Lynparza can now be used in conjunction with Zytiga from Johnson & Johnson and a corticosteroid to treat individuals with mCRPC whose tumors include BRCA mutations. Lynparza’s usage in the mCRPC population is limited to roughly 10% of patients. The FDA’s decision comes after agency workers and an outside expert committee argued that the medicine only demonstrated a favorable risk-benefit ratio in that demographic.
The phase 3 PROpel study found that the combination reduced the probability of disease progression or mortality by 34% compared to Zytiga alone in newly diagnosed mCRPC patients independent of mutation status. The FDA recognized significant design flaws in the experiment in its briefing materials before the meeting. The FDA specifically claimed that the study did not enroll patients in distinct cohorts based on biomarker status and did not provide subgroup analysis based on mutations.
The FDA discovered that 11% of trial participants with BRCA mutations appeared to benefit from Lynparza. The medication increased progression-free survival by 76% and reduced the chance of mortality by 70% in those individuals. The firms attempted to demonstrate that the outcomes in the larger non-BRCA group were clinically significant, but the FDA stated that the effectiveness was uncertain.
The advisory committee specialists also raised concerns about uncertainties among the non-BRCA population, prompting the decision for restricted approval.
According to EVP of oncology, Dave Fredrickson, the clearance underscores the importance of BRCA testing at metastatic diagnosis. In Europe, the combination is authorized for the full mCRPC population. It is also used to treat individuals with homologous recombination repair gene-mutated mCRPC who have progressed after earlier therapy with certain other medications in the United States.
AZ and Merck are working to broaden the drug’s availability. Lynparza recently won a study on patients with newly diagnosed, advanced ovarian cancer who did not have BRCA mutations when combined with AZ’s Imfinzi with chemotherapy and bevacizumab. In May, the Lynparza and Imfinzi combination was also found to be effective in endometrial cancer.
As a result, analysts are decreasing their sales projections. Berens previously projected up to $4.2 billion in possible peak sales for Lynparza in prostate cancer in the United States and Europe. Following the conversation, he reduced his prediction to $1.2 billion. Berens predicted $680 million in annual sales potential in the United States.
The FDA’s decision might have ramifications for Pfizer, which published good Phase 3 findings for its PARP inhibitor Talzenna in front-line prostate cancer. Pfizer stated that it noticed a benefit independent of the genetics of the individuals. However, it was too soon to know if Talzenna helped patients live longer lives.