The FDA’s New Breakthrough Therapy Designation
The FDA recently added a new designation, ‘Breakthrough Therapy’, to its roster of pharmaceutical regulatory terminology in order to ensure that truly innovative compounds get to the patients who need them most as soon as possible. This new designation was enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA). The Breakthrough Therapy designation will provide companies with the opportunity for a streamlined developmental process, which could greatly shorten the development timeline.
How the Breakthrough Therapy Request Process Works
A company can request the designation from the FDA at any time after the original IND submission, but is under no obligation to publicly announce the request. Once the FDA grants the compound the Breakthrough Therapy designation, the process for approval becomes abbreviated. The FDA representatives effectively form an advisory panel with the company, in order to determine the most efficient trial designs. The review time will also be shortened due to the rolling NDA / BLA submission.
Oncology Likely to Benefit Most
While the language of the bill does not specifically refer to oncology as a primary source of Breakthrough therapies, it is likely that a majority of these designations will apply to oncology compounds. Other diseases that have already received Breakthrough Therapy status include the rare genetic disease epidermolysis bullosa, hepatitis C and cystic fibrosis.
Flexible Approval Standards
These new breakthrough therapies must show early clinical evidence of a substantial improvement over existing therapies for serious or life-threatening diseases. The bill purposefully left the approval standards vague, so that a judgment call can be made by the reviewers at the FDA. There is no efficacy bar set; however officials warn that if a company wonders if their drug is in a grey area, it is unlikely to be a true breakthrough.
Rigorous Data Requirements Remain
The data requirements for Breakthrough Therapies will be as rigorous as other submissions, but other faster trial designs may be possible for these compounds. The options could include a phase Ib expansion or single-arm pivotal trial for diseases states where there is no standard of care. A phase IIb randomized controlled trial with a modest-sized population might also be an option for some of these compounds where substantial efficacy benefit is seen over the standard of care. Both these options and others could lead to either full or accelerated approval.
50% Breakthrough Therapy Approval Rate So Far
Over a dozen companies have already sought the Breakthrough Therapy designation, with approvals being granted to approximately half. One of the compounds recently granted Breakthrough Therapy status is Pfizer’s palbociclib, an oral inhibitor of cyclin-dependent kinases (CDK) 4 and 6. The designation was granted based on preliminary data from their phase II trial in first-line post-menopausal patients with ER+, HER2- locally advanced or metastatic breast cancer. Interim data presented at the 2012 San Antonio Breast Cancer Symposium showed that women treated with the combination of palbociclib plus letrozole achieved a statistically significant improvement in median progression free survival (PFS) compared to women who received letrozole alone (26.1 months and 7.5 months, respectively).
Official FDA Guidance Set for July 2013
The official master guidance will be released by the FDA in July of 2013; however it is clear that this new designation will provide a significant benefit to qualifying extraordinary therapies.
Pharmaceutical Industry Hurdles
What remains unclear at this time is how the already underfunded FDA will manage to provide even more time and attention to these compounds and how much the designation will actually streamline the regulatory pathway.