Corcept's Dazucorilant Shows 87% Reduction in Death Risk for ALS Patients Despite Missing Primary Endpoint
核心洞察
Corcept Therapeutics' dazucorilant demonstrated an 87% reduction in death risk after two years in ALS (搜索) patients receiving 300mg daily compared to placebo in the Phase II DAZALS study.
The trial failed to meet its primary endpoint of functional improvement as measured by ALSFRS-R scores at 24 weeks, but showed significant survival benefit as a key secondary endpoint.
The company plans to initiate a pivotal Phase III study later this year following discussions with regulators to advance the selective cortisol modulator program.
Corcept Therapeutics' experimental ALS (搜索) treatment dazucorilant has demonstrated remarkable survival benefits in a Phase II trial, showing an 87% reduction in the risk of death after two years despite failing to meet its primary functional endpoint.
Significant Survival Benefit Observed
In the Phase II DAZALS study (NCT05407324), ALS (搜索) patients who received 300mg of dazucorilant, a selective cortisol modulator, experienced an 87% reduction in the risk of death after two years compared to patients who received placebo. This finding builds on the 84% reduction in risk of death observed after one year of treatment, demonstrating consistent survival benefits over time.
The randomized, double-blind, placebo-controlled study enrolled 249 patients to receive either 150mg of dazucorilant, 300mg of dazucorilant, or placebo. While the trial did not meet its primary endpoint of difference in function as measured by the ALS (搜索) Functional Rating Scale – Revised (ALSFRS-R) at the end of the 24-week treatment period, patients who received 300mg of dazucorilant daily exhibited improved overall survival, a key secondary endpoint.
Safety Profile and Adverse Events
The drug continued to demonstrate an acceptable safety profile throughout the study. The most common adverse event was mild to moderate, dose-related, transient abdominal pain. No significant safety concerns emerged during the two-year follow-up period.
Path to Phase III Development
Bill Guyer, Corcept's chief development officer, emphasized the clinical significance of these findings. "Our data demonstrate that dazucorilant markedly reduces mortality in the first years following diagnosis, when people with ALS (搜索) retain meaningful function and quality of life," Guyer said. "We are working with regulators to advance this programme as expeditiously as possible and expect to initiate a pivotal Phase III study later this year."
Expanding ALS Research Landscape
The positive results come amid accelerating interest in ALS (搜索) therapeutic development. Analysis by GlobalData found that clinical research activity in ALS has expanded considerably in recent years, with trial activity reaching its highest level in 2025, accounting for roughly 9% of all studies. Approximately 59% of trials have been completed, 9% are currently ongoing and recruiting participants, while another 9% are planned.
This momentum is reflected in other recent successes in the field. AL-S (搜索) is advancing its monoclonal antibody AP-101 to a registrational study after it prolonged survival and delayed ventilatory support after 12 months of treatment in a Phase II trial. Similarly, Spinogenix (搜索)'s lead candidate SPG302 met its primary endpoint in a Phase IIa study of safety and tolerability, with no treatment-emergent serious adverse events reported over six months of daily dosing.
Current Treatment Landscape
ALS (搜索) has historically been a challenging indication to treat, but there are now four therapies and an additional two prodrugs that have gained approval from the US Food and Drug Administration. This includes Biogen and Ionis Pharmaceuticals (搜索)' SOD1 (搜索)-targeting antisense oligonucleotide Qalsody (tofersen), which received accelerated approval from the FDA in 2023 despite the VALOR trial failing to meet its primary endpoint of improved ALSFRS-R scores over 28 weeks. The FDA granted approval based on changes in plasma levels of neurofilament light protein.