The US Food and Drug Administration (FDA) plans to further restrict the use of certain PARP inhibitors in ovarian cancer patients, citing recent data showing an increased risk of death from the drugs compared to chemotherapy.
These restrictions could mean bankruptcy for one company.
Earlier this year, several companies voluntarily withdrew their PARP inhibitors for heavily pretreated ovarian cancer patients in later indications.
Now the FDA has asked GlaxoSmithKline (GSK) and Clovis Oncology to limit second-line indications for their PARP inhibitors – niraparib (Zejula) for GSK and rucaparib (Rubraca) for Clovis.
The FDA’s requests are based on recent data showing an increased risk of death with PARP inhibitors compared to chemotherapy.
On November 11, GSK announced that, at the request of the FDA, it will limit the second-line maintenance indication for its PARP inhibitor niraparib to patients with malignant or suspected malignant germline. BRCA mutations.
The prescription change was based on the FDA’s review of the final overall survival analysis of the phase 3 NOVA study, which was the basis for approval of the second-line maintenance indication. Final overall survival data showed a hazard ratio (HR) of 1.06 (95% CI, 0.81 – 1.37) in the germline group BRCA mutations.
However, the company noted that its initial indication remains unchanged.
The FDA has also asked Clovis Oncology to limit its PARP inhibitor rucaparib to second-line maintenance therapy, according to a November 14 US Securities and Exchange Commission filing by the company. Rucaparib is not currently approved for first-line treatment of ovarian cancer.
According to the filing, the FDA met with Clovis Oncology to discuss overall survival data from the ARIEL3 clinical trial, which was the basis for the drug’s approval in the United States as second-line maintenance for adult patients with recurrent ovarian, fallopian tube, or ovarian cancer. , or primary peritoneal cancer that had a complete or partial response to platinum-based chemotherapy.
In September 2022, Clovis Oncology submitted final overall survival data from the ARIEL3 trial to the FDA. According to the company, among all populations analyzed, the confidence intervals of all hazard ratios exceeded 1, “indicating no difference between the treatment groups.”
Based on the overall survival data, the FDA requested that Clovis “voluntarily revise the label to limit the indication of Rubraca in this second maintenance regimen” to only patients with BRCA mutations.
Clovis said it is “currently evaluating the FDA’s request.” If no agreement is reached, the FDA said it will convene an advisory panel to review the issue.
However, further limiting the indication for rucaparib could put the company’s future at risk. In an earlier report, Clovis Oncology predicted a “potential bankruptcy filing in the very near term” as “more likely.”
The company explained that because a “significant portion” of the drug’s revenue is attributable to its second-line indication, limiting that indication “could have a significant impact on our revenue.”
The report continued: “Based on our current cash and cash equivalents, along with our current estimates of revenue generated from the sale of Rubraca, we will not have sufficient liquidity to sustain our operations beyond January 2023.”
Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, who writes for Medscape, MDedge and other related sites. She currently covers oncology, but has also written on a variety of other medical and health care topics. She can be reached at email@example.com or on Twitter, @SW_MedReporter
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