Flexible Endpoints Key to Successful Rare Disease Drug Trials

Jonathan Goldsmith, MD, Associate Director of the Rare Disease Program of the Center for Drug Evaluation and Research at FDA

Jonathan Goldsmith, MD, Associate Director of the Rare Disease Program of the Center for Drug Evaluation and Research at FDA

“What’s clinically meaningful to patients?” Jonathan Goldsmith, MD, associate director of the Rare Disease Program of the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA) asked the attendees of the FDA/CMS Summit in Washington, D.C. this week.

When developing a clinical trial for a rare disease, Goldsmith encouraged looking for novel endpoints, as in those that would make a patient’s life better.

Applauding FDA’s flexibility working with industry on orphan drug approvals, Ron Cooper, president and CEO of Albireo Pharma, said his firm is focused on attacking pediatric liver diseases. After identifying the correct endpoints, based on the patient population’s most acute needs, Albireo was able to complete a trial in six months. “A traditional study would have taken years, requiring many patients,” Cooper said. “[That’s] not viable for people who need something quickly.”

Even as a relatively narrow endpoint focus is important to speed rare drug trials, Cooper reminded the audience that the totality of the data generated by a trial is important, too. Natural history data can supplement “what we’re doing in clinical trials,” he added.

FDA’s Goldsmith noted that, in some cases, data on natural history and external controls can serve as a de facto control group. Under that scenario, FDA “might accept a trial without a placebo,” he said.

Regulators are already doing a pretty good job in this arena, Goldsmith said. Nearly 20% of rare drug approvals over the last several years have been for drugs for populations under 5,000, he noted. “I think we’ve been very good” working with drug manufactures to speed the approval process, he said.

At the same time, Goldsmith acknowledged that FDA’s attention can be shifted if it’s presented with an application for a drug impacting a broader patient population, such as diabetes. “We only have so many resources,” he explained.

Author: Michael Causey