Newsdio, March 12, 2020

The United States Food and Drug Administration (FDA) has published new proposed guidance to the industry on assessing the safety of type 2 diabetes newer medications and withdrawn the 12-year “outdated” conditions for standardized cardiovascular outcome trials (CVOT).

The new proposal guides, “Type 2 Diabetes Mellitus: evaluating the Safety of New Medications to Improve Glycemic Control,” will exchange the December 2008 needs that manufacturers implement CVOT to eliminate an intolerable risk of cardiovascular safety. That alters followed issues expressed at the time about the thiazolidinedione class of glucose-lowering drugs.

Thereafter, the FDA has examined the results of several (CVOTs) conducted to comply with the December 2008 guidance recommendations. According to the federal registry announcement, none of the CVOTs up to now have detected an enhanced risk of ischemic cardiovascular events; some of the CVOTs have found a lower risk for cardiovascular events.

In October 2018, the FDA’s Endocrinological and Metabolic Drug Advisory Committee barely supported (10 to 9) to continue to require CVOT, but the majority of panel members also advised some changes which include more safety data requirements beyond cardiovascular events.

The FDA is examining the recommendations of the December 2008 guideline and is now offering a revised method to analyze the safety of new drugs and biologics to improve the glycemic control, based on CVOT results over the years and the panel’s recommendations, “

The FDA stated that the new draft proposal does not involve a recommendation that the sponsors of all new therapies for type 2 diabetes consistently eliminate a specific degree of risk of ischemic cardiovascular adverse outcomes.

Otherwise, the proposal requires at least 4,000 patient-years of exposure to the new drug in phase 3 trials and incorporation of study subjects with comorbid conditions and/or complications of diabetes, including minimum 500 with stage 3 chronic kidney disease, 4, 600 with determined cardiovascular disease, and minimum 600 over 65 years.

The FDA is requesting stakeholder input on these and other issues, including study duration, topic demographics, specific safety concerns, and event adjudication.

In a statement, Lisa Yanoff, MD, acting director of the Division of Metabolism and Endocrinology Products at the FDA’s Center for Drug Evaluation and Research, stated that By following prior FDA recommendations, contributors have demonstrated that the new drugs for type 2 diabetes are not extremely risky for ischemic cardiovascular disease, which has granted encouraging cardiovascular safety evidence for millions of diabetes patients. Presently, with this proposed method, more comprehensive and valuable safety information for these medications can be provided.