platform trials to answer many questions about a drug, Woodcock said. Precision medicine factors into this approach because a patient can be matched to a therapy and a trial based on his or her genetics.
In an “umbrella trial,” different drugs are tested on patients with different genetic mutations. Woodcock said the advantage of an umbrella trial is the ability to recruit patients and not kick them out of the study because they are ineligible. Instead, patients can be assigned to different arms. Oncology is leading the way in umbrella trials, Woodcock said.
Woodcock’s support of alternative approaches to testing drugs has sparked some controversy. One example is the 2016 approval of a Sarepta Therapeutics (NASDAQ: [[ticker:SRPT]]) drug, eteplirsen (Exondys 51), for the rare muscle-weakening disease Duchenne muscular dystrophy (DMD). The Cambridge, MA, biotech tested in a randomized, placebo-controlled trial. But for reasons more financial than scientific, Sarepta enrolled just 12 patients—eight who were given the drug one group of four given placebo. Sarepta later excluded two patients who had received the drug who lost their ability to walk, further shrinking the size of the study. That small study compared the tiny group to historical data of similar Duchenne patients.
FDA documents released last August described conflict within the agency regarding the Sarepta drug. Senior FDA officials questioned whether Sarepta’s small study really showed that the drug helped patients, and many staffers voted to reject eteplirsen, fearing approval could set a precedent for other rare disease drugs. But Woodcock concluded that the drug was “reasonably likely to predict a clinical benefit” and met the agency’s standards for the accelerated approval of drugs that treat serious and rare conditions with no approved treatments. Robert Califf, FDA Commissioner at the time, sided with Woodcock.
Woodcock did not address the Sarepta decision at the conference. But her comments suggested she wants to head off similar confrontations. If a company wants to use a novel clinical trial design, Woodcock said it’s best to talk about that with the FDA outside of the context of a specific drug. That way, the discussion can focus specifically on the design of the clinical trial.
Califf, who joined Woodcock onstage following her presentation, added that if a company waits until there’s a drug on the line to discuss a novel clinical trial design, patients and investors will also have a stake in the outcome. At that point “there’s no way you can be perceived as an unbiased advocate for something,” he said.
Both Califf and Woodcock said that going forward, the information used to evaluate drugs will come from multiple sources, not just clinical trials. The FDA does not have all of the knowledge, Califf said. Patient communities, scientists, and clinicians will weigh in. That doesn’t mean that randomized clinical trials are going away. Randomization is a way to make sure that researchers don’t influence a trial’s conclusions, Woodcock said. But under certain circumstances, different trial designs are more appropriate.
“In this world of small subgroups, we’re going to have to rethink how we do these analyses,” Woodcock said.
Photo by Flickr user University of Michigan School of Natural Resources & Environment via a Creative Commons license.
