Clovis' Rubraca wins prostate cancer approval, but data from rival Lynparza dampen commercial expectations
While AstraZeneca and Merck’s market-leading Lynparza seemingly pipped Clovis Oncology’s rival Rubraca in helping prostate cancer patients, Rubraca has, as expected, made it across the finish line first.
On Friday, the FDA approved Rubraca in patients with BRCA mutation-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated previously with androgen receptor-directed therapy as well as chemotherapy. The approval marks the first ever for a PARP inhibitor in the prostate cancer setting.
The approval was based on a single-arm TRITON2 study, with a 44% confirmed objective response rate in 62 second-line patients. A late-stage study evaluating the impact of Rubraca on overall survival in prostate cancer patients is ongoing.
“While Clovis has an ongoing randomized trial with OS as a key secondary endpoint, TRITON3, we would not expect this benefit to be demonstrated in time to have a significant commercial impact, as Lynparza may have already advanced to the frontline, based on the Phase 3 PROpel trial with initial data expected in 2021,” SVB Leerink analyst Andrew Berens wrote in a note in late April.
In April, Lynparza eclipsed the anti-androgen therapies Pfizer and Astellas’ Xtandi and Johnson & Johnson’s Zytiga by helping men with metastatic, castration-resistant prostate cancer with BRCA or ATM gene mutations live longer. Previously unveiled data also showed the PARP inhibitor superseded the impact of the androgen therapies at reducing the risk of disease progression or death — by a sharp 66%.
“While Rubraca requires prior treatment with both an androgen-receptor and taxane therapy, Lynparza’s registrational PROfound study only requires prior treatment with an androgen-receptor treatment…as such, while Rubraca is approved as a 3L therapy, Lynparza could obtain approval as a 2L + agent,” Berens wrote in a note on Monday. “Furthermore, AZN’s PROpel study, which would expand the Lynparza label into 1L mCRPC treatment in combination with abiraterone, is expected to announce data in 2021, potentially moving Lynparza to the frontline. In comparison, CLVS’ TRITON3 study investigating Rubraca versus physician’s choice of androgen-receptor or chemotherapy in 1L mCRPC will not read out data until 2022.”
Berens has adjusted his peak Rubraca prostate revenue to $130 million globally.
Akin to Lynparza, Clovis’ Rubraca and GSK’s Zejula are poly (ADP-ribose) polymerase (PARP) inhibitors. PARP is a protein used by damaged cells to initiate repair, and by thwarting it, the class of drugs is engineered to prevent cancer cells from repairing themselves, thereby catalyzing their destruction.
While drug developers have primarily relied on BRCA mutations to identify patients who can benefit from this family of therapies, scientists have suggested that defects in other genes involved in DNA repair — which render cells cancerous — could be prime targets too.