ASCO: Merck KGaA, Pfizer's Bavencio combo fails survival goal in kidney cancer

Five years after gaining FDA approval for newly diagnosed advanced kidney cancer, Merck KGaA and Pfizer's Bavencio-Inlyta combination has failed to meet its overall survival (OS) endpoint in a phase 3 trial. Despite showing a 14% reduction in the risk of death compared to Pfizer’s Sutent in patients with PD-L1 expression, the results did not reach statistical significance after a median follow-up of over six years. This outcome means the study has missed one of its two primary endpoints, with a smaller 12% risk reduction observed in the overall trial population.

The trial results were released in an abstract and will be detailed at the American Society of Clinical Oncology 2024 annual meeting. Although the FDA approval of Bavencio remains intact, the missed OS endpoint is a setback for its standing against Merck & Co. and Bristol Myers Squibb's PD-1/TKI combinations.

Merck KGaA’s EMD Serono biopharma division noted that longer follow-ups tend to be unfavorable for OS outcomes in immunotherapy-based regimens for first-line kidney cancer due to external factors influencing the analyses. For example, Bristol Myers Squibb's Opdivo and Exelixis’ Cabometyx combination initially showed a 30% risk reduction compared to Sutent, which decreased to 23% after a longer follow-up. Similarly, Merck's Keytruda, in combination with Inlyta, showed a 47% death risk reduction against Sutent after a short follow-up, which later decreased to 32%.

Among patients with a favorable risk profile, Bavencio and Inlyta demonstrated a 27% reduction in the risk of death, the largest benefit in this subgroup compared to existing therapies. The combination also had a low discontinuation rate, with only 4.8% of patients stopping both drugs due to adverse events, compared to 9.3% for Sutent.

A spokesperson for Merck KGaA emphasized the clinical and real-world benefits of the Bavencio-Inlyta combination, particularly for patients with a favorable-risk profile and older patients where maintaining quality of life is crucial. Despite these points, the regimen is generally seen as less effective than other PD-1/TKI combinations, such as Keytruda's pairing with Lenvima.

Given the competitive landscape, Merck KGaA has maintained a limited focus on kidney cancer, instead prioritizing Bavencio in bladder cancer treatment. Bavencio is approved for first-line maintenance in advanced bladder cancer, the drug’s largest indication in the U.S. However, it now faces competition from Keytruda combined with Pfizer and Astellas’ Padcev, an antibody-drug conjugate that recently entered the first-line bladder cancer treatment market.

Peter Guenter, head of Merck KGaA’s pharma business, remarked that while Keytruda-Padcev hasn’t significantly impacted Bavencio sales yet, a decline in platinum-based chemotherapy use suggests Bavencio might see greater competition starting in the second quarter of 2024. Despite this, Bavencio's sales grew by 14% year-over-year in the first quarter to 186 million euros, with only about 30% of sales coming from the U.S. Merck KGaA expects continued growth for Bavencio in 2024.

Previously, Merck KGaA shared Bavencio rights with Pfizer until Pfizer returned its stake to gain antitrust clearance for its $43 billion acquisition of Seagen, which co-developed Padcev.