Corcept’s dazucorilant fails to slow ALS progression in clinical trial
Phase 2 DAZALS study enrolled 249 adults at multiple sites
Dazucorilant, an oral cortisol modulator being developed by Corcept Therapeutics, didn’t significantly slow disease progression in people with amyotrophic lateral sclerosis (ALS) over a placebo, meaning it failed to meet the primary goal of the DAZALS Phase 2 clinical trial.
The study (NCT05407324), which tested dazucorilant doses at 150 mg or 300 mg in 249 participants, also showed that gastrointestinal side effects at the start of treatment were “substantially” more common with dazucorilant than a placebo.
No deaths were reported in the high-dose group after six months, but five deaths were in the placebo group, a statistically meaningful difference. The participants are now being treated in the open-label extension and more mature survival data will be collected when all have reached a year of treatment, which is expected by March.
Complete results from DAZALS will be presented next year at a scientific conference, the company said in a press release.
There’s increasing evidence that people with ALS, particularly those with rapidly progressive disease, have abnormally elevated cortisol levels. Cortisol is a steroid hormone that’s important for regulating blood pressure, metabolism and blood sugar levels, and the body’s anti-inflammatory processes. It’s normally produced in response to stressful conditions to help the keep the body alert and deal with them, but constantly elevated cortisol levels can lead to nerve cell damage.
Studying dazucorilant in ALS
Dazucorilant is a cortisol modulator made to block the interaction between cortisol and glucocorticoid receptors, which interrupts cortisol signaling and should mitigate the harmful effects of excessive cortisol in ALS.
In animal models of ALS, daily administration of dazucorilant reduced inflammation and prevented nerve cell damage. Treated mice also had better motor function and less muscle wasting over those who didn’t receive treatment.
DAZALS was launched to determine if similar benefits were observed in people with the disease. It enrolled 249 adults at sites across the U.S., Canada, and Europe who were randomly assigned to receive one of two dazucorilant doses or a placebo for about six months. They could continue to receive their standard ALS medications.
Along with establishing whether dazucolirant could slow disease progression after six months, which wasn’t met, another main goal has been to see if dazucorilant is safe and well tolerated. Secondary measures included changes in muscle strength, respiratory function, and overall quality of life.
After completing DAZALS, participants could enter an open-label extension study, where all are being given the 300 mg dose for about 2.5 years.
Dazucorilant had been granted fast track status by the U.S. Food and Drug Administration, which is meant to accelerate the development and review of medicines for serious conditions. It provides certain incentives to companies, such as more frequent meetings with the agency to discuss its development plan, guidance of clinical trial design, and eligibility tooward streamlining the approval process.