[Welcome to the Director's Corner, an audio podcast series featuring the Director of FDA Center for Drug Evaluation and Research. ]
Colleen Labbe: Hello. I'm Colleen Labbe from the CDER Office of Communications. For two decades, CDER has used certain methods to speed drug development and the regulatory review process so that promising therapies can get to patients faster. Today I'm talking with Dr. Janet Woodcock to learn more about one of these pathways, the breakthrough therapy designation. Thanks for joining me again today, Dr. Woodcock.
Janet Woodcock: Happy to be here.
Colleen Labbe: So, let's first describe exactly what the breakthrough therapy designation is and what it means in the context of drug development.
Janet Woodcock: Well, the breakthrough therapy designation is one of four pathways that were designed to prioritize drug development or regulatory review to allow more timely availability of drugs for serious and life-threatening conditions primarily, or [for] public health advances. The other three besides breakthrough therapy designation are priority review, which speeds up the review, accelerated approval, which is approval based on a surrogate endpoint, and a fast track, which is another designation. A drug that receives breakthrough therapy designation may also receive fast track designation and may get a priority review as well, or be approved under accelerated approval, but these are all different.
Now, breakthrough therapy designation was started in 2012 by Congress, and the term breakthrough therapy refers to a drug candidate that's currently in clinical development, in people, that shows early promise in treating a serious condition. The criterion there is that preliminary clinical evidence suggests that the investigational drug may provide a substantial improvement over available therapies for a clinically relevant endpoint. That means something that means something medically. And, it's more accurate, really, to describe these as potential breakthrough therapies because of course they haven't been proven yet, but the designation is intended to help things along so that you can get that proof.
Colleen Labbe: Okay. So how does a drug candidate qualify for the designation?
Janet Woodcock: Well, generally, the drug sponsors, people developing the drugs, can apply for breakthrough designation while the drug is still in early clinical testing phases and they would have collected data, maybe response of a cancer to the drug, or other kind of data in other diseases, that suggest that the drug may provide this substantial improvement over what is currently available for treatment of that serious condition. A decision to grant breakthrough status is somewhat of a judgment call because substantial improvement, of course, is a little bit subjective. Sometimes we see improvement in a life-threatening disease, right, but it may not be huge improvement. But if the people are dying, and it prolongs their life, then that seems rather important of course.
Colleen Labbe: Of course. Yeah.
Janet Woodcock: And, so, we have to think about, we have to take into account the available evidence, the severity of the disease, the unmet need, and then the size of this affect that's been observed as preliminary data. And, it's important to note that for a drug candidate to get breakthrough therapy status, it does not have to be curative or even perhaps dramatically better than existing therapies, but it does have to be substantially better. Often in their development programs, companies will be comparing the new drug to the current standard of care in an early clinical trial if there's a standard of care available. We might consider, if there isn't really much of a standard of care, we can consider historical data or concurrent, contemporaneous historical data, especially when a clinical course is well understood. For example, in advanced cancers we know that there isn't a very high rate of reversal where the cancer spontaneously remits and so forth. And so, we can pretty much see if there's a big response to the intervention in advanced cancer, that that really is an affect of the drug.
Colleen Labbe: Okay. What exactly are the benefits of the designation?
Janet Woodcock: Well, one of the things that's confusing to people is people feel that breakthrough therapy lowers the approval standard, and I want to say that isn't true at all. What the designation is supposed to do is allow sponsors to get greater input from the FDA staff because we feel if this is a big advance for a serious disease, we need to work with the drug developer to move that along as efficiently as possible. So basically, they get more attention. Senior management and others get directly involved to advise on what the further clinical development program trial should look like, guide the process, and ensure that across all the involved disciplines, there is efficiency, and we try to move things along. So, we can advise sponsors on what analyses to do, study size, methodology and different other components. We call it an all-hands-on-deck. When you see something like this, you really want to get all hands on deck and everybody help to move this through. Now sometimes, I have to stress, you do this evaluation of the breakthrough and it doesn't pan out, and we can withdraw that designation if that's the case. It doesn't mean that everything that looks promising when it's further evaluated is actually going to be a significant advance. But we feel that if it looks promising, we owe it to the patients, we ought to move this along, get it evaluated and see whether or not it is a big advance.
So, if at the time of submission, once they've done a further evaluation, we determine that the drug would lead to a significant improvement in a condition, based on data the sponsor has provided, then we give the application a priority review. This reduces the review time from 10 months to 6 months. But we do this for drugs that don't have breakthrough designation also if they appear to have a public health advantage or a significant improvement. And, as I said, it does not alter the standard for approval. That's a very important thing for people to remember.
Colleen Labbe: So tell us about how the program has been going since it first began in 2012 and what we expect in the future.
Janet Woodcock: Well, the program has been very popular from the beginning and continues to grow. When the designation was first started, we received a lot of requests. A lot of them were rather late in the development cycle though, and we couldn't give a lot of help because most of the development program had been completed.
We have received hundreds of requests [since] 2012. For perspective, in 2014 and 2015, 22 percent of drugs that we approved were designated as breakthrough therapies, and by 2017, 37 percent had been designated as breakthrough therapies. I think it's important to recognize this didn't come from specifically the breakthrough designation program. This came at the same time as a revolution in drug development with targeted therapies, personalized medicine, new types of interventions. And so, all these things came together to make this change in drug development. We do think the program will continue to grow and will facilitate shortened development times and earlier availability for patients who really have run out of options or don't have any good options. I think this really is good news for patients and that's what was intended.
Colleen Labbe: Definitely good news for patients. Well, Dr. Woodcock, thanks again. It's always a pleasure speaking with you.
Janet Woodcock: Thank you very much.
[Thanks for listening. For more information about what you heard today, please visit our website at FDA.gov/drugs. ]