Equillium's GVHD Drug Misses Primary Endpoint, Company Still Pursues FDA Approval

Equillium, a biotechnology company focused on developing novel therapies for severe autoimmune and inflammatory disorders, has reported mixed results from its phase 3 trial of itolizumab in acute graft-versus-host disease (GVHD). Despite missing the primary endpoint and two key secondary objectives, the company remains optimistic about the drug's potential and plans to seek FDA approval.

Trial Results and Implications

The phase 3 study, which enrolled 158 adults and adolescents with acute GVHD, compared the anti-CD6 antibody itolizumab against placebo. The primary endpoint of complete response (CR) rate at Day 29 was not met, with itolizumab achieving a 43% CR rate compared to 48.1% for placebo. Additionally, two critical secondary endpoints - overall response rate at Day 29 and durable CR at Day 99 - failed to show statistical significance.

However, Equillium highlighted positive outcomes in other areas of the trial:

• Median duration of CR was significantly longer in the itolizumab group (336 days) compared to placebo (72 days).
• Failure-free survival showed improvement in the treatment arm.
• Post hoc analyses, including durable CR evaluating Day 29 complete responders and CR at Day 99 (after removing three patients who did not receive treatment), yielded positive results.
• A positive trend in overall survival was observed, with a death rate of 24.4% in the itolizumab group versus 32.5% in the placebo group.

Regulatory Strategy and Financial Outlook

Despite the mixed results, Equillium is pursuing an aggressive regulatory strategy:

1. The company has filed for breakthrough therapy designation with the FDA.
2. A meeting with the FDA is scheduled to discuss the potential for accelerated approval.
3. Equillium expects to receive feedback from the agency in May.
4. If the FDA provides encouragement, the company plans to file for approval in the first half of 2026.

The pursuit of FDA approval comes at a critical time for Equillium, as the company faces financial pressures. With $22.6 million in cash reserves at the end of the previous year, Equillium estimates it can sustain operations only into the third quarter of the current year. The news of the missed primary endpoint has already impacted investor confidence, with the company's stock price dropping 13% in premarket trading to $0.66.

Industry Context and Next Steps

Equillium's situation highlights the challenges faced by smaller biotechnology companies in bringing novel therapies to market. The company's decision to continue pursuing approval despite missing key endpoints underscores the complex nature of drug development, particularly in areas with high unmet medical needs such as GVHD.

As Equillium awaits feedback from the FDA, the pharmaceutical industry will be watching closely to see how regulators respond to the company's arguments for approval based on secondary endpoints and post hoc analyses. The outcome of this process could have implications for other companies developing treatments for rare and complex diseases, where traditional clinical trial designs may not always capture the full potential benefit of a therapy.