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

Exelixis, a prominent biotechnology company, faced a significant setback as its shares plummeted by over 10% following the release of data 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 failed to meet investor expectations.

Trial Results and Market Reaction

The STELLAR-303 trial, involving 901 patients with advanced colorectal cancer, compared the efficacy of zanzalintinib plus Tecentriq against Stivarga, a commonly used treatment. While the study met its primary endpoint of improving overall survival, the margin of benefit was narrow. Median overall survival in the combination arm was 10.9 months, compared to 9.4 months in the Stivarga arm.

Despite Exelixis' assertion that the survival benefit was consistent across various patient subgroups, including those with RAS mutations and prior anti-VEGF therapy exposure, the market response was decidedly negative. Analysts, including Yaron Werber from TD Cowen, noted that key oncologists had hoped for a more substantial survival benefit and improved safety profile.

Safety Concerns and Competitive Landscape

The trial data revealed significant safety concerns, with 59% of patients in the zanzalintinib arm experiencing severe or life-threatening adverse events, compared to 37% in the Stivarga group. Common side effects included hypertension, fatigue, diarrhea, and proteinuria. Moreover, six treatment-related deaths were reported across both arms of the study.

Comparatively, the efficacy of zanzalintinib plus Tecentriq was found to be similar to the current standard of care for third-line metastatic colorectal cancer, a combination of Avastin and Lonsurf. This equivalence in efficacy, coupled with the safety profile, has led analysts to predict that the new combination may be relegated to later lines of therapy.

Regulatory Plans and Industry Implications

Despite the lukewarm reception, Exelixis remains committed to advancing zanzalintinib. Dana Aftab, head of research and development at Exelixis, stated that the company plans to submit a regulatory application to the Food and Drug Administration by the end of the year. However, the underwhelming results may impact the drug's potential market position and commercial prospects.

The outcome of the STELLAR-303 trial underscores the challenges in developing effective treatments for advanced colorectal cancer, a notoriously difficult-to-treat malignancy. As the pharmaceutical industry continues to invest heavily in oncology research, this setback for Exelixis serves as a reminder of the high stakes and unpredictable nature of cancer drug development.