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Sept. 21 from an advisory committee of the Food and Drug Administration.
The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.
“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
“No evidence of improved adherence”
Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.
However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
Seven years of FDA review
This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.
Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week.
But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”
All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Sept. 21 from an advisory committee of the Food and Drug Administration.
The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.
“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
“No evidence of improved adherence”
Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.
However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
Seven years of FDA review
This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.
Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week.
But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”
All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Sept. 21 from an advisory committee of the Food and Drug Administration.
The 19 voting panel members mostly cited concerning signals of both renal toxicity in the form of excess episodes of acute kidney injury (AKI) as well as increased cardiovascular events compared with placebo as their main reasons for voting that the developing company, Intarcia Therapeutics, had not shown adequate evidence that the benefits of the drug-device combination, known as ITCA 650, outweighed its risks for treating people with type 2 diabetes.
“I’m quite uncomfortable with the AKI safety,” said panel member Erica Brittain, PhD, deputy chief of the Biostatistics Research Branch of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
The case that ITCA 650 is ready for routine use was also undermined by uncertainty documented by FDA staff about the uniformity and reliability of exenatide delivery by the DUROS device, a matchstick-sized reservoir that’s placed subcutaneously and designed to deliver exenatide continuously for 6 months at a time, noted Cecilia C. Low Wang, MD, chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.
“No evidence of improved adherence”
Another shortcoming was no data on the impact that this form of drug delivery, first developed and FDA approved to treat patients with prostate cancer with leuprolide acetate, really accomplished its goal of improving adherence to a glycemic-control agent. Intarcia Therapeutics presented “no evidence of improved adherence,” said Dr. Low Wang, director of the Glucose Management Team at the University of Colorado Hospital.
However, she and several other panel members acknowledged the compelling comments from several patients and health care professionals experienced in using or administering the device who, during the public comment period, voiced anecdotal testimonials to its positive impact on treatment compliance.
Seven years of FDA review
This review of ITCA 650 capped a nearly 7-year effort by Intarcia Therapeutics to receive marketing approval for ITCA 650 from the FDA, which began with an application filed in November 2016 (and denied by the agency in September 2017). Intarcia resubmitted an amended application in 2019 that the FDA again rejected in 2020. The company’s persistence following that led to the current panel meeting, the first time the ITCA 650 evidence came before an advisory panel.
Committee members in general praised the concept of managing blood glucose by continuous release of a medication 6 months at a time. They also offered ideas on a path forward, such as a study that used an active competitor. Ideally, that could be another agent from the same class of GLP-1 receptor agonists such as Bydureon, an injected formulation of exenatide administered by subcutaneous injection once a week.
But the key, agreed panel members, was to bulk up the evidence that ITCA 650 is safe. “The data show concerning safety signals that need further investigation,” summed up Dr. Low Wong. “There are concerns about overall safety, all-cause mortality, AKI, cardiovascular events, and glycemic excursions.”
All voting members of the advisory committee met the FDA’s standard for having no relevant financial relationships.
A version of this article appeared on Medscape.com.