FDA delays Exelixis' zanzalintinib decision to March 2027

The U.S. Food and Drug Administration has delayed its approval decision for Exelixis’ oral kinase inhibitor zanzalintinib. The drug is being reviewed in combination with Roche’s Tecentriq for treating patients with metastatic colorectal cancer (mCRC).

Exelixis disclosed the delay in a Securities and Exchange Commission filing. The agency requested an extension to review updated safety and efficacy data from the company. This pushes the expected decision date to March 2027, from a previous deadline of December 3, 2026.

The regulatory submission faced uncertainty earlier this year. In June, zanzalintinib failed to meet one of two primary endpoints in a phase 3 study. It did not show a statistically significant improvement in overall survival for a specific subpopulation of mCRC patients with liver metastases.

Trial results and analyst views

Despite that setback, the trial successfully met its other primary endpoint. It demonstrated a significant overall survival benefit for all study participants, regardless of liver metastases status. Analysts from Leerink Partners and William Blair argued this broader success would likely still lead to FDA approval for third-line mCRC treatment.

The drug had shown promise last year. In a separate phase 3 trial, zanzalintinib demonstrated significantly longer overall survival compared to Bayer’s existing gastrointestinal cancer drug, Stivarga. This positioned it as a potential candidate for combination therapy with Roche's anti-PD-L1 drug, Tecentriq.

Analysts at William Blair told investors they believe the risk of FDA rejection for the zanzalintinib-Tecentriq combination remains low. They cited the overall positive phase 3 data. In a September 11 note, they stated, “It is difficult to speculate the motivation behind the FDA’s request for updated safety and efficacy data.”

Drug mechanism and other trials

Zanzalintinib is an oral multi-targeted kinase inhibitor. It works by binding to and inhibiting multiple receptor tyrosine kinases (RTKs). These enzymes are often dysregulated in cancer, driving abnormal cell growth and survival.

Exelixis is continuing to test the drug in other late-stage studies. The company has multiple ongoing phase 3 trials with zanzalintinib. These include studies in neuroendocrine tumors and non-clear cell renal cell carcinoma.

Analysts have projected significant future sales for the drug. They suggest zanzalintinib could generate $4.5 billion in U.S. Sales by 2033 across genitourinary and gastrointestinal cancers. If approved for mCRC, it would compete with existing therapies like Stivarga, Amgen’s Lumakras, and Takeda’s Fruzaqla.