imputation methods to account for missing data from the earlier studies, complicating interpretation of the potential signal for increased exacerbations.
Quality of life data were similar between groups across the studies.
In the end, the view of the “yes” voters was encapsulated by James M. Tracy, DO, an allergist in private practice in Omaha, Neb. “This is not a drug for everybody; but absolutely, it’s a drug for somebody. Ultimately we have to make that decision – I do think that we study populations, but we really take care of people.”
The FDA usually follows the recommendations of its advisory panels.
A Food and Drug Administration Advisory Committee voted that the benefit-risk profile of an inhaled treatment for cystic fibrosis merits approval of the drug – dry powder mannitol (DPM).
Mannitol is a naturally occurring sugar alcohol that is used as a low-calorie sweetener; it is generally recognized as safe when taken enterically. Inhaled DPM, marketed as Aridol, is currently approved as a bronchoprovocation agent. For the current indication, DPM is given as 10x40-mg capsules twice daily.
In a 9-7 vote, the FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) decided that DPM’s modest potential to improve pulmonary function in adults with cystic fibrosis (CF) outweighed a potential signal for increased exacerbations seen in clinical trials.
Chiesi USA Inc. is seeking approval of DPM for the management of cystic fibrosis to improve pulmonary function in patients 18 years of age and older in conjunction with standard therapies. It plans to market DPM as Bronchitol.
Some committee members who voted against approval, including PADAC chair David H. Au, MD, worried that DPM’s ease of use might prompt patients and caregivers to substitute it for inhaled hypertonic saline, a medication that’s more burdensome to use but has a longer track record for efficacy and safety. While hypertonic saline requires cumbersome equipment and cleaning regimens and takes 20-30 minutes to administer, DPM is administered over about 5 minutes via a series of capsules inserted into a small inhaler device.
“I was very impressed by conversations that we heard from the community that this will be viewed as a substitute drug [for hypertonic saline],” said Dr. Au, professor of medicine at the University of Washington, Seattle. “Before we make that leap of faith ... we have to better understand how it has to be used.” He also acknowledged that making the call for DPM was “challenging.”
Other committee members were reassured by the fact that DPM is approved for adult use in 35 countries; it’s been in use since 2011 in Australia for adults and children.
Some members also noted an unmet need in CF therapies and placed confidence in those treating CF patients to find ways to use DPM safely and effectively. “I’m really counting on the cystic fibrosis clinicians who do this for a living to figure out where to use this in their armamentarium,” said John M. Kelso, MD, an allergist at Scripps Clinic, San Diego.
In 2012, the initial new drug application submitted by Pharmaxis, which then held marketing rights to DPM, resulted in a “no” vote for approval from PADAC, and eventual FDA denial of approval. The initial submission was supported by two phase 3 clinical trials, 301 and 302, that included pediatric patients. In the pediatric population, there was concern for increased hemoptysis with DPM, so the FDA advised the drug’s marketers to consider seeking approval for an adult population only in its reapplication. The current submission followed a new double-blind, randomized, placebo-controlled trial, study 303, that included adults with CF aged 18 or over.
All three studies had similar designs, tracking change from baseline in forced expiratory volume in one second (FEV1) from baseline to the end of the 26-week study period. In addition to this primary endpoint, secondary endpoints included other pulmonary function measures, as well as the number of protocol-defined pulmonary exacerbations (PDPEs). Participants also reported quality of life and symptom measures on the Cystic Fibrosis Questionnaire–Revised (CFQ-R).
In study 301, the dropout rate approached one in three participants with higher discontinuation in the intervention than the control arm, causing significant statistical problems in dealing with missing data. Thus, said the FDA’s Robert Lim, MD, though this study had positive results for FEV1, it was not “statistically robust.”
The second study, 302, did not meet its primary endpoint, and there was “no support from secondary endpoints” for efficacy, said Dr. Lim, a clinical team leader in the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products.
The current submission was also supported by a new post hoc subgroup analysis of adults in studies 301 and 302. A total of 414 patients receiving DPM and 347 receiving placebo (DPM at a nontherapeutic level) were included in the integrated analysis of patients from all three studies. Studies 301 and 302 both had open-label extension arms, allowing more patients to be included in safety data.
The problems caused by the missing data from study 301 were addressed in the design of study 303 by encouraging patients who discontinued the study drug to continue data collection efforts for the study. Dropout rates were lower overall in study 303 and balanced between arms.
Over the 26-week duration of study 303, investigators saw a statistically significant improvement in FEV1 of about 50 mL, according to the FDA’s analysis. Post hoc analyses of studies 301 and 302 showed point estimate increases of approximately 80 mL, according to Dr. Lim.
In its presentations, Chiesi USA presented its integrated analysis of adult data from the three clinical trials. The analysis showed an increase in FEV1 from baseline of 73 mL for the DPM group, compared with an increase of 7 mL for the control group, using an intention-to-treat population (P less than .001). The committee heard evidence that in adults with CF, pulmonary function typically decreases by 1%-3% annually.
The PDPE rate was slightly higher in the DPM group than in the control group in studies 302 and 303, but the differences were not statistically significant. These findings have a backdrop of an overall low rate of PDPEs ranging from 0.221 to 0.995 per year, according to Chiesi presenter Scott Donaldson, MD, a pulmonologist who directs the adult cystic fibrosis center at the University of North Carolina at Chapel Hill.
When looking at the subgroup of United States study participants, the DPM integrated cohort included more patients with a history of prior pulmonary exacerbations. In the DPM group, 45% of U.S. participants had at least one exacerbation in the prior year, and 20% had two or more exacerbations, compared with 38% and 14%, respectively, in the control group. Chiesi argued that this imbalance was likely responsible for the increased exacerbation rate.
The sponsor and the FDA used different imputation methods to account for missing data from the earlier studies, complicating interpretation of the potential signal for increased exacerbations.
Quality of life data were similar between groups across the studies.
In the end, the view of the “yes” voters was encapsulated by James M. Tracy, DO, an allergist in private practice in Omaha, Neb. “This is not a drug for everybody; but absolutely, it’s a drug for somebody. Ultimately we have to make that decision – I do think that we study populations, but we really take care of people.”
The FDA usually follows the recommendations of its advisory panels.
A Food and Drug Administration Advisory Committee voted that the benefit-risk profile of an inhaled treatment for cystic fibrosis merits approval of the drug – dry powder mannitol (DPM).
Mannitol is a naturally occurring sugar alcohol that is used as a low-calorie sweetener; it is generally recognized as safe when taken enterically. Inhaled DPM, marketed as Aridol, is currently approved as a bronchoprovocation agent. For the current indication, DPM is given as 10x40-mg capsules twice daily.
In a 9-7 vote, the FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) decided that DPM’s modest potential to improve pulmonary function in adults with cystic fibrosis (CF) outweighed a potential signal for increased exacerbations seen in clinical trials.
Chiesi USA Inc. is seeking approval of DPM for the management of cystic fibrosis to improve pulmonary function in patients 18 years of age and older in conjunction with standard therapies. It plans to market DPM as Bronchitol.
Some committee members who voted against approval, including PADAC chair David H. Au, MD, worried that DPM’s ease of use might prompt patients and caregivers to substitute it for inhaled hypertonic saline, a medication that’s more burdensome to use but has a longer track record for efficacy and safety. While hypertonic saline requires cumbersome equipment and cleaning regimens and takes 20-30 minutes to administer, DPM is administered over about 5 minutes via a series of capsules inserted into a small inhaler device.
“I was very impressed by conversations that we heard from the community that this will be viewed as a substitute drug [for hypertonic saline],” said Dr. Au, professor of medicine at the University of Washington, Seattle. “Before we make that leap of faith ... we have to better understand how it has to be used.” He also acknowledged that making the call for DPM was “challenging.”
Other committee members were reassured by the fact that DPM is approved for adult use in 35 countries; it’s been in use since 2011 in Australia for adults and children.
Some members also noted an unmet need in CF therapies and placed confidence in those treating CF patients to find ways to use DPM safely and effectively. “I’m really counting on the cystic fibrosis clinicians who do this for a living to figure out where to use this in their armamentarium,” said John M. Kelso, MD, an allergist at Scripps Clinic, San Diego.
In 2012, the initial new drug application submitted by Pharmaxis, which then held marketing rights to DPM, resulted in a “no” vote for approval from PADAC, and eventual FDA denial of approval. The initial submission was supported by two phase 3 clinical trials, 301 and 302, that included pediatric patients. In the pediatric population, there was concern for increased hemoptysis with DPM, so the FDA advised the drug’s marketers to consider seeking approval for an adult population only in its reapplication. The current submission followed a new double-blind, randomized, placebo-controlled trial, study 303, that included adults with CF aged 18 or over.
All three studies had similar designs, tracking change from baseline in forced expiratory volume in one second (FEV1) from baseline to the end of the 26-week study period. In addition to this primary endpoint, secondary endpoints included other pulmonary function measures, as well as the number of protocol-defined pulmonary exacerbations (PDPEs). Participants also reported quality of life and symptom measures on the Cystic Fibrosis Questionnaire–Revised (CFQ-R).
In study 301, the dropout rate approached one in three participants with higher discontinuation in the intervention than the control arm, causing significant statistical problems in dealing with missing data. Thus, said the FDA’s Robert Lim, MD, though this study had positive results for FEV1, it was not “statistically robust.”
The second study, 302, did not meet its primary endpoint, and there was “no support from secondary endpoints” for efficacy, said Dr. Lim, a clinical team leader in the FDA’s Division of Pulmonary, Allergy, and Rheumatology Products.
The current submission was also supported by a new post hoc subgroup analysis of adults in studies 301 and 302. A total of 414 patients receiving DPM and 347 receiving placebo (DPM at a nontherapeutic level) were included in the integrated analysis of patients from all three studies. Studies 301 and 302 both had open-label extension arms, allowing more patients to be included in safety data.
The problems caused by the missing data from study 301 were addressed in the design of study 303 by encouraging patients who discontinued the study drug to continue data collection efforts for the study. Dropout rates were lower overall in study 303 and balanced between arms.
Over the 26-week duration of study 303, investigators saw a statistically significant improvement in FEV1 of about 50 mL, according to the FDA’s analysis. Post hoc analyses of studies 301 and 302 showed point estimate increases of approximately 80 mL, according to Dr. Lim.
In its presentations, Chiesi USA presented its integrated analysis of adult data from the three clinical trials. The analysis showed an increase in FEV1 from baseline of 73 mL for the DPM group, compared with an increase of 7 mL for the control group, using an intention-to-treat population (P less than .001). The committee heard evidence that in adults with CF, pulmonary function typically decreases by 1%-3% annually.
The PDPE rate was slightly higher in the DPM group than in the control group in studies 302 and 303, but the differences were not statistically significant. These findings have a backdrop of an overall low rate of PDPEs ranging from 0.221 to 0.995 per year, according to Chiesi presenter Scott Donaldson, MD, a pulmonologist who directs the adult cystic fibrosis center at the University of North Carolina at Chapel Hill.
When looking at the subgroup of United States study participants, the DPM integrated cohort included more patients with a history of prior pulmonary exacerbations. In the DPM group, 45% of U.S. participants had at least one exacerbation in the prior year, and 20% had two or more exacerbations, compared with 38% and 14%, respectively, in the control group. Chiesi argued that this imbalance was likely responsible for the increased exacerbation rate.
The sponsor and the FDA used different imputation methods to account for missing data from the earlier studies, complicating interpretation of the potential signal for increased exacerbations.
Quality of life data were similar between groups across the studies.
In the end, the view of the “yes” voters was encapsulated by James M. Tracy, DO, an allergist in private practice in Omaha, Neb. “This is not a drug for everybody; but absolutely, it’s a drug for somebody. Ultimately we have to make that decision – I do think that we study populations, but we really take care of people.”
The FDA usually follows the recommendations of its advisory panels.
FROM AN FDA ADVISORY COMMITTEE HEARING
Insomnia meds get boxed warning from FDA
The Food and Drug Administration will now require that certain
Complex sleep behaviors have been seen with these medications in patients with and without a history of them, at low doses, and even after one dose of the medication. They’ve also been observed with and without concomitant use of alcohol or other CNS depressants.
Health care professionals should advise patients about these risks, even though they are rare. Patients should contact health care professionals if they either experience a complex sleep behavior while not fully awake on one of these medicines or have performed activities they don’t remember while taking the medicine.
More information about these risks and the safety warnings can be found in the FDA’s safety announcement. Other information is also available in a press announcement from the agency.
The Food and Drug Administration will now require that certain
Complex sleep behaviors have been seen with these medications in patients with and without a history of them, at low doses, and even after one dose of the medication. They’ve also been observed with and without concomitant use of alcohol or other CNS depressants.
Health care professionals should advise patients about these risks, even though they are rare. Patients should contact health care professionals if they either experience a complex sleep behavior while not fully awake on one of these medicines or have performed activities they don’t remember while taking the medicine.
More information about these risks and the safety warnings can be found in the FDA’s safety announcement. Other information is also available in a press announcement from the agency.
The Food and Drug Administration will now require that certain
Complex sleep behaviors have been seen with these medications in patients with and without a history of them, at low doses, and even after one dose of the medication. They’ve also been observed with and without concomitant use of alcohol or other CNS depressants.
Health care professionals should advise patients about these risks, even though they are rare. Patients should contact health care professionals if they either experience a complex sleep behavior while not fully awake on one of these medicines or have performed activities they don’t remember while taking the medicine.
More information about these risks and the safety warnings can be found in the FDA’s safety announcement. Other information is also available in a press announcement from the agency.
Ruzurgi approved for Lambert-Eaton myasthenic syndrome in patients under age 17
Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.
The approval is the first for a LEMS treatment specifically for pediatric patients.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.
Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.
A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.
The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.
The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.
Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.
The approval is the first for a LEMS treatment specifically for pediatric patients.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.
Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.
A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.
The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.
The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.
Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.
The approval is the first for a LEMS treatment specifically for pediatric patients.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.
Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.
A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.
The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.
The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.
FDA approves Qternmet XR as adjunct therapy for glycemic improvement in type 2 diabetes
The Food and Drug Administration has approved Qternmet XR (dapagliflozin/saxagliptin/metformin) as an oral adjunct therapy to diet and exercise for the improvement of glycemic control in patients with type 2 diabetes, according to AstraZeneca.
FDA approval is based on results from a pair of phase 3 trials that tested different combinations of dapagliflozin and saxagliptin in patients with inadequately controlled type 2 diabetes who were also receiving metformin over a 24-week period. In both trials, treatment with dapagliflozin/saxagliptin/metformin decreased hemoglobin A1c by statistically significant amounts, and increased the number of patients with HbA1c levels below 7%
The safety results of Qternmet XR was consistent with each component medication’s known profile.
The Food and Drug Administration has approved Qternmet XR (dapagliflozin/saxagliptin/metformin) as an oral adjunct therapy to diet and exercise for the improvement of glycemic control in patients with type 2 diabetes, according to AstraZeneca.
FDA approval is based on results from a pair of phase 3 trials that tested different combinations of dapagliflozin and saxagliptin in patients with inadequately controlled type 2 diabetes who were also receiving metformin over a 24-week period. In both trials, treatment with dapagliflozin/saxagliptin/metformin decreased hemoglobin A1c by statistically significant amounts, and increased the number of patients with HbA1c levels below 7%
The safety results of Qternmet XR was consistent with each component medication’s known profile.
The Food and Drug Administration has approved Qternmet XR (dapagliflozin/saxagliptin/metformin) as an oral adjunct therapy to diet and exercise for the improvement of glycemic control in patients with type 2 diabetes, according to AstraZeneca.
FDA approval is based on results from a pair of phase 3 trials that tested different combinations of dapagliflozin and saxagliptin in patients with inadequately controlled type 2 diabetes who were also receiving metformin over a 24-week period. In both trials, treatment with dapagliflozin/saxagliptin/metformin decreased hemoglobin A1c by statistically significant amounts, and increased the number of patients with HbA1c levels below 7%
The safety results of Qternmet XR was consistent with each component medication’s known profile.
FDA approves Vyndaqel, Vyndamax for amyloidosis-based heart disease
The disease is caused by the buildup of abnormal deposits of amyloid in the body’s organs and tissues, interfering with normal function, and most often occurs in the heart and nervous system. Symptoms associated with amyloid buildup in the heart include shortness of breath, fatigue, heart failure, loss of consciousness, abnormal heart rhythms, and death.
FDA approval of both drugs was based on results of a clinical trial in which 441 patients with transthyretin-mediated amyloidosis received either tafamidis meglumine or placebo. After a mean of 30 months, patients who received tafamidis meglumine had a higher survival rate and a lower number of cardiovascular-related hospitalizations than did patients in the placebo group.
No drug-associated side effects have yet been identified; however, tafamidis can cause fetal harm when administered to a pregnant woman.
“Transthyretin-mediated amyloidosis is a rare, debilitating, and often fatal disease. The treatments we’re approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis,” said Norman Stockbridge, MD, PhD, director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research.
Find the full press release on the FDA website.
The disease is caused by the buildup of abnormal deposits of amyloid in the body’s organs and tissues, interfering with normal function, and most often occurs in the heart and nervous system. Symptoms associated with amyloid buildup in the heart include shortness of breath, fatigue, heart failure, loss of consciousness, abnormal heart rhythms, and death.
FDA approval of both drugs was based on results of a clinical trial in which 441 patients with transthyretin-mediated amyloidosis received either tafamidis meglumine or placebo. After a mean of 30 months, patients who received tafamidis meglumine had a higher survival rate and a lower number of cardiovascular-related hospitalizations than did patients in the placebo group.
No drug-associated side effects have yet been identified; however, tafamidis can cause fetal harm when administered to a pregnant woman.
“Transthyretin-mediated amyloidosis is a rare, debilitating, and often fatal disease. The treatments we’re approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis,” said Norman Stockbridge, MD, PhD, director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research.
Find the full press release on the FDA website.
The disease is caused by the buildup of abnormal deposits of amyloid in the body’s organs and tissues, interfering with normal function, and most often occurs in the heart and nervous system. Symptoms associated with amyloid buildup in the heart include shortness of breath, fatigue, heart failure, loss of consciousness, abnormal heart rhythms, and death.
FDA approval of both drugs was based on results of a clinical trial in which 441 patients with transthyretin-mediated amyloidosis received either tafamidis meglumine or placebo. After a mean of 30 months, patients who received tafamidis meglumine had a higher survival rate and a lower number of cardiovascular-related hospitalizations than did patients in the placebo group.
No drug-associated side effects have yet been identified; however, tafamidis can cause fetal harm when administered to a pregnant woman.
“Transthyretin-mediated amyloidosis is a rare, debilitating, and often fatal disease. The treatments we’re approving today are an important advancement in the treatment of the cardiomyopathy caused by transthyretin-mediated amyloidosis,” said Norman Stockbridge, MD, PhD, director of the Division of Cardiovascular and Renal Drugs in the FDA’s Center for Drug Evaluation and Research.
Find the full press release on the FDA website.
FDA approves T-DM1 as adjuvant treatment
The Food and Drug Administration has approved the antibody-drug conjugate trastuzumab emtansine (T-DM1) for adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab (Herceptin).
Approval of adjuvant T-DM1, marketed as Kadcyla, was based on a reduced risk of breast cancer recurrence or death in the phase 3 KATHERINE trial. In KATHERINE, over 1,400 patients with HER2-positive early breast cancer who had residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment were randomized to adjuvant therapy with T-DM1 or trastuzumab. The 3-year invasive disease-free survival rate was 88.3% for those taking T-DM1, compared with 77.0% for patients assigned to adjuvant trastuzumab (hazard ratio, 0.50; 95% confidence interval, 0.39-0.64; P less than .0001). Results of KATHERINE were presented at the 2018 San Antonio Breast Cancer Symposium and simultaneously published in the New England Journal of Medicine.
The most common grade 3 or greater adverse events for those in the T-DM1 arm included decreased platelet count in 5.7% and hypertension in 2.0%. The most common side effects with T-DM1 were fatigue, nausea, increased blood levels of liver enzymes, musculoskeletal pain, bleeding, decreased platelet count, headache, numbness in the hands or feet, and joint pain.
T-DM1 was previously approved to treat metastatic HER2-positive breast cancer after prior treatment with trastuzumab and a taxane.
“This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot program, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech (Roche), the developer of T-DM1, in a press release announcing the current approval.
The Food and Drug Administration has approved the antibody-drug conjugate trastuzumab emtansine (T-DM1) for adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab (Herceptin).
Approval of adjuvant T-DM1, marketed as Kadcyla, was based on a reduced risk of breast cancer recurrence or death in the phase 3 KATHERINE trial. In KATHERINE, over 1,400 patients with HER2-positive early breast cancer who had residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment were randomized to adjuvant therapy with T-DM1 or trastuzumab. The 3-year invasive disease-free survival rate was 88.3% for those taking T-DM1, compared with 77.0% for patients assigned to adjuvant trastuzumab (hazard ratio, 0.50; 95% confidence interval, 0.39-0.64; P less than .0001). Results of KATHERINE were presented at the 2018 San Antonio Breast Cancer Symposium and simultaneously published in the New England Journal of Medicine.
The most common grade 3 or greater adverse events for those in the T-DM1 arm included decreased platelet count in 5.7% and hypertension in 2.0%. The most common side effects with T-DM1 were fatigue, nausea, increased blood levels of liver enzymes, musculoskeletal pain, bleeding, decreased platelet count, headache, numbness in the hands or feet, and joint pain.
T-DM1 was previously approved to treat metastatic HER2-positive breast cancer after prior treatment with trastuzumab and a taxane.
“This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot program, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech (Roche), the developer of T-DM1, in a press release announcing the current approval.
The Food and Drug Administration has approved the antibody-drug conjugate trastuzumab emtansine (T-DM1) for adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab (Herceptin).
Approval of adjuvant T-DM1, marketed as Kadcyla, was based on a reduced risk of breast cancer recurrence or death in the phase 3 KATHERINE trial. In KATHERINE, over 1,400 patients with HER2-positive early breast cancer who had residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment were randomized to adjuvant therapy with T-DM1 or trastuzumab. The 3-year invasive disease-free survival rate was 88.3% for those taking T-DM1, compared with 77.0% for patients assigned to adjuvant trastuzumab (hazard ratio, 0.50; 95% confidence interval, 0.39-0.64; P less than .0001). Results of KATHERINE were presented at the 2018 San Antonio Breast Cancer Symposium and simultaneously published in the New England Journal of Medicine.
The most common grade 3 or greater adverse events for those in the T-DM1 arm included decreased platelet count in 5.7% and hypertension in 2.0%. The most common side effects with T-DM1 were fatigue, nausea, increased blood levels of liver enzymes, musculoskeletal pain, bleeding, decreased platelet count, headache, numbness in the hands or feet, and joint pain.
T-DM1 was previously approved to treat metastatic HER2-positive breast cancer after prior treatment with trastuzumab and a taxane.
“This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot program, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech (Roche), the developer of T-DM1, in a press release announcing the current approval.
FDA opts not to ban textured breast implants
The Food and Drug Administration decided to continue to allow U.S. sales of textured breast implants, which have been identified as the cause of a rare but significant cancer, breast implant–associated anaplastic large cell lymphoma.
A statement the agency released on May 2 said “The FDA does not believe that, on the basis of available data and information, the device [textured implants] meets the banning standard set forth in the Federal Food and Drug Cosmetic Act.” roughly half of them in the United States.
In coming to this decision, following 2 days of public testimony and discussions by an advisory committee in late March, the FDA is bucking the path taken by regulatory bodies of the European Union as well as several other counties. The EU acted in December 2018 to produce the equivalent of a ban on sales of textured breast implants marketed by Allergan. Then in April 2019, the French drug and device regulatory agency expanded this ban to textured breast implants sold by five other companies.
During the FDA advisory committee meeting in March, one of the world’s experts on BIA-ALCL, Mark W. Clemens, MD, a plastic surgeon at MD Anderson Cancer Center in Houston, said that of about 500 case reports received by the FDA, not one had involved a confirmed and “pure” episode of BIA-ALCL linked with a smooth breast implant. A team of experts recently reached the same conclusion when reviewing the reported worldwide incidence of BIA-ALCL in a published review (Plast Reconstr Surg. 2019 March;143[3S]:30S-40S).
Despite these reports, the FDA said in its new statement that “While the majority of women who develop BIA-ALCL have had textured implants, there are known cases in women with smooth-surface breast implants, and many reports do not include the surface texture of the implant at the time of diagnosis.” The agency added that it is “focused on strengthening the evidence generated to help inform future regulatory action.” During the March advisory committee meeting, some members of the panel spoke against a marketing ban on textured implants for reasons such as the modest number of reported cases and because of the importance of having a textured implant option available.
The FDA took several other notable steps in its May 2 statement:
The agency formally acknowledged that many breast implant recipients have reported experiencing adverse effects that include chronic fatigue, cognitive issues, and joint and muscle pain. “While the FDA doesn’t have definitive evidence demonstrating breast implants cause these symptoms, the current evidence supports that some women experience systemic symptoms that may resolve when their breast implants are removed.” The agency also cited the term that patients have coined for these symptoms: Breast Implant Illness.
The FDA made a commitment to “take steps to improve the information available to women and health care professionals about the risks of breast implants,” including the risk for BIA-ALCL, the increased risk for this cancer with textured implants, and the risk for systemic symptoms. The agency said it would work with stakeholders on possible changes to breast implant labeling, including a possible boxed warning, and a patient-decision checklist.
The FDA announced a change in how manufacturers will file medical device reports for breast implants. The agency will no longer allow these filings to be “summary” reports and will instead require manufacturers to file full individual medical device reports for each case that will be publicly available, with the intent to make reporting more transparent and complete.
Finally, the FDA announced that it would partner with two U.S. breast implant registries, the PROFILE registry of BIA-ALCL cases, and the National Breast Implant Registry, both run by the Plastic Surgery Foundation.
The FDA did not address in its statement other issues that came up during the March advisory committee hearings, including a panel recommendation to change follow-up imaging from MRI to ultrasound for monitoring women with implants for rupture, and the extensive, off-label use of surgical mesh during breast implant surgery.
The Food and Drug Administration decided to continue to allow U.S. sales of textured breast implants, which have been identified as the cause of a rare but significant cancer, breast implant–associated anaplastic large cell lymphoma.
A statement the agency released on May 2 said “The FDA does not believe that, on the basis of available data and information, the device [textured implants] meets the banning standard set forth in the Federal Food and Drug Cosmetic Act.” roughly half of them in the United States.
In coming to this decision, following 2 days of public testimony and discussions by an advisory committee in late March, the FDA is bucking the path taken by regulatory bodies of the European Union as well as several other counties. The EU acted in December 2018 to produce the equivalent of a ban on sales of textured breast implants marketed by Allergan. Then in April 2019, the French drug and device regulatory agency expanded this ban to textured breast implants sold by five other companies.
During the FDA advisory committee meeting in March, one of the world’s experts on BIA-ALCL, Mark W. Clemens, MD, a plastic surgeon at MD Anderson Cancer Center in Houston, said that of about 500 case reports received by the FDA, not one had involved a confirmed and “pure” episode of BIA-ALCL linked with a smooth breast implant. A team of experts recently reached the same conclusion when reviewing the reported worldwide incidence of BIA-ALCL in a published review (Plast Reconstr Surg. 2019 March;143[3S]:30S-40S).
Despite these reports, the FDA said in its new statement that “While the majority of women who develop BIA-ALCL have had textured implants, there are known cases in women with smooth-surface breast implants, and many reports do not include the surface texture of the implant at the time of diagnosis.” The agency added that it is “focused on strengthening the evidence generated to help inform future regulatory action.” During the March advisory committee meeting, some members of the panel spoke against a marketing ban on textured implants for reasons such as the modest number of reported cases and because of the importance of having a textured implant option available.
The FDA took several other notable steps in its May 2 statement:
The agency formally acknowledged that many breast implant recipients have reported experiencing adverse effects that include chronic fatigue, cognitive issues, and joint and muscle pain. “While the FDA doesn’t have definitive evidence demonstrating breast implants cause these symptoms, the current evidence supports that some women experience systemic symptoms that may resolve when their breast implants are removed.” The agency also cited the term that patients have coined for these symptoms: Breast Implant Illness.
The FDA made a commitment to “take steps to improve the information available to women and health care professionals about the risks of breast implants,” including the risk for BIA-ALCL, the increased risk for this cancer with textured implants, and the risk for systemic symptoms. The agency said it would work with stakeholders on possible changes to breast implant labeling, including a possible boxed warning, and a patient-decision checklist.
The FDA announced a change in how manufacturers will file medical device reports for breast implants. The agency will no longer allow these filings to be “summary” reports and will instead require manufacturers to file full individual medical device reports for each case that will be publicly available, with the intent to make reporting more transparent and complete.
Finally, the FDA announced that it would partner with two U.S. breast implant registries, the PROFILE registry of BIA-ALCL cases, and the National Breast Implant Registry, both run by the Plastic Surgery Foundation.
The FDA did not address in its statement other issues that came up during the March advisory committee hearings, including a panel recommendation to change follow-up imaging from MRI to ultrasound for monitoring women with implants for rupture, and the extensive, off-label use of surgical mesh during breast implant surgery.
The Food and Drug Administration decided to continue to allow U.S. sales of textured breast implants, which have been identified as the cause of a rare but significant cancer, breast implant–associated anaplastic large cell lymphoma.
A statement the agency released on May 2 said “The FDA does not believe that, on the basis of available data and information, the device [textured implants] meets the banning standard set forth in the Federal Food and Drug Cosmetic Act.” roughly half of them in the United States.
In coming to this decision, following 2 days of public testimony and discussions by an advisory committee in late March, the FDA is bucking the path taken by regulatory bodies of the European Union as well as several other counties. The EU acted in December 2018 to produce the equivalent of a ban on sales of textured breast implants marketed by Allergan. Then in April 2019, the French drug and device regulatory agency expanded this ban to textured breast implants sold by five other companies.
During the FDA advisory committee meeting in March, one of the world’s experts on BIA-ALCL, Mark W. Clemens, MD, a plastic surgeon at MD Anderson Cancer Center in Houston, said that of about 500 case reports received by the FDA, not one had involved a confirmed and “pure” episode of BIA-ALCL linked with a smooth breast implant. A team of experts recently reached the same conclusion when reviewing the reported worldwide incidence of BIA-ALCL in a published review (Plast Reconstr Surg. 2019 March;143[3S]:30S-40S).
Despite these reports, the FDA said in its new statement that “While the majority of women who develop BIA-ALCL have had textured implants, there are known cases in women with smooth-surface breast implants, and many reports do not include the surface texture of the implant at the time of diagnosis.” The agency added that it is “focused on strengthening the evidence generated to help inform future regulatory action.” During the March advisory committee meeting, some members of the panel spoke against a marketing ban on textured implants for reasons such as the modest number of reported cases and because of the importance of having a textured implant option available.
The FDA took several other notable steps in its May 2 statement:
The agency formally acknowledged that many breast implant recipients have reported experiencing adverse effects that include chronic fatigue, cognitive issues, and joint and muscle pain. “While the FDA doesn’t have definitive evidence demonstrating breast implants cause these symptoms, the current evidence supports that some women experience systemic symptoms that may resolve when their breast implants are removed.” The agency also cited the term that patients have coined for these symptoms: Breast Implant Illness.
The FDA made a commitment to “take steps to improve the information available to women and health care professionals about the risks of breast implants,” including the risk for BIA-ALCL, the increased risk for this cancer with textured implants, and the risk for systemic symptoms. The agency said it would work with stakeholders on possible changes to breast implant labeling, including a possible boxed warning, and a patient-decision checklist.
The FDA announced a change in how manufacturers will file medical device reports for breast implants. The agency will no longer allow these filings to be “summary” reports and will instead require manufacturers to file full individual medical device reports for each case that will be publicly available, with the intent to make reporting more transparent and complete.
Finally, the FDA announced that it would partner with two U.S. breast implant registries, the PROFILE registry of BIA-ALCL cases, and the National Breast Implant Registry, both run by the Plastic Surgery Foundation.
The FDA did not address in its statement other issues that came up during the March advisory committee hearings, including a panel recommendation to change follow-up imaging from MRI to ultrasound for monitoring women with implants for rupture, and the extensive, off-label use of surgical mesh during breast implant surgery.
FDA approves first vaccine for prevention of dengue disease
The vaccine was approved for children aged 9-16 years who live in endemic areas and have previously had laboratory-confirmed dengue disease.
Dengue is endemic in the U.S. territories of American Samoa, Guam, Puerto Rico, and the U.S. Virgin Islands, according to an FDA statement announcing the approval.
While the first infection with dengue virus typically results in either no symptoms or a mild illness that can be mistaken for the flu, a second infection can lead to a more severe form of the disease, including dengue hemorrhagic fever, which can be fatal. About 95% of hospitalized patients with dengue disease have a second dengue virus infection.
FDA approval of Dengvaxia is based on results from three randomized, placebo-controlled studies of 35,000 individuals in dengue-endemic areas. The vaccine was about 76% effective in preventing symptomatic, laboratory-confirmed dengue disease in people aged 9-16 years with a previous dengue diagnosis. The most common adverse events were headache, muscle pain, joint pain, fatigue, injection site pain, and low-grade fever; the frequency of adverse events decreased after each subsequent dose.
“Infection by one type of dengue virus usually provides immunity against that specific serotype, but a subsequent infection by any of the other three serotypes of the virus increases the risk of developing severe dengue disease. ... The FDA’s approval of this vaccine will help protect people previously infected with dengue virus from subsequent development of dengue disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement.
The vaccine was approved for children aged 9-16 years who live in endemic areas and have previously had laboratory-confirmed dengue disease.
Dengue is endemic in the U.S. territories of American Samoa, Guam, Puerto Rico, and the U.S. Virgin Islands, according to an FDA statement announcing the approval.
While the first infection with dengue virus typically results in either no symptoms or a mild illness that can be mistaken for the flu, a second infection can lead to a more severe form of the disease, including dengue hemorrhagic fever, which can be fatal. About 95% of hospitalized patients with dengue disease have a second dengue virus infection.
FDA approval of Dengvaxia is based on results from three randomized, placebo-controlled studies of 35,000 individuals in dengue-endemic areas. The vaccine was about 76% effective in preventing symptomatic, laboratory-confirmed dengue disease in people aged 9-16 years with a previous dengue diagnosis. The most common adverse events were headache, muscle pain, joint pain, fatigue, injection site pain, and low-grade fever; the frequency of adverse events decreased after each subsequent dose.
“Infection by one type of dengue virus usually provides immunity against that specific serotype, but a subsequent infection by any of the other three serotypes of the virus increases the risk of developing severe dengue disease. ... The FDA’s approval of this vaccine will help protect people previously infected with dengue virus from subsequent development of dengue disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement.
The vaccine was approved for children aged 9-16 years who live in endemic areas and have previously had laboratory-confirmed dengue disease.
Dengue is endemic in the U.S. territories of American Samoa, Guam, Puerto Rico, and the U.S. Virgin Islands, according to an FDA statement announcing the approval.
While the first infection with dengue virus typically results in either no symptoms or a mild illness that can be mistaken for the flu, a second infection can lead to a more severe form of the disease, including dengue hemorrhagic fever, which can be fatal. About 95% of hospitalized patients with dengue disease have a second dengue virus infection.
FDA approval of Dengvaxia is based on results from three randomized, placebo-controlled studies of 35,000 individuals in dengue-endemic areas. The vaccine was about 76% effective in preventing symptomatic, laboratory-confirmed dengue disease in people aged 9-16 years with a previous dengue diagnosis. The most common adverse events were headache, muscle pain, joint pain, fatigue, injection site pain, and low-grade fever; the frequency of adverse events decreased after each subsequent dose.
“Infection by one type of dengue virus usually provides immunity against that specific serotype, but a subsequent infection by any of the other three serotypes of the virus increases the risk of developing severe dengue disease. ... The FDA’s approval of this vaccine will help protect people previously infected with dengue virus from subsequent development of dengue disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement.