Exelixis Shares Dip as Colorectal Cancer Trial Results Fall Short of Expectations

Exelixis, a prominent biotechnology company, faced a setback on Monday as its shares dropped more than 10% following the release of results from a pivotal clinical trial. The STELLAR-303 study, which tested the experimental drug zanzalintinib in combination with Tecentriq for metastatic colorectal cancer, yielded results that left some investors and analysts underwhelmed.

Trial Results and Market Reaction

The STELLAR-303 trial, involving 901 patients with metastatic colorectal cancer who had progressed after previous treatments, compared the efficacy of zanzalintinib plus Tecentriq against Stivarga, a commonly used medication for advanced colorectal cancer. While the study met its primary endpoint of improving overall survival, the margin of benefit was modest:

• Median overall survival in the combination arm: 10.9 months
• Median overall survival in the Stivarga arm: 9.4 months

This 1.5-month survival advantage, observed after a median follow-up of 18 months, was consistent across various patient subgroups, including those with RAS mutations and prior anti-VEGF therapy exposure. However, the results failed to significantly outperform the current standard of care, leading to a negative market reaction.

Safety Concerns and Comparison to Existing Treatments

The trial also raised some safety concerns:

• Severe or life-threatening adverse events: 59% in the zanzalintinib arm vs. 37% in the Stivarga arm
• Most common side effects: hypertension, fatigue, diarrhea, and proteinuria
• Treatment-related deaths: 6 in total (2 for zanzalintinib, 2 for Tecentriq, 1 for the combination, and 1 for Stivarga)

Yaron Werber, an analyst at TD Cowen, noted that the efficacy of the zanzalintinib-Tecentriq combination was comparable to the current standard of care (Avastin plus Lonsurf) for third-line metastatic colorectal cancer treatment. This similarity in effectiveness, coupled with the higher rate of adverse events, may limit the potential market positioning of Exelixis's new treatment.

Future Prospects and Industry Implications

Despite the market's lukewarm reception, Exelixis remains committed to advancing zanzalintinib. Dana Aftab, head of research and development at Exelixis, stated that the company plans to submit an approval application to the FDA before the end of the year. However, industry experts suggest that the combination therapy may be relegated to later lines of colorectal cancer treatment due to its modest efficacy and safety profile.

The results of the STELLAR-303 trial, published in The Lancet and presented at the European Society for Medical Oncology's annual meeting, highlight the ongoing challenges in developing breakthrough treatments for advanced colorectal cancer. As the pharmaceutical industry continues to seek more effective therapies, this setback for Exelixis underscores the high bar set for new cancer treatments in terms of both efficacy and safety.