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FDA delays decision on Exelixis' colorectal cancer drug zanzalintinib

FDA delays decision on Exelixis' colorectal cancer drug zanzalintinib

Rule Changes

Three-month extension moves the PDUFA decision to March 2027

Yesterday: Exelixis discloses delay; shares slip

Overview

Updated Yesterday

Exelixis learned on September 10 that the FDA would delay its decision on zanzalintinib, its experimental colorectal cancer drug, by three months. The new deadline is March 3, 2027, after the agency deemed updated safety and efficacy data a major amendment to the application.

The drug, paired with Roche's immunotherapy atezolizumab (Tecentriq), is Exelixis' best chance at a second franchise after the blockbuster Cabometyx. If approved, it would be the first immunotherapy-based regimen to show an overall survival benefit in metastatic colorectal cancer patients who are not MSI-high, the large majority of cases.

Why it matters

The FDA's March 2027 decision determines whether Exelixis launches its next cancer drug or cedes ground to regorafenib and fruquintinib in late-line colon cancer.

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Key Indicators

March 3, 2027
New PDUFA action date
Extended from December 3, 2026 after the FDA deemed the amended application a major change.
901
Patients in STELLAR-303 trial
Randomized to zanzalintinib plus atezolizumab or regorafenib in the Phase III study supporting the application.
20%
Reduction in risk of death in the trial
Median overall survival was 10.9 months versus 9.4 months for regorafenib (hazard ratio 0.80, P=0.0045).

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Organizations Involved

Timeline

October 2025 September 2026

5 events Latest: Yesterday
Tap a bar to jump to that date
  1. Exelixis discloses delay; shares slip

    Latest Regulatory

    Exelixis files with SEC; shares fall about 2%. New decision date is March 3, 2027.

  2. FDA notifies Exelixis of three-month extension

    Regulatory

    FDA tells Exelixis it will extend the review after updated data filed.

  3. Secondary analysis misses statistical bar

    Trial Results

    Analysis in patients without liver metastases shows non-significant survival trend, hazard ratio 0.83.

  4. FDA accepts new drug application

    Regulatory

    FDA accepts Exelixis' application covering previously treated metastatic colorectal cancer patients.

  5. STELLAR-303 results presented at ESMO Congress

    Trial Results

    Phase III trial shows zanzalintinib plus atezolizumab improves overall survival versus regorafenib.

Scenarios

1

FDA approves zanzalintinib on March 3, 2027

Likely Resolves by Mar 3, 2027

Discussed by: William Blair, which kept an Outperform rating and sees a low chance of outright rejection

The FDA accepts the amended data and grants approval based on the statistically significant overall survival benefit in the full trial population, which randomized 901 patients. The missed secondary endpoint in patients without liver metastases may narrow the label, but William Blair sees this as the most likely outcome because the primary analysis did meet its bar.

2

FDA issues a complete response letter

Unlikely Resolves by Mar 3, 2027

Discussed by: Investors focused on the missed non-liver-metastases endpoint

The FDA concludes the amended application raises questions requiring another trial, issues a complete response letter (a rejection with stated reasons), and sends Exelixis back for more data. William Blair sees this as unlikely because the main endpoint reached statistical significance, but the June 2026 miss keeps it on the table.

3

FDA extends the review again

Possible Resolves by Mar 3, 2027

Discussed by: Market observers tracking the amended-application pattern

The FDA requests further information, pushing the PDUFA date beyond March 3, 2027. This would mirror the current amendment-driven extension and delay any US launch deeper into 2027.

Historical Context

2 moments from history that rhyme with this story — and how they unfolded.

September 2012

Regorafenib (Stivarga) approval (2012)

The FDA approved regorafenib as the first treatment for metastatic colorectal cancer that had progressed after standard therapy. Approval rested on the CORRECT trial, where the drug extended median overall survival from 5.0 to 6.4 months.

Then

Regorafenib became the standard third-line option and remains one today.

Now

It set the benchmark for late-line colon cancer drugs and is the comparator arm in Exelixis' STELLAR-303 trial.

Why this matters now

Zanzalintinib was tested directly against regorafenib, and the 1.5-month median survival advantage it showed echoes the modest benefits the FDA has accepted in this exact setting.

November 2023

Fruquintinib (Fruzaqla) approval (2023)

The FDA approved fruquintinib, a vascular endothelial growth factor receptor inhibitor, for refractory metastatic colorectal cancer based on the global FRESCO-2 trial showing median overall survival of 7.4 months versus 4.8 months with placebo.

Then

Fruquintinib gave US patients a new oral option in late-line colon cancer.

Now

It joined regorafenib and trifluridine/tipiracil as one of the approved options zanzalintinib would compete with.

Why this matters now

The FDA has approved multiple kinase inhibitors in this space despite modest survival gains, suggesting approval odds for zanzalintinib remain meaningful even with imperfect secondary data.

Sources

(7)