Exelixis Shifts Focus to Next-Gen Cancer Drug as Cabometyx Falls Short in Key Trials

Exelixis, a prominent player in the oncology drug development arena, is pivoting its strategy towards its next-generation tyrosine kinase inhibitor, zanzalintinib, following disappointing results from recent clinical trials of its flagship drug, Cabometyx. This shift comes as the pharmaceutical industry continues to seek more effective treatments for various cancer types.

Cabometyx Underwhelms in Late-Stage Trials

Exelixis's Cabometyx (cabozantinib) has faced setbacks in two major Phase III trials. The COSMIC-313 trial, investigating Cabometyx in combination with Bristol Myers Squibb's Opdivo and Yervoy for advanced renal cell carcinoma (RCC), failed to demonstrate a significant improvement in overall survival (OS). Patients receiving the Cabometyx combination showed a median OS of 41.9 months, compared to 42 months for those on the Opdivo-Yervoy doublet alone.

Similarly, the CONTACT-02 study in metastatic castration-resistant prostate cancer, which combined Cabometyx with Roche's Tecentriq, yielded only a "numerical but not statistically significant improvement" in survival outcomes.

These results have led Exelixis to abandon plans for seeking label extensions based on these studies. However, the company did note a positive development for Cabometyx in neuroendocrine tumors, with the FDA currently reviewing its application for this indication, targeting an action date of April 3.

Zanzalintinib: Exelixis's Next Frontier

In light of Cabometyx's recent performance, Exelixis is increasingly focusing on zanzalintinib, its next-generation tyrosine kinase inhibitor. CEO Michael Morissey emphasized this shift in the company's recent fourth-quarter business report, stating that "we expect zanzalintinib to take center stage in 2025 as our next franchise opportunity."

Zanzalintinib is currently being evaluated for multiple cancer types, including colorectal cancer, renal cell carcinoma, and head-and-neck cancer. The drug's potential is significant, with analysts at William Blair projecting that it could reach $5 billion in net U.S. sales by 2033.

Several key readouts for zanzalintinib are anticipated in the second half of 2025, which could provide crucial insights into the drug's efficacy and potential market impact. These results will be closely watched by industry observers and investors alike, as they could shape Exelixis's future in the competitive oncology market.