November 5, 2013 - This year’s ASH meeting is following in the wake of the first approval under breakthrough therapy designation (BTD), an FDA program intended to expedite the development and review of new medicines for serious conditions with unmet needs.
The stakes and the expectations are high. When BTD was created in July 2012, it represented the first major revision to the FDA’s review process in more than a decade. Big questions are circulating. Will BTD live up to the hype? And how will we continue to keep patients safe while pursuing ever-faster development and review?
I’m often asked about these big issues as well as the details, and I think now is a great time to reflect on the current state of BTD and the progress we are making toward fulfilling its potential. And, in case you missed it, I wrote about the importance of BTD a few months ago. You can read about it here.
Science fuels progress
To date, the FDA has granted 30 BTDs (full stats are available on the FDA website) - that’s about 12 more than when I first wrote about the program back in June. Cancer medicines have received the lion’s share – nearly half of the publicly announced designations are for some form of cancer.
These numbers not only reflect the need for new cancer medicines – they illustrate the great progress being made in cancer research.
And that’s what BTD is all about. Faster scientific progress was the catalyst that prompted everyone to act. Patients and advocates, Congress, the FDA, and drug sponsors all united in an effort to speed the development and review of critical new medicines.
A map for stepping up
In June, the FDA released official draft guidance outlining the key features and requirements of BTD. As expected, it is an “all hands on deck” approach that requires significant commitment from both the FDA and drug sponsors.
The new guidelines spell out what that commitment and collaboration means. Included are definitions of key terms like “serious condition” and “unmet need” – terms that have been used across all the FDA’s expedited programs for years but had not actually been specifically defined until now.
I was particularly impressed by the emphasis on efficient development overall, not just clinical trials and FDA review. In this, BTD is truly set apart from previous efforts. Speeding up processes like manufacturing requires a major commitment from drug sponsors and could have a significant impact on timelines.
While just about everyone expects that approvals under BTD will happen faster, we don’t exactly know how much faster. Some analysts are predicting the road from discovery to approval will be shortened by months or even years.
We should expect to get a rough sense from the aforementioned “Class of 2013,” and the difference will be even greater in the future as BTDs are granted to drugs at earlier stages of their development.
Learning as we go
We’ve made great progress in fleshing out the details of BTD, but there are still some major gaps we need to address (for a more detailed perspective, take a look at this article by my colleague Sandra Horning
Changing the Script on Clinical Trials
The classic three-phase model of clinical testing often lags behind the impressive early stage data supporting new investigational medicines. This is especially true for personalized therapies designed to work in very specific groups of patients. Accelerated approval was the main alternative, but science and technology have advanced substantially since that program was created 20 years ago. We need to rethink clinical trials to make BTD a meaningful reality. I believe innovative options like adaptive trial design, <http://www.gene.com/stories/can-a-new-pathway-get-medicines-to-patients-faster-">new endpoints, and additional forms of conditional approval are great places to start.
A diagnostic “buddy system”
Many new targeted medicines are designed to work in specific groups of patients, as defined by biomarkers. This means we often have to develop and validate tests – or companion diagnostics – alongside new medicines. Unfortunately, there’s no BTD equivalent for diagnostics yet. Bridging this gap is a topic of active discussion.
Even though BTD is still a work in progress, our commitment to patient safety will never change. Just as science is accelerating discovery, it's also improving our ability to assess safety at every stage of development. The use of biomarkers, for example, allows us to identify potential problems earlier than ever. These tools, combined with rigorous monitoring during clinical trials and after medicines are on the market, help ensure that speed does not compromise safety.
The FDA plays an important role in approving new medicines, but it’s just one of many global regulatory authorities. Expedited programs have previously been created in the European Union and elsewhere, and additional innovations should be considered in light of BTD.
The progress in defining and executing BTD so far has been very encouraging. Although challenges and controversies are an inevitable part of the process, these tensions often drive innovation forward – and that’s something we all can embrace.