Corcept Therapeutics (Nasdaq: CORT) reported two-year overall survival data from its Phase II DAZALS study of dazucorilant in amyotrophic lateral sclerosis (ALS), showing an 87% reduction in risk of death compared to placebo in patients receiving the 300 mg dose — a result that, if it holds in a confirmatory trial, would mark the first time a glucocorticoid receptor-targeted agent has demonstrated a survival benefit in ALS.
What the DAZALS Study Found
The DAZALS trial is a randomized, double-blind, placebo-controlled Phase II study that enrolled 249 patients with ALS across sites in the US, Europe, and Canada, randomizing them 1:1:1 to dazucorilant 150 mg, dazucorilant 300 mg, or placebo daily for 24 weeks, with an optional long-term extension in which all participants received 300 mg.
The trial did not meet its primary endpoint — the difference in change from baseline in ALSFRS-R functional score over the 24-week treatment period. That caveat matters. The survival data now being highlighted by Corcept come from a secondary endpoint and subsequent exploratory analyses, not from a positive primary readout. In the two years following treatment initiation, patients who received 300 mg dazucorilant showed an 87% reduction in risk of death compared to placebo patients who did not switch to 300 mg in the extension phase (hazard ratio: 0.13; p < 0.0001). That signal is consistent with the one-year data presented at the ENCALS 2025 annual meeting, where the reduction in risk of death was 84% (HR: 0.16; p = 0.0009).
A secondary analysis comparing patients who received 300 mg for more than 24 weeks — whether in the treatment period or the extension — against those who received placebo or 150 mg for more than 24 weeks and did not enter the extension showed a 61% reduction in risk of death at two years (HR: 0.39; p = 0.02), consistent with the 64% reduction seen at one year (HR: 0.36; p = 0.02). The safety profile remained acceptable, with mild to moderate, dose-related, transient abdominal pain as the most frequently reported adverse effect. Corcept is running a separate dose titration study to address gastrointestinal tolerability and inform Phase III design.
Dazucorilant ALS Mechanism: A Different Angle on a Difficult Disease
The rationale for targeting cortisol modulation in a neurologic disorder like ALS rests on accumulating evidence that patients with ALS — particularly those with rapid disease progression — exhibit elevated or dysregulated cortisol levels. Dazucorilant is a selective cortisol modulator that binds the glucocorticoid receptor (GR; NR3C1) without engaging other hormone receptors, an approach designed to blunt cortisol-driven GR signaling while avoiding the broad systemic effects associated with non-selective glucocorticoid agents.
That mechanism places dazucorilant in a category with no currently approved ALS therapy. The three drugs on the market — riluzole (which targets glutamate excitotoxicity and has been standard of care since 1995), edaravone (a free radical scavenger approved in 2017), and tofersen (Qalsody [tofersen], an antisense oligonucleotide approved in 2023 for the roughly 2% of patients with SOD1 mutations) — operate through entirely distinct pathways. None targets the cortisol-GR axis. The withdrawal of Relyvrio (AMX0035) from the US market in April 2024, following Phase III failure, further narrowed the approved armamentarium and removed the only combination neuroprotective agent that had reached approval.
The absence of a GR-directed therapy in ALS means that if the survival signal from DAZALS is confirmed in a randomized Phase III trial, the compound would occupy mechanistically distinct territory from every currently available option.