GSK Pulls Blenrep Accelerated Approval at FDA’s Request
GSK says that at FDA’s request it is withdrawing the accelerated approval for Blenrep (belantamab mafodotin-blmf) due to the therapy’s poor showing in progression-free survival (PFS) in a Phase 3 confirmatory study. The monotherapy treatment was granted accelerated approval in 2020 for adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.
The decision to withdraw the therapy comes two weeks after the company announced (see story) results from a Phase 3 trial (DREAMM-3) where Blenrep versus pomalidomide in combination with low dose dexamethasone (PomDex) was studied in an open-label, randomized head-to-head superiority trial design. While Blenrep did not meet the PFS endpoint, the company did note median PFS was longer in patients treated with the therapy versus PomDex (11.2 months vs 7 months). “At the time of the primary analysis, the OS [overall survival] data had only achieved 37.5% overall maturity,” it says adding that the median OS was 21.2 and 21.1 months for belantamab mafodotin and PomDex, respectively.
The seemingly quick withdrawal decision could signal greater FDA scrutiny of the accelerated approval program that unexpectedly was thrown under the microscope after Biogen’s controversial accelerated approval of Aduhelm (aducanumab) for treating Alzheimer’s patients and the company’s estimate that it will take nine years to do the follow-up confirmatory study. Earlier this month, FDA began raising the bar for sponsors seeking accelerated approval by requesting that they be well underway with their Phase 3 confirmatory trial and ideally fully enrolled. This requirement by the agency was laid out for ADC Therapeutics during a meeting to discuss a potential accelerated approval BLA filing for Cami (camidanlumab tesirine) and its use in relapsed or refractory Hodgkin lymphoma.
Requiring sponsors to have their confirmatory trials well underway at the time of initial submission was a goal FDA supported as an accelerated approval reform provision during the recent user fee negotiations. It and other reform provisions were abandoned by lawmakers when they ran out of time as the user fee programs had to be reauthorized by 9/30 (see earlier story).
Last month, FDA commissioner Robert Califf revived his previous support for revamping the drug accelerated approval program. Delivering remarks at the 2022 National Organization for Rare Disorders Breakthrough Summit in Washington, DC, Califf said improvements in the accelerated approval program are needed as soon as possible. Califf acknowledged then that the program’s biggest fault is probably companies being “too focused on just the acceleration and not enough on the evidence that’s needed to fill in that gap between when approval occurs and when you need the definitive evidence that the treatment fulfills its promise.” He said he supported user fee provisions, such as requiring sponsors to have a confirmatory trial underway at the time of approval, and additional authorities to more efficiently deal with companies who don’t fulfill their confirmatory evidence requirements.
Several of these potential accelerated approval reform provisions could come up again next month when a temporary funding bill must be renegotiated by Congress, according to FDA watchers