Corcept's ALS Candidate Shows Survival Benefit, Misses Primary Endpoint

Event summary

  • Corcept's Phase 2 DAZALS study of dazucorilant in ALS patients randomized 249 patients to receive 150mg, 300mg of dazucorilant, or placebo for 24 weeks, with extension to 300mg for all.
  • While the study did not meet its primary endpoint (ALSFRS-R score improvement), patients receiving 300mg of dazucorilant daily showed improved overall survival.
  • Two-year data reveal an 87% reduction in the risk of death (HR: 0.13, p<0.0001) for patients on 300mg dazucorilant compared to placebo.
  • Corcept plans to initiate a pivotal Phase 3 study later in 2026, preceded by a dose titration study to improve gastrointestinal tolerability.

The big picture

ALS treatment remains a significant unmet medical need, with limited therapeutic options. While the failure to meet the primary endpoint is a setback, the robust survival benefit observed with dazucorilant represents a potentially significant advancement, particularly given the disease's aggressive progression and limited life expectancy. Corcept's focus on cortisol modulation represents a novel approach to ALS, potentially opening new avenues for therapeutic intervention beyond existing symptomatic treatments.

What we're watching

Regulatory Pathway
The FDA's acceptance of the survival data as sufficient for accelerated approval will hinge on the perceived clinical significance of the benefit versus the lack of primary endpoint achievement, potentially influencing the design of the Phase 3 trial.
Phase 3 Design
The design of the Phase 3 trial will be critical; Corcept's choice of endpoints and patient selection criteria will need to balance the need for statistical significance with clinical relevance, given the existing survival benefit.
Commercialization
The success of Corcept's commercialization efforts will depend on demonstrating a clear value proposition to physicians and patients, particularly given the high cost of ALS therapies and the relatively short life expectancy of patients.

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Pharmaceuticals Drug Development Biotechnology