The breakthrough drug designation, patients driving progress

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Published: 9 Jul 2018
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Dr Ellen V. Sigal - Friends of Cancer Research, Washington D.C., USA

Dr Sigal speaks with ecancer at the 2018 WIN symposium about her experience in patient care, and implementing science in policy.

She starts by discussing the Breakthrough Drug Designation which accelerates the approval breakthrough drugs based on preliminary evidence.

Dr Sigal also discusses the Lung-MAP trial and the integral involvement of patients in all of the work she does.

Our work is traditionally in the United States but we were asked to speak and I’m very happy to come here and speak about what’s going on in our world and what’s going on in the world of policy. So today I’m going to speak about the evolution of advocacy – where it started, where it is now, the evolution of patient-centred care, what that means, defining what patient-centred care means. There’s a lot of discussion on it but not a lot of definition to it. Then I’m going to discuss a policy and how policy happens in Washington and how you implement science into policy and what that process is. We’re going to give three examples: the Lung-MAP Master Protocol, Breakthrough Drug Designation and the integration of the Oncology Centre at FDA.

What is the Breakthrough Drug Designation?

The Breakthrough Drug Designation is a policy decision that we were able to get into law, into statute. It simply started with the FDA asking a very simple question – what should we do when we see substantial new evidence in a drug? What should we do? It seemed like it was pretty obvious but it wasn’t obvious and it took us about a year to work with all sectors, companies, scientists, regulatory agencies, the National Cancer Institute, to make recommendations because, as obvious as it was, it really isn’t obvious in every disease setting. If you ask a statistician that question they’re going to give you a different answer; if you ask a patient it’s going to be different and every disease setting is very different. So ultimately we published a white paper and then decided to bring it into legislation; it was part of the Drug User Fee six years ago in Congress and it’s a statute. What it did initially is we thought it would be two drugs a year, mostly cancer. Now, four years later, it’s 250 drugs and it’s cancer is 60% so it changed behaviour.

How are patients involved in that?

Patients are involved in everything we do. Patients are the North Star, they’re the centre of what we do. So we ask patient groups what are most important to you? What are the outcomes you’re looking for? Patients clearly want to get treatments that have efficacy and that are most likely to work for them, so when we ask patients we ask them levels of risk, levels of tolerability, whether they have one or two biopsies, what outcomes are they most interested in. Of course, that varies because when a patient has early stage prostate cancer or breast cancer their risk elements are going to be very, very different from late stage glioblastoma or pancreatic cancer or lung cancer. So it’s not one easy answer and the evidence, based on what regulatory standard, will vary also. But certainly the patients are willing to take more risk, depending on their stage of cancer.

What do we really mean with the term ‘breakthrough’?

Good question, a very complicated answer. Breakthrough, first of all, is a legal statutory definition in statute in the law. So essentially Breakthrough Designation is what the FDA can give a drug if they see substantial early evidence. The way they decide that depends on the disease state and the preliminary evidence but it has to be substantial. It doesn’t mean if they get the designation that they will get approved. Now, of course, for a patient that is a little bit confusing and for the media it’s confusing because it means there is substantial early new evidence that was unexpected. In many cases it does work out and the drugs do get a final designation but in some cases the evidence isn’t substantial at the end after the phase II or phase III and they do not get the designation. But it means that there is new evidence that is interesting, worthy of pursuing.

Tell us about the Lung-MAP trial.

Lung-MAP Master Protocol, that is a lung cancer trial. We started off with squamous cell, it is now all histologies. It’s a public-private partnership between the National Cancer Institute, the Foundation for NIH, Friends of Cancer Research and multiple pharmaceutical companies. Essentially that’s a genomic driven trial where patients with specific biomarkers are given specific treatments based on those biomarkers. Those that don’t have a biomarker are given immunotherapy. So everyone who is screened, there is a genetic screening, we’re using the Foundation Platform, will have an arm. Many of the frustrations for patients in rare diseases is they’re, in some cases, 2%, 5% of the population and it’s very, very, very difficult to find these patients and many of them who are screened don’t have one of these mutations and then they don’t have a trial. This trial has an arm for all patients; it is late stage, it’s refractory but it’s also a registration trial.

How does all of this resonate with the WIN missions?

It’s exactly compatible. The Lung-MAP, although we are in over 600 sites in the United States and in Canada, we’re really, with the exception of Canada, not an international trial. Most of the work that we do at Friends is really based on the United States so the fact that we are breaking down silos in the international part of what WIN is doing is extremely interesting to us and very important.

What would your take home message be?

The take home message is that the patient is always the North Star, working together, taking down barriers, being audacious. And the urgency and passion the patients feel but they have to be scientifically rigorous and it has to be meaningful for patients. So the idea of working together is really important.