citing recent data showing an increased risk for death with the agents versus chemotherapy.
These restrictions could mean bankruptcy for one company.
Earlier this year, several companiestheir respective PARP inhibitors for heavily pretreated patients with ovarian cancer in later-line indications.
Now, the FDA has asked GlaxoSmithKline and Clovis Oncology to restrict the second-line indications for their PARP inhibitors –(Zejula) for GSK and (Rubraca) for Clovis.
The FDA’s requests are based on recent data showing an increased risk for death with the PARP inhibitors versus chemotherapy.
On Nov. 11,that, at the FDA’s request, it will limit the second-line maintenance indication for its PARP inhibitor niraparib to patients with deleterious or suspected deleterious germline BRCA mutations.
The prescribing change was based on an FDA review of the final overall survival analysis ofwhich served as the basis for the approval of the second-line maintenance indication. The final overall survival data showed a hazard ratio of 1.06 (95% confidence interval, 0.81-1.37) in the cohort without germline BRCA mutations.
The company noted, however, that its first-line indication remains unchanged.
The FDA has also asked Clovis Oncology to restrict its PARP inhibitor rucaparib in the second-line maintenance therapy setting, according to a Nov. 14 U.S.from the company. Rucaparib is currently not approved to treat ovarian cancer in the first-line setting.
According to the filing, the FDA met with Clovis Oncology to discuss the overall survival data from the ARIEL3 clinical trial, which formed the basis for the drug’s approval in the United Statesfor adult patients with recurrent epithelial ovarian, fallopian tube, or primary who had a complete or partial response to platinum-based chemotherapy.
In September 2022, Clovis Oncology submitted the final overall survival data from the ARIEL3 trial to FDA., among all populations analyzed, the confidence intervals for all hazard ratios crossed 1, “indicating no difference between the treatment arms.”
Based on the overall survival data, the FDA requested that Clovis “voluntarily revise the label to limit the indication of Rubraca in this second-line maintenance treatment” to only patients with BRCA mutations.
Clovis said it is “currently evaluating FDA’s request.” If an agreement can’t be reached, the FDA said it would convene an advisory committee to review the matter.
However, further restricting the indication for rucaparib could put the company’s future in jeopardy. In an, Clovis Oncology foreshadowed a “potential bankruptcy filing in the very near term” as “increasingly probable.”
The company explained that, because “a substantial portion” of the drug’s revenue is attributable to its second-line indication, limiting that indication “could result in a significant impact on our revenue.”
The report continued: “Based on our current cash and cash equivalents, together with current estimates for revenues to be generated by sales of Rubraca, we will not have sufficient liquidity to maintain our operations beyond January 2023.”
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