FDA committee unanimously rejects GLP-1 implant for type 2 diabetes
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In a hearing on September 21, an FDA committee rejected an implantable device capable of delivering a GLP-1 receptor agonist for adults with type 2 diabetes.
The FDA Endocrinologic Metabolic Drugs Advisory Committee voted unanimously, 19-0, to reject ITCA 650 (Intarcia Therapeutics). The investigational device consists of a miniature pump implanted within the skin that can deliver exenatide (Bydureon/Byetta, AstraZeneca) to adults with type 2 diabetes. As Healio previously reported, in the FREEDOM-1 study published in 2017, ITCA 650 was associated with a greater reduction in HbA1c and body weight than placebo for adults with type 2 diabetes. A greater reduction in HbA1c with ITCA 650 was also observed in a small study, published in 2018, of adults with uncontrolled type 2 diabetes and a high baseline HbA1c.
However, on Sept. 21, the FDA’s Endocrinologic Metabolic Drugs Advisory Committee rejected the device citing safety concerns associated with acute kidney injury and cardiovascular outcomes that committee members said outweighed the benefits of the device. The vote followed two prior complete response letters that rejected the device in 2017 and 2020, according to a slide from the meeting.
The concerns about acute kidney injury stemmed in part from safety data during trials. In pooled data from three trials, 1.8% of adults randomly assigned to receive ITCA 650 experienced an acute kidney injury event compared with 1% of those receiving either placebo or an active comparator. Some committee members recommended the risk for acute kidney injury be assessed in a comparator trial with another GLP-1 receptor agonist.
“I do recognize that the absolute risk [for acute kidney injury] is low, and I do believe in my heart that there should be a way to mitigate it and treat it quickly,” Patrick H. Nachman, MD, committee member and director of the division of nephrology and hypertension and professor of medicine at University of Minnesota, said during the meeting. “But the time to find out how to mitigate the risk is before approval, not afterward.”
Regarding CV safety, data presented during the hearing showed ITCA 650 met the FDA’s guideline for pre-approval CV outcomes trials. In a pooled meta-analysis of three trials, ITCA 650 was non-inferior to placebo for assessing risk of primary major adverse CV events. However, committee members said a larger study needed to be conducted.
“I’m particularly concerned about the potential for CV harm, which there was a signal in the FREEDOM trial,” Connie B. Newman, MD, committee member and endocrinologist and adjunct professor of medicine in the division of endocrinology, diabetes and metabolism at New York University School of Medicine, said during the meeting. “What I think could be done is more data, perhaps a premarket CV outcomes trial that is appropriately powered and also assesses acute kidney injury.”
Some committee members also expressed concerns about medication variability and said additional studies that examine glycemic excursions and how they are related to medication level would be helpful.
“The device itself seems to have great potential. If operating at a very good level, I could really see it as a game changer,” Robert Greevy, PhD, committee member and professor of biostatistics at Vanderbilt University, said during the meeting. “I am also not convinced, given the data that were presented, that we’ve seen the best version of this device. There appears to be evidence that the dispensing of the medication is not consistent, and we didn’t see any data to explain why that could be.”
References:
- Henry RR, et al. Diabetes Care. 2018;doi:10.2337/dc17-1519.
- Rosenstock J, et al. Diabetes Care. 2017;doi:10.2337/dc17-1306.
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September 21, 2023 FDA Endocrinologic and Metabolic Drugs Advisory Committee. Available at www.youtube.com/watch?v=Z2AMqC4ldNM. Published Sept. 21, 2023. Accessed Sept. 22, 2023.
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