Dazucorilant

It’s been a tough few months for Corcept Therapeutics. In October, the company’s lead pipeline candidate missed the primary endpoint in a Phase 3 Cushing’s syndrome trial. Now, its only neurology asset has flunked a mid-stage study in amyotrophic lateral sclerosis, possibly marking the end of the road for the program. The California biotech’s dazucorilant did not meet the primary endpoint of change from baseline in an ALS functional rating scale in the 249 patient-strong placebo-controlled Phase 2 study. Subjects who received the treatment also had “substantially more” stomach upset than placebo patients, according to a company release Thursday. Corcept appeared to claim signs of a survival benefit for the 300 mg dose of dazucorilant, pointing out that no one in this arm died, compared with five deaths for placebo. However, in light of the primary endpoint failure, this is likely to carry little weight, particularly since survival was not a specified endpoint on the trial’s protocol as listed on clinicaltrials.gov. The company said it plans to share full Phase 2 results at a medical meeting in 2025. Meanwhile, its open-label extension study of the drug will continue as normal, with overall survival to be evaluated in March 2025. Dazucorilant, a selective cortisol modulator, binds to the glucocorticoid receptor while avoiding the body’s other hormone receptors, Corcept said. In February, CEO Joseph Belanoff told investors the drug had “shown great promise” in ALS animal models, improving motor symptoms and reducing muscular atrophy. ALS treatments have managed to clear regulatory hurdles in the past with less-than-stellar results. In 2022, the FDA approved Amylyx’s ALS drug Relyvrio based on results from a single mid-stage trial and post hoc analyses, after much back and forth and two advisory committee meetings. But the drug then failed a Phase 3 test earlier this year, prompting Amylyx to voluntarily pull it from the market and terminate around 70% of staff to help reduce costs.

REDWOOD CITY, Calif.--( BUSINESS WIRE )--Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic, and neurologic disorders by modulating the effects of the hormone cortisol, today announced results from the DAZALS study, a randomized, double-blind, placebo-controlled, Phase 2 trial evaluating two doses (150 mg and 300 mg) of its proprietary selective cortisol modulator dazucorilant in patients with ALS. Upon completion of the trial, patients were eligible to enter an open-label, long-term extension study, in which they received 300 mg of dazucorilant. DAZALS did not meet its primary endpoint, which was the change from baseline in the ALS Functional Rating Scale-Revised (ALSFRS-R) in patients who received dazucorilant compared to those who received placebo. Patients who received dazucorilant experienced substantially more gastrointestinal upset at the onset of treatment than those who received placebo. During the 24-week study, no deaths (0/83) were observed in the 300 mg arm, compared to 5 deaths (5/82) in the placebo group (p-value: 0.02). The open-label, long-term extension study will continue and overall survival will be assessed in March 2025 after all patients have had one year pass since the onset of treatment. Dazucorilant has been granted Fast Track Designation by the U.S. Food and Drug Administration. Complete results from the DAZALS study will be presented at a medical conference next year. About the DAZALS Study DAZALS enrolled 249 patients, randomized 1:1:1 to receive either 150 mg of dazucorilant, 300 mg of dazucorilant or placebo daily for 24 weeks. The study’s primary endpoint was to slow the decline in motor skills and other functional criteria, compared to placebo, as measured by the ALSFRS-R. Key secondary endpoints include overall survival and quality of life. Patients were provided the opportunity to receive 300mg of dazucorilant for 132 weeks in the open-label, long-term extension of the DAZALS study. DAZALS is being conducted at sites in Europe, the United States and Canada. About Amyotrophic Lateral Sclerosis (ALS) ALS, also known as Lou Gehrig’s disease, is a fatal degenerative neurologic disorder that affects more than 55,000 people in the United States and Europe. ALS causes muscles to weaken and, as the disease progresses, severely impairs patients’ ability to speak, eat, move and breathe. There is increasing evidence that patients with ALS, particularly those with rapid disease progression, exhibit elevated or abnormal cortisol levels. A patient’s life expectancy after diagnosis is two to five years. About Dazucorilant Dazucorilant is a selective cortisol modulator that binds to the glucocorticoid receptor but does not bind to the body’s other hormone receptors. Corcept is studying it as a potential treatment for ALS and other neurologic disorders. Dazucorilant is proprietary to Corcept and is protected by composition of matter, method of use and other patents. About Corcept Therapeutics For over 25 years, Corcept’s focus on cortisol modulation and its potential to treat patients with a wide variety of serious disorders has led to the discovery of more than 1,000 proprietary selective cortisol modulators. Corcept is conducting advanced clinical trials in patients with hypercortisolism, solid tumors, ALS and liver disease. In February 2012, the company introduced Korlym ® , the first medication approved by the U.S. Food and Drug Administration for the treatment of patients with endogenous hypercortisolism. Corcept is headquartered in Redwood City, California. For more information, visit Corcept.com. Forward-Looking Statements Statements in this press release, other than statements of historical fact, are forward-looking statements based on our current plans and expectations, which are subject to risks and uncertainties that might cause our actual results to differ materially from those such statements express or imply. These risks and uncertainties are set forth in our SEC filings, which are available at our website and the SEC’s website. In this press release, forward-looking statements include those concerning the development of dazucorilant as a treatment for patients with ALS, including the pace, conduct, timing and outcome of DAZALS and its associated long-term extension study, as well as oversight or requirements that may be imposed by the FDA or other regulatory authorities. We disclaim any intention or duty to update forward-looking statements made in this press release.