How FDA's Breakthrough Therapy Designation Program Changed the Rare Disease Space

On July 9, 2012, officials signed the Food and Drug Administration Safety and Innovation Act (FDASIA) which had a section within it that established a new designation—the Breakthrough Therapy Designation—which allows for expedited development and review of drugs to treat serious or life-threatening diseases if substantial evidence is provided.

The concept for the designation was first initiated at an annual meeting held by Friends of Cancer Research, an organization that has been instrumental in the development and implementation of policies dedicated to ensuring that safe and effective treatments are available to patients who need them most as quickly as possible.

At the National Organization of Rare Diseases’ Rare Diseases & Orphan Products Breakthrough Summit (NORD Summit), Rare Disease Report^® sat down with Ellen Sigal, PhD, the chair and founder of Friends, to discuss how she and her organization were able to turn an ambitious concept into reality and what this designation did for the rare disease community as a whole.

RareDR: Can you tell us more about the expedited FDA development program?

Ellen Sigal, PhD: We always have a conference every year that includes the US Food and Drug Administration, the National Cancer Institute, and other stakeholders, and Rick Pazdur, MD, suggested to us that we should look at—we didn’t call it breakthrough—what we should do in the regulatory environment when we see substantial evidence early?

It seemed like an easy question, but the answer was very complicated. We worked with many stakeholders, companies, statisticians, and scientists, and we came up with a whitepaper on it—but it wasn’t easy, because the questions were hard. For example, what does substantial evidence mean? Because in every disease setting, it’s very different.

But in any event, we reached a consensus and then we put it through legislation. And at that point, we thought that maybe there would be 1 or 2 drugs per year, and we thought they would all be for cancer, so we were pretty shocked at the outcome; it was unexpected.

What we’re very pleased about, is it created this new pathway that is built on evidence and many diseases have benefitted from it. I think it’s still 55% to 60% cancer, but there’s a large percentage of rare diseases and other diseases that have benefitted from this designation.

What was the process of turning that concept into a reality?

The process was first deciding what ‘substantial evidence’ means; every disease setting is different—what this means in breast cancer is different than what it means in glioblastoma or pancreatic cancer. We were trying to look for definitions and it was very complicated. But we knew that the processes had to change, so when we brought it to legislation a lot of members of Congress thought, ‘Well, they can already do this’ and the answer is, ‘Maybe, but not so quickly.’

So what Breakthrough did, was it changed the way the FDA handled it, it changed the way academics and others handled it, it changed the culture among companies and among people because they started doing better, smarter trials that would really look for evidence earlier on.

And, of course, everybody thought they had a Breakthrough—it was like everyone’s children are brilliant and beautiful—but it was really game changing and part of it was because it was a better process that defined but it was because it really meant substantial evidence and all-hands-on-deck.

How has this law impacted patients and providers in the rare disease space?

Breakthrough changed cultures—companies, FDA, NCI—but cancer is a rare disease, so 30 years ago when we started the war on cancer it was 1 disease; now, we know it’s hundreds and hundreds of diseases and within subsets of cancer there are rare diseases. For example, we have some in lung cancer with squamous cell, which may be 2% of a population.

So clearly, we’re really looking to affect those populations in or outside of cancer whether there are no obvious large trials necessary or possible. And so, that was really a major impact on rare diseases—many of them in cancer, but many of them outside of cancer.