Exelixis Shifts Focus as Kidney Cancer Triplet Fails to Improve Survival

Exelixis has abandoned plans to seek FDA approval for a combination of its drug Cabometyx with Bristol Myers Squibb's Opdivo and Yervoy in kidney cancer, following disappointing results from the phase 3 COSMIC-313 trial. The company is now redirecting its efforts towards other promising areas, including its next-generation tyrosine kinase inhibitor (TKI) and potential approvals in different indications.

COSMIC-313 Trial Results

The COSMIC-313 trial, which evaluated the triplet combination of Cabometyx, Opdivo, and Yervoy in previously untreated, intermediate- or poor-risk advanced renal cell carcinoma, failed to demonstrate an improvement in overall survival compared to the Opdivo-Yervoy doublet. Patients receiving the triplet lived a median of 41.9 months, versus 42 months for those on the doublet alone. The triplet was associated with a marginal 2% higher risk of death.

These results come after an earlier analysis had shown a 27% reduction in the risk of disease progression or death with the triplet combination. However, the magnitude of this progression-free survival benefit was deemed insufficient by the FDA, which requested more mature overall survival data before considering a filing.

Strategic Shift and Future Prospects

Despite the setback in kidney cancer, Exelixis remains optimistic about Cabometyx's potential in other areas:

1. Neuroendocrine Tumors (NETs): The company is awaiting an FDA decision for Cabometyx in NETs, expected by April 3, 2024. The recent cancellation of an advisory committee meeting is seen as a positive sign by industry analysts.

2. Next-Generation TKI: Exelixis is advancing zanzalintinib, its next-generation TKI, with phase 3 readouts in colorectal cancer and non-clear cell renal cell carcinoma expected in the second half of 2025.

3. Collaboration with Merck: A partnership has been established to test zanzalintinib with Merck's Welireg in two phase 3 kidney cancer studies, providing external validation for Exelixis' strategic positioning of the drug.

Financial Outlook and Market Position

Exelixis maintains an optimistic financial outlook, projecting Cabometyx revenue to reach $3 billion by 2030 and anticipating zanzalintinib could generate $5 billion in revenue by 2033. The company reported revenue of $2.17 billion for 2024, underscoring its current strong market position despite recent setbacks.

While the COSMIC-313 trial results represent a missed opportunity to expand market share in the competitive kidney cancer space, Exelixis continues to focus on diversifying its portfolio and exploring new indications for its existing and pipeline drugs.