FDA Regulation of Drugs, Devices for Diabetes

San Diego—During a symposium at the ADA meeting, a pharmaceutical industry executive and a US Food and Drug Administration (FDA) official provided their views on the pharmaceutical industry and how regulations and an increased concern with safety will affect drug development.

Mark S. Fineman, MS, MAS, vice president of development for Elcelyx Therapeutics, Inc, expressed gratitude for the FDA, calling the organization’s job “the most difficult and daunting job in the drug development process.” For instance, he said, the agency’s scope involves regulating disparate products such as eggs, bandages, cancer drugs, and artificial hearts. As the scope grows, the FDA is not receiving additional funding, according to Mr. Fineman, creating a difficult environment. He mentioned a few FDA initiatives focused on safety, including the Prescription Drug User Fee Act that provided funds for postmarketing surveillance and the Risk Evaluation and Mitigation Strategy program as well as a 2008 recommendation that manufacturers of type 2 diabetes drugs provide evidence that the therapies will not increase the risk of cardiovascular events.

Although Mr. Fineman supports the FDA’s higher safety scrutiny, he said companies are concerned with the longer and unpredictable review times and the high investment costs, which could lead to fewer firms willing to take the risks associated with developing drugs. He cited research that found venture capital investing in biotechnology, medical devices, and equipment has declined in recent years. In 2007, venture capital firms invested $5.27 billion in biotechnology and $3.75 billion in medical devices and equipment compared with $3.69 billion in biotechnology and $2.32 billion in medical devices in 2010. Mr. Fineman said the worsening economic conditions attributed to some of the reduced funding, but he also said companies are less willing to invest in new drugs because of the uncertain regulatory environment. “This is something that will have an impact for at least a decade,” Mr. Fineman said. “It’s clear there’s no easy fix [to the problems]. Industry and the FDA must work together. We need to refine the process.”

Douglas C. Throckmorton, MD, deputy director of the FDA’s Center for Drug Evaluation and Research, provided recent trends in diabetes treatment. Until the mid-1990s, patients with diabetes had 2 options: insulin or sulfonylurea. Currently there are 11 drug classes to treat diabetes, which Dr. Throckmorton said is helpful because the disease progresses over time and patients are treated throughout their lives. Like Mr. Fineman, Dr. Throckmorton discussed the December 2008 recommendations concerning cardiovascular risk in new antidiabetic therapies. He said the FDA assesses cardiovascular risk by comparing the rates of cardiovascular events for the new drug with a control group through meta-analysis or a single, large phase 3 trial. Since the FDA issued the guidance, Dr. Throckmorton said there has been no decline in the number of commercial investigational new drug applications for diabetes drugs. From January 1, 2006, through November 30, 2008, there were 63 applications. From December 1, 2008, through June 24, 2011, there were 70 applications. Still, Dr. Throckmorton mentioned a few challenges in drug development.

Study investigators sometimes have problems keeping patients in the trials due to worsening glycemic control. He also said it is difficult to choose an appropriate cardiovascular end point as well as the right control group. The FDA has taken a few steps to support innovation in drug development. Last year, the organization issued a draft guidance on using adaptive designs in trials. The FDA is also planning on releasing recommendations concerning the use of trial-enrichment designs as well as meta-analyses. Dr. Throckmorton discussed a collaboration between the FDA and Duke University called the Clinical Trials Transformation Initiative (CTTI) that is focused on improving trials through quality measures, avoiding duplication and waste, and improving training and procedures. He said that the FDA is also working with Pfizer, Inc, on a CTTI pilot project for a phase 3 trial.