Dazucorilant significantly extends survival in Phase 2 ALS trial
Therapy aims to set cortisol to reduce inflammation, prevent nerve cell damage
Dazucorilant, an oral cortisol modulator being developed by Corcept Therapeutics, significantly improved survival among people with amyotrophic lateral sclerosis (ALS) in a Phase 2 clinical trial.
Despite it failing to slow disease progression, the trial’s main goal, Corcept is now seeking guidance from U.S. and European regulators to determine the best path forward for its experimental therapy. The company shared updated trial findings at the European Network to Cure ALS (ENCALS) 2025 annual meeting in a presentation titled, “A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial of Dazucorilant, a Selective Glucocorticoid Receptor Modulator, in Amyotrophic Lateral Sclerosis.”
“Medications that can extend life for patients with ALS are urgently needed. We are working with regulatory authorities to determine the optimal path for advancing dazucorilant,” Bill Guyer, Corcept’s chief development officer, said in a company press release.
Cortisol is a hormone that’s made naturally in response to stress, and helps regulate blood pressure and metabolism, among other functions. Chronically elevated cortisol levels can cause nerve damage, however, and evidence suggests that people with ALS, particularly those with rapid disease progression, tend to have high cortisol.
Dazucorilant is designed to modulate cortisol activity by binding to the glucocorticoid receptor. This has been shown in animal models of ALS to reduce inflammation and prevent nerve cell damage.
Dazucorilant’s effect on survival
Corcept sponsored a Phase 2 clinical trial called DAZALS (NCT05407324) to test dazucorilant in people with ALS. The study enrolled 249 adults who were randomly assigned to take dazucorilant at one of two doses (150 or 300 mg), or a placebo, once daily for 24 weeks, or about six months. The participants could continue taking their standard ALS medications during the trial.
The study’s main goal was to see if dazucorilant could slow disease progression, as measured by a decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores. The results announced last year showed no significant difference between dazucorilant or a placebo.
A secondary goal was to evaluate dazucorilant’s effect on survival outcomes. During the study, none of the patients given the higher dose died, but two patients on the lower dose and five on the placebo did.
After the study, the participants could continue into an open-label extension where they’re all receiving 300 mg of dazucorilant for up to 2.5 years.
An exploratory analysis has compared the risk of death for those given the high dose and who continued to take it in the open-label extension against those given a placebo in the study and who didn’t enter the extension, meaning they never received dazucorilant. After a follow-up of up to 100 weeks, or about two years, 17% of patients always on 300 mg dazucorilant died compared with 39% on a placebo, meaning an 84% lower risk of death with dazucorilant.
A similar analysis compared patients who received at least 24 weeks of treatment with the 300 mg dose, either in the main trial or the extension, against those who received a placebo or the 150 mg dose for 24 weeks and didn’t enter the extension. Here, prolonged treatment with high-dose dazucorilant led to a 64% lower risk of death, a statistically significant reduction,
“The improvement in overall survival, first noted in the DAZALS study at six months, continues to be seen at one year. This finding deserves our full attention in service to patients with this tragic disease. Progress in the development of new ALS treatments is of critical importance,” said Leonard H. van den Berg, MD, PhD, principal investigator of the DAZALS study at UMC Utrecht Brain Center in the Netherlands.
The most common side effect of dazucorilant from the Phase 2 study was abdominal pain, which usually appeared within the first few weeks of starting treatment and resolved over time. Still, some had to discontinue treatment due to this side effect.
“Abdominal pain resolved following treatment interruption and, with time, in patients who continued treatment,” the researchers wrote.
The therapy did have an acceptable safety profile, with rates of serious and severe side effects being similar across the dazucorilant and placebo arms.
“We would like to thank the patients, their families and care partners, as well as the investigators, doctors, and clinic staff involved in this study,” Guyer said.
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