Endocrine Insider
July 10, 2008

The Endocrine Society President-Elect, Robert Vigersky, MD, testified before the Food and Drug Administration (FDA) Center for Drug Evaluation and Research's Endocrinologic and Metabolic Drugs Advisory Committee on July 2, 2008 about the need to include long-term cardiovascular impact research in the study of all new diabetes drugs. The advisory committee held a two-day hearing that included expert witness testimony and public testimony on the role of cardiovascular assessment in the pre-approval and post-approval settings for drugs and biologics developed for the treatment of type 2 diabetes. 

Dr. Vigersky testified that the Society believes that a two-stage approach should be considered in the approval process for all new diabetes medications. Pre-approval studies should be designed to capture surrogate glycemic and cardiovascular end-points, as well as both adverse clinical endpoints and beneficial clinical outcomes. Drugs showing appropriate glycemic effects without an adverse short-term cardiovascular outcome should achieve "conditional" approval, with labeling reflecting the interim nature of the results, allowing the drugs to reach the market and benefit patients. After a specified period of time, the clinical macrovascular results could be evaluated and final approval granted with those results included in the new label. The Society recommends that improved macrovascular outcomes should not be a requirement for final approval, but that worse macrovascular outcomes would be grounds to rescind conditional approval or require the inclusion of a Black Box warning. Because of the substantial additional expense that such studies would engender, the FDA may consider granting additional years of market exclusivity for the drug as a reasonable offset to the costs. The full testimony may be viewed here.

The advisory committee heard from a number of clinicians and researchers in the field of diabetes who independently outlined a variety of factors that must be considered when determining the role of cardiovascular assessment in pre- and post-approval settings for drugs and biologics developed for the treatment of type 2 diabetes. Many of the expert witnesses expressed their support for monitoring cardiovascular effects of diabetes drugs but felt that drug approval should not necessarily be contingent on the cardiovascular results. 

Following expert witness testimony, the advisory committee voted in favor of requiring that studies for all new diabetes drugs or biologics include a long-term cardiovascular trial or provide other equivalent evidence to rule out unacceptable cardiovascular risk. While 14 of the 16 advisory committee members were in favor of this requirement, opinions diverged on whether the study should be conducted pre- or post-approval, and the committee did not issue a clear-cut recommendation during the hearing. The advisory committee will provide its recommendation to the FDA, which will make a final decision on the role of cardiovascular outcomes measurement in clinical trials for new diabetes drugs.