Teva Pharmaceutical Industries Ltd.
and OncoGenex Pharmaceuticals, Inc.
today announced results from the Phase III SYNERGY trial, a randomized, open-label, two-arm study comparing the combination of custirsen and standard first-line docetaxel/prednisone therapy to docetaxel/prednisone alone in men with metastatic castrate-resistant prostate cancer (CRPC).
Top-line survival results indicate the addition of custirsen to standard first-line docetaxel/prednisone therapy did not meet the primary endpoint of a statistically significant improvement in overall survival (OS) in men with metastatic CRPC, compared to docetaxel/prednisone alone (median survival 23.4 months vs 22.2 months, respectively; hazard ratio 0.93 and one-sided p-value 0.207).
“We are disappointed with these results. Addressing treatment resistance is critical in the fight against cancer. We are working with OncoGenex to more fully understand these data,” said Michael Hayden, MD, president of global R&D and chief scientific officer at Teva Pharmaceutical Industries Ltd.
The adverse events (AEs) observed for custirsen were similar to its known AE profile.
Full efficacy and safety data from SYNERGY will be submitted for presentation at an upcoming scientific conference.
Custirsen is an experimental drug that is designed to block the production of the protein clusterin, which may play a fundamental role in cancer cell survival and treatment resistance. Clusterin is upregulated in tumor cells in response to treatment interventions such as chemotherapy, hormone ablation and radiation therapy and has been found to be overexpressed in a number of cancers, including prostate, lung, breast and bladder. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration. By inhibiting clusterin, custirsen is designed to alter tumor dynamics, slowing tumor growth and resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.
As part of Phase 1 and Phase 2 clinical trials, custirsen was administered to 294 patients with various types of cancer. The majority of adverse events were mild. The most common adverse events associated with custirsen consisted of flu-like symptoms. The most common serious adverse events (SAE) associated with custirsen were febrile neutropenia, fever, pleural effusion, and dyspnea. Each SAE event was observed in approximately 2%-4% of patients.