The FDA has decided it no longer needs input from external experts on an ovarian cancer indication for GSK’s Zejula.
The oncologic drugs advisory committee was supposed to meet Nov. 22 to weigh in on Zejula’s existing approval as a second-line maintenance therapy for patients with recurrent ovarian cancer who’ve responded to chemotherapy. But in a recent update, the FDA said the meeting is “no longer needed.”
But that doesn’t mean the axe dangling over that Zejula indication has been removed. “GSK is in ongoing discussions with the FDA and will provide further information as discussions progress,” a GSK spokesperson told Fierce Pharma.
The FDA started scrutinizing Zejula’s second-line maintenance use after long-term patient survival data arrived from the phase 3 Nova trial. The drug previously won its approval based on data from the same study showing it could stall tumor progression or death when compared to placebo.
But when it comes to life extension, the Nova trial found that Zejula only cut the risk of death by 7% in germline BRCA-mutant tumors, which typically respond well to PARP inhibitors like Zejula. After adjusting for follow-on PARP inhibitor use, Zejula cut the risk of death by 34% in this subgroup, according to data presented at last year’s Society of Gynecologic Oncology annual meeting.
In tumors without BRCA mutations, Zejula instead showed a 10% increase in death risk as patients who took the GSK drug lived a median 31.1 months, versus 36.5 months for the control group. Even after adjusting for subsequent use of PARP inhibitors, investigators observed no difference in survival for this cohort.
By contrast, the use of Zejula—an active drug—markedly increased the incidence of side effects compared with placebo.
The latest scrutiny also comes as the use of PARP inhibitors in late-line ovarian cancer has been challenged. After clinical trials showed ovarian cancer patients receiving a PARP inhibitor appeared to live shorter than those on chemotherapy did in late-line treatment, the FDA has questioned whether the harm done by increased toxicity might be greater than this class of drugs’ tumor-killing effect in that setting. Zejula, AstraZeneca and Merck’s Lynparza and Clovis Oncology’s Rubraca have since pulled their late-line ovarian cancer nods.
If the FDA is indeed not done yet with Zejula’s second-line maintenance nod, several scenarios could eventually play out. The FDA could pressure GSK to withdraw the indication altogether, just as it did with the third-line approval. Or, the agency could let the approval stay intact. But perhaps the most likely outcome is that the FDA could limit the approval to BRCA-mutant disease instead of an all-comers label.
Meanwhile, both Zejula and Lynparza have recently moved earlier to the first-line maintenance setting in ovarian cancer. Zejula’s phase 3 Prima trial has once again showed a benefit in preventing disease progression or death, but data on overall survival weren’t mature as of GSK’s last communication in September.