Quavonlimab

Exelixis has projected Cabometyx revenue of $3 billion in 2030 and has said that its follow-on TKI, zanzalintinib, could reach $5 billion in 2033 revenue. Newly published detailed clinical trial data show why Exelixis abandoned a plan to seek an FDA approval for a combination of its Cabometyx and Bristol Myers Squibb’s Opdivo and Yervoy in kidney cancer.Adding Cabometyx to Opdivo and Yervoy failed to improve patients’ life expectancy in previously untreated, intermediate- or poor-risk advanced renal cell carcinoma, according to the final results from the phase 3 COSMIC-313 trial.Instead, the overall survival data slightly favored the doublet. Patients who received the Cabometyx-containing triplet lived a median 41.9 months, versus 42 months for Opdivo-Yervoy alone. The triplet was linked to a marginal 2% higher risk of death, according to data presented at the ASCO Genitourinary Cancers Symposium.When disclosing the overall survival miss in August, Exelixis’ chief medical officer, Amy Peterson, M.D., said the company did not plan to file the study with regulators for a possible label expansion.Several years ago, the Cabometyx-Opdivo-Yervoy combo showed it could reduce the risk of disease progression or death by 27% compared with Opdivo and Yervoy alone. The magnitude of that progression-free survival benefit, though statistically significant, was deemed weak, and the FDA requested to see more mature overall survival results to consider a filing.“We just didn’t see a risk-benefit profile going forward that was really going to raise the bar relative to the current combinations,” Exelixis’ commercial chief P.J. Haley said of the final COSMIC-313 readout on a conference call in August. It’s not the end of the world for Exelixis because the existing combination of Cabometyx and Opdivo has been the leading tyrosine kinase inhibitor (TKI)-plus-immunotherapy regimen in the competitive first-line kidney cancer field. However, the COSMIC-313 flop means the company missed an opportunity to take more market share.Meanwhile, for Cabometyx, Exelixis is focused on an upcoming FDA decision in neuroendocrine tumors (NETs) expected by April 3 this year. The FDA recently canceled an advisory committee meeting on that application, representing a positive sign for Exelixis, according to Citi analysts. Cabometyx has also posted some mixed data in metastatic castration-resistant prostate cancer. After the phase 3 CONTACT-02 trial missed its overall survival goal at the final analysis, Exelixis’ partner Ipsen called it quit on the indication in Europe.Exelixis itself previously appeared determined to pursue an U.S. approval. But, during the company’s fourth-quarter earnings call last week, CEO Michael Morrissey said the firm’s “singular focus right now from a regulatory point of view” is the NET indication and that it would circle back on prostate cancer once the expected NET approval is in the bag.Despite Cabometyx’s kidney cancer setback, Exelixis’ plan to grow beyond its bread and butter is taking shape. The company’s next-generation TKI, zanzalintinib, is approaching phase 3 readouts in colorectal cancer and non-clear cell renal cell carcinoma in the second half of 2025. In kidney cancer, Merck & Co. recently inked a collaboration with Exelixis to test zanzalintinib with the New Jersey pharma’s Welireg in two phase 3 studies.“We believe the collaboration with Merck provides a source of external validation to Exelixis’ strategic positioning of zanzalintinib as the next-generation version of Cabometyx,” William Blair analyst Andy Hsieh, Ph.D., said in a note when the deal was announced in October.As Hsieh noted, Merck already has the phase 3 LITESPARK-012 study evaluating the triplet of Welireg, Keytruda and Eisai-partnered Lenvima—as well as the co-formulated Keytruda and CTLA-4 inhibitor quavonlimab plus Lenvima—compared with the Keytruda-Lenvima doublet in first-line kidney cancer.“Given that Lenvima at the 20 mg dose had demonstrated tolerability challenges, we view Merck’s move to hedge its reliance on Lenvima as prudent,” Hsieh said.Exelixis has projected Cabometyx revenue will reach $3 billion in 2030 and that zanzalintinib could reach $5 billion in 2033 revenue. In 2024, the company generated $2.17 billion.