Study: FDA Flexibility Helps With Orphan Drug Approvals

May 8, 2015

The FDA is not requiring ordinary proof of effectiveness as it strives to approve orphan drugs for some 7,000 diseases, only 300 of which currently have treatment options, a new study concludes.

The authors, Frank J. Sasinowski, Erika B. Panico and James E. Valentine, looked at 27 noncancer orphan drugs approved between July 1, 2010, and June 30, 2014. They found that two-thirds of sponsors bringing these drugs through the FDA won approvals, despite not providing the gold standard of proof of safety and effectiveness, according to the study in Therapeutic Innovation & Regulatory Science.

Generally, before approving a drug, the agency likes to see evidence from two well-controlled and randomized clinical trials that the therapy has met its primary endpoint. However, the FDA Modernization Act and accelerated approval allow the agency to approve a drug that reasonably can be assumed to provide clinical benefit based on one trial, with confirmatory trials conducted later.

During the four years studied, 14 of the 27 drugs — 52 percent — were approved in this way, the authors say. Another five drugs were approved using “case-by-case flexibility,” which allows the FDA to approve drugs that had not been proven safe and effective in two trials or would not be considered an acceptable single-study approval or an accelerated approval.

In two instances involving the 14 approvals, the FDA applied both types of flexibility, a condition the authors refer to as “flexibility squared.” Basically, that means that the FDA granted both of these drugs accelerated approval based on just one pivotal study, with a surrogate or intermediate clinical endpoint used to assume clinical benefit, the authors say.

Even when it came to the eight orphan drugs granted regular approval, the FDA chose to exercise some level of flexibility, the authors write. While one of these orphan drugs was supported by the traditional two clinical trials, the demonstrated effects were on a surrogate endpoint, rather than one that demonstrated a direct clinical benefit.

This is a good thing, the authors say, as more than 30 years have passed since the Orphan Drug Act was passed and many Americans with rare diseases still are without any therapeutic options.

The very nature of orphan drugs and rare diseases means that applications often don’t come with the same amount of data that you might see with a well-publicized condition like hypertension or diabetes, lead author Sasinowski, an attorney at Hyman, Phelps & McNamara and a former FDA official, said.

The fact that the FDA has found creative ways of making treatments available to patients who often have no therapeutic options is an overwhelmingly positive thing — not only for those patients, but for Wall Street analysts and venture capital firms and even the FDA itself, Sasinowski says.

Read the study at www.fdanews.com/05-04-2015-orphandrugapprovals.pdf. — Lena Freund