Dazucorilant Shows 2-Year Survival Benefit in Phase 2 ALS Trial Despite Missing Primary End Point

In a new company update, Corcept Therapeutics has announced 2-year overall survival findings from the phase 2 DAZALS study (NCT05407324) evaluating its proprietary, selective cortisol modulator dazucorilant in patients with amyotrophic lateral sclerosis (ALS). The company reported a significant reduction in mortality risk among patients with ALS treated with the agent despite the trial not meeting its primary end point of functional improvement.¹

DAZALS was a randomized, double-blind, placebo-controlled phase 2 trial that enrolled 249 patients with ALS, who were assigned to receive either 150 mg or 300 mg of dazucorilant, or placebo, daily for 24 weeks. The primary end point was change in function as measured by the ALS Functional Rating Scale–Revised and overall survival was assessed as a secondary end point. Despite not missing the primary end point, investigators observed a statistically significant improvement in overall survival at 24 weeks in patients who received 300 mg of dazucorilant compared with placebo (P = .02).

Exploratory analyses further suggested that the survival benefit associated with dazucorilant may extend beyond the treatment period. Patients who completed the initial 24-week study were eligible to enroll in a long-term extension phase, during which all participants received 300 mg of the therapy. Corcept noted that these extended data may help inform ongoing development efforts, including planned discussions with regulatory authorities and a potential phase 3 trial.

“ALS remains an area of significant unmet need and observing a sustained overall survival benefit at one and two years is highly encouraging. Data demonstrate that dazucorilant can reduce early mortality following diagnosis – a time where many people with ALS retain meaningful function and quality of life,” Bill Guyer, PharmD, chief development officer at Corcept, told NeurologyLive^®. “We are working with regulators to advance this program as quickly as possible and expect to initiate a pivotal phase 3 study in late 2026. We are currently conducting a dose titration study to refine methods of improving dazucorilant’s tolerability.”

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Longer-term follow-up analyses suggested a sustained effect on mortality risk. At 2 years following treatment initiation, patients originally assigned to 300 mg of dazucorilant experienced an 87% reduction in risk of death compared with patients who received placebo and did not transition to active treatment in the extension phase (hazard ratio [HR], 0.13; P <.0001). These findings were consistent with earlier results observed at 1 year, where a reduction in mortality risk of 84% was reported (HR, 0.16; P = .0009). The 1-year data were previously presented at the 2025 European Network to Cure ALS annual meeting, held June 3–6, in Turin, Italy.²

Additional subgroup analyses evaluated outcomes among patients who received prolonged exposure to 300 mg of dazucorilant, either during the initial study period or in the extension phase. In these analyses, patients treated with the higher dose for more than 24 weeks demonstrated a 64% reduction in risk of death at 1 year (HR, 0.36; P = .02) and a 61% reduction at 2 years (HR, 0.39; P = .02), compared with patients who received placebo or the lower dose and did not receive dazucorilant during the extension phase.

Safety findings from the trial indicated that dazucorilant was generally well tolerated. The most commonly reported adverse event was abdominal pain, which was described as mild to moderate, dose-related, and transient. Previously, the company reported that no deaths were reported in the 300-mg group compared with 5 deaths in the placebo group, during the 24-week study period (P = .02).³

“People living with ALS exhibit elevated or abnormal cortisol levels. Dazucorilant is a selective cortisol modulator that binds to the glucocorticoid receptor (GR) but not to the body’s other hormone receptors. It is the only GR modulator in development for people with ALS,” Guyer added. “Because of its distinct mechanism of action dazucorilant has the potential to be combined with existing standards of care and emerging treatment options. In addition, it is not genetically selective and may have broad applicability.”

REFERENCES
1. Corcept Phase 2 Study of Dazucorilant Demonstrates Two-Year Overall Survival Benefit in Patients with Amyotrophic Lateral Sclerosis. News release. Corcept Therapeutics. April 30, 2026. Accessed May 4, 2026. https://ir.corcept.com/news-releases/news-release-details/corcept-phase-2-study-dazucorilant-demonstrates-two-year-overall
2. Corcept Presents Results from Phase 2 Study of Dazucorilant in Patients with Amyotrophic Lateral Sclerosis (ALS) at ENCALS 2025 Annual Meeting. News release. Corcept Therapeutics. June 5, 2025. Accessed May 4, 2026. https://ir.corcept.com/news-releases/news-release-details/corcept-presents-results-phase-2-study-dazucorilant-patients-0/
3. Corcept Announces Results From Phase 2 Study of Dazucorilant in Patients With Amyotrophic Lateral Sclerosis (ALS). News release. Corcept Therapeutics. December 11, 2024. Accessed May 4, 2026. https://ir.corcept.com/news-releases/news-release-details/corcept-announces-results-phase-2-study-dazucorilant-patients