What are the comparative advantages of “breakthrough,” “fast track” and other FDA designations? Is the agency becoming more amenable to approving drugs based on small phase 2 studies? And how will these and other FDA policies change under new commissioner Scott Gottlieb?
Those were some of the questions addressed by three biotech veterans who spoke at the second annual FierceBiotech Drug Development Forum in Boston this week. All brought different perspectives to the issue of how companies can chart the clearest path to drug approval, but they all agreed on one point: The agency was taking positive steps towards the goal of facilitating faster approvals prior to Gottlieb’s appointment, and if anyone’s qualified to build upon those initiatives, it’s him.
Gottlieb is “one of the better choices because he actually worked at the FDA before. He understands how it really works,” said Martha Carter, chief regulatory officer of Albireo Pharma, which is developing three drugs to treat rare liver and gastrointestinal diseases. “He has sensibility about what the industry is trying to do, and he isn’t coming in to systematically dismantle it.”
The panelists agreed that the proliferation of special designations by the FDA has only helped the drug-development process. Maria Fardis, CEO of Iovance Biotherapeutics (formerly Lion Biotechnologies) advised audience members that one of the most important strategy decisions for early-stage biotechs is to decide whether to apply for breakthrough designation or fast track status.
“Breakthrough will give you more in terms of the exchanges you can have with FDA,” Fardis said. That can be “helpful in ensuring the program gets the support it needs,” she said. Fast track gives you “a subset of those benefits,” plus the potential to do a rolling submission, she said. Her advice: If you have robust clinical data in an orphan indication, consider breakthrough designation. Iovance is working on cell therapies for oncology indications, and in August, the company was granted fast track designation for LN-144, a melanoma treatment that uses tumor-infiltrating lymphocyte technology.
A new twist on breakthrough status is the Regenerative Medicine Advanced Therapy (RMAT) designation, Fardis said. RMAT, instituted in March of this year, is specifically aimed at companies working on cell therapies and tissue engineering.
“There’s not a lot of information,” she said, “but it is something that cell therapy companies should consider.”
Charles Theuer, CEO of Tracon Pharmaceuticals, advised conference attendees not to get hung up in densely worded FDA guidance documents that may seem designed to dissuade companies from pursuing “aggressive” research protocols. “The FDA really wants to work with companies that address unmet needs, to develop therapeutics that have a meaningful impact for patients. If you’re developing an orphan indication you can expect a positive interaction with the agency,” Theuer said.
The guidances ”may not reflect the current thinking of the FDA, especially the FDA under the new commissioner,“ he added. “If you propose aggressive designs to get drugs approved in unmet needs, the FDA may be very open to those types of interactions.”
For example, Tracon is developing a drug for angiosarcoma, a rare cancer for which there are no FDA-approved drugs. The company’s trial has an adaptive design, meaning the protocol can change based on how patients are responding. “If you looked at the adaptive design guidelines from years ago, you’d be very hesitant to propose it at all. But in this day and age, the thinking of the agency has evolved,” Theuer said. So you can propose adjusting the sample sizes based on interim data analyses, he said, or enrolling different subsets of patients after a trial is already underway.
Theuer predicted that the FDA will greenlight an increasing number of “seamless” research programs, such as combination phase 1/2 trials. He advised biotech executives to explore such trials as a way to cut down on development costs and potentially shorten the approval timeline.
All in all, the panelists concluded, now is as good a time as ever to be bringing innovative products to the FDA. Gottlieb, said Carter, is embracing a range of new ideas, from using computer modeling tools to improve preclinical research, to incorporating real-world evidence into clinical trials. “It makes perfect sense,” she said. “With the power of computers now we can do a lot of modeling. It’s super important for us to understand how we can mine the data.”