Cardiovascular safety issues with a number of drugs led the Food and Drug Administration (FDA) in late 2008 to introduce new regulatory guidelines for type 2 diabetes drugs and more recently to recommend a risk assessment and mitigation strategy for rosiglitazone. Consequently, as a recent article in the Journal of Contemporary Clinical Trials noted, the “immediate effect of the guidelines was a pathway to approval fraught with greater challenges.”
Accordingly, the authors of the study, Viereck and Boudes, examined the impact of FDA’s 2008 guidelines for addressing cardiovascular risks of new therapies for type 2 diabetes on clinical trials. They focused on the new class of incretin-modulating drugs, exenatide, sitagliptin, saxagliptin and liraglutide, which were approved in 2005–2010.
They then contrasted these findings with those from 2 different groups: 1) diabetes drugs approved in the same timeframe but with a non-incretin mechanism of action (colesevelam HCl and bromocriptine mesylate) and 2) diabetes drugs with NDAs delayed and not yet approved within the same timeframe (vildagliptin, alogliptin, insulin inhalation powder, and exenatide long acting release).
Based on their study, the authors concluded that, “the new guidelines have had an important impact on clinical development.” Specifically, they found that the drug “review time has increased over 2-fold,” and “the increase is seen even if a drug with the same mechanism of action has been already approved.” In addition, “the number of randomized patients and patient-years in NDAs increased more than 2.5 and 4 fold, respectively since the guidelines.”
Ultimately, through rigorous methodology, Viereck and Boudes quantitate for type 2 diabetes drugs what many have intuitively thought: huge increases in clinical trial size, NDA and review times as a result of new cardiovascular guidelines for drugs in type 2 diabetes. The increased regulatory burden relative to the EU is stifling innovation in the US. Accordingly, the authors concluded that, “the significant cost increases and negative publicity because of rare adverse reactions will adversely affect future clinical research in type 2 diabetes and not address its burgeoning health care impact.”