Building on an FDA nod last year for Lynparza in some previously treated patients with prostate cancer, AstraZeneca and Merck are now trumpeting first-in-class positive data from a clinical trial that could open a broader market for the PARP inhibitor.
Lynparza plus Johnson & Johnson’s Zytiga prolonged the time to tumor progression or death over Zytiga alone in men with previously untreated metastatic, castration-resistant prostate cancer (CRPC) regardless of their homologous recombination repair (HRR) mutation status, AZ and Merck said Friday. All patients also received corticosteroids.
The positive readout, which came from a planned interim analysis of the phase 3 PROpel trial, has made Lynparza the first PARP inhibitor to show clinical benefit in this first-line setting. Even though the data are immature, the companies plan to take them to regulators, Susan Galbraith, AZ’s oncology R&D head, said in a statement.
It's no surprise the companies are in a hurry to open a dialog with regulators. All other marketed PARP meds—including two by entrenched prostate cancer players—are targeting front-line metastatic CRPC.
Thanks to an FDA green light last May, Lynparza is already cleared for the treatment of HRR-mutated metastatic CRPC following prior treatment with Pfizer and Astellas’ Xtandi or Zytiga. Another accelerated approval the FDA handed to Clovis Oncology last May gave rival PARP inhibitor Rubraca a path into the third-line treatment of BRCA-mutant, metastatic CRPC. BRCA mutations are a type of HRR deficiency.
But the race to conquer the first-line market is heating up among PARP players. J&J’s Janssen unit—which holds the rights to Zejula in prostate cancer through a 2016 licensing deal with its inventor, Tesaro—is pairing the PARP inhibitor with Zytiga plus prednisone in patients who didn’t get any prior treatment in the phase 3 MAGNITUDE trial, which covers all comers with or without HRR gene alterations.
As for Clovis' Rubraca, investigators at the National Cancer Institute recently launched a phase 3 trial dubbed CASPAR to test whether combining the drug with Xtandi outperforms Xtandi alone in the front-line treatment of metastatic CRPC.
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What’s more, Pfizer’s Talzenna, which is only approved to treat BRCA-mutated breast cancer, is now in the phase 3 TALAPRO-2 trial in prostate cancer. Pfizer is collaborating with Astellas to test Talzenna in combination with Xtandi.
Lynparza is leading the PARP inhibitor field, with sales of $1.13 billion in the first six months of 2021, marking 15% year-over-year growth at constant currencies. With the latest prostate cancer win and recent positive data for use in patients with high-risk early breast cancer after surgery, the drug seems to be on a strong growth path. And Zytiga brought in $1.2 billion in worldwide sales in the first half of the year, despite generic erosion and competition from newer meds.