FDA considers new efficacy endpoint for diabetes drugs
The US Food and Drug Administration (FDA) on Friday released an updated draft guidance to help sponsors demonstrate efficacy for new antidiabetic drugs and biologics for adults and children with type 1 and type 2 diabetes.The draft guidance replaces a previous version issued in 2008 guidance, which was withdrawn in 2020 because its safety recommendations were outdated. Endpoints related to clinical complications or preventing Type 1 diabetes and issues related to statistical analysis are outside the scope of the guidance.
“Diabetes is a common disease that affects nearly 40 million people in the U.S. and is projected to affect more in the coming years. The need for more antidiabetic treatment options is clear,” said Lisa Yanoff, deputy director of the Office of Cardiology, Hematology, Endocrinology, and Nephrology in the FDA’s Center for Drug Evaluation and Research (CDER). “Today’s draft guidance demonstrates the FDA’s ongoing commitment to providing industry with up-to-date recommendations on how to approach developing new drug therapies.”
FDA announced that hemoglobin A1C, a measure of average blood sugar, will remain an acceptable primary efficacy endpoint.
The guidance states that to adequately interpret clinical trials using this endpoint, sponsors should demonstrate “statistically significant reductions from baseline in A1C that are consistent across trials and relevant subgroups.” In addition, A1C should be measured in a central laboratory using an assay certified by the National Glycohemoglobin Standardization Program.
For most development programs, the primary efficacy endpoint will be a change from baseline in A1C after 6 months of randomized treatment with an additional assessment from baseline at 12 months to assess longer term durability of effect.
New hypoglycemia endpoint
FDA also announced that it is considering a reduction in the risk of hypoglycemia, or low blood sugar, to be a clinically relevant outcome measure for these trials alongside a reduction in or maintenance of an acceptable A1C value.
FDA states that “in contrast to the extensive experience with A1C as an efficacy endpoint, hypoglycemia endpoints have primarily been used to evaluate safety and (at the time of publication of this guidance) have only rarely been used as endpoints for comparative claims (i.e., efficacy, comparative safety).”
For patients with diabetes mellitus, FDA considers level 3 and level 2 hypoglycemia acceptable endpoints to support claims related to improvement in glycemic control. Level 3 is severe hypoglycemia characterized by altered mental or physicals functioning while Level 2 is a blood glucose level less than 54 milligrams/deciliters (mg/dL).
The deadline for submitting comments is 24 August 2023.
In March 2020, FDA issued a draft guidance focused on evaluating the safety of drugs for Type 2 diabetes mellitus. (RELATED: FDA Revamps Safety Testing for New Type 2 Diabetes Drugs, Regulatory Focus 9 March 2020).
Draft guidance
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