Corcept’s Phase 2 Trial of Dazucorilant Shows Sustained Two-Year Survival Advantage in ALS Patients
Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage biopharmaceutical company focused on developing therapies that modulate cortisol activity, has reported new long-term data from its Phase 2 DAZALS clinical trial evaluating dazucorilant in patients with amyotrophic lateral sclerosis (ALS). The updated findings highlight a sustained survival benefit over a two-year period, reinforcing earlier observations and supporting continued development of the investigational therapy.
The DAZALS study was designed as a randomized, double-blind, placebo-controlled Phase 2 trial involving 249 patients diagnosed with ALS. Participants were assigned to receive either 150 mg of dazucorilant, 300 mg of dazucorilant, or a placebo once daily for a 24-week treatment period. Following completion of this phase, eligible participants were allowed to enroll in a long-term extension phase, during which all patients received the higher 300 mg dose of dazucorilant. The study’s primary endpoint focused on changes in functional status, measured using the ALS Functional Rating Scale–Revised (ALSFRS-R), while overall survival was included as a key secondary endpoint.
Although the trial did not meet its primary endpoint of demonstrating a statistically significant improvement in functional outcomes compared to placebo, the survival data emerging from the study have drawn considerable attention. At the end of the 24-week treatment period, patients receiving the 300 mg dose of dazucorilant showed a statistically significant improvement in overall survival compared with those receiving placebo, with a p-value of 0.02. This early signal prompted further investigation into long-term outcomes.
Subsequent exploratory analyses have demonstrated that the survival advantage associated with the higher dose of dazucorilant not only persisted but became more pronounced over time. Over a two-year period following the initiation of treatment, patients who received 300 mg of dazucorilant experienced an 87 percent reduction in the risk of death compared to those in the placebo group who did not transition to active treatment during the extension phase.
This corresponds to a hazard ratio of 0.13 and a highly significant p-value of less than 0.0001. These results build upon previously reported one-year data, which showed an 84 percent reduction in mortality risk (hazard ratio: 0.16; p-value: 0.0009), findings that were presented at the European Network to Cure ALS (ENCALS) annual meeting in 2025.
Further subgroup analyses provided additional insights into the durability of the treatment effect. Patients who received the 300 mg dose for more than 24 weeks—either during the initial treatment phase or after transitioning into the extension phase—continued to show a meaningful survival benefit when compared with patients who remained on placebo or received the lower 150 mg dose without subsequent escalation. In this comparison, the risk of death was reduced by 64 percent at the one-year mark (hazard ratio: 0.36; p-value: 0.02) and by 61 percent at two years (hazard ratio: 0.39; p-value: 0.02). These consistent findings across multiple analyses suggest that sustained exposure to the higher dose of dazucorilant may be critical to achieving optimal therapeutic benefit.
From a safety perspective, dazucorilant has continued to demonstrate a tolerable profile in patients with ALS. The most frequently reported adverse event has been mild to moderate abdominal pain, which appears to be dose-related and transient in nature. To further improve gastrointestinal tolerability, Corcept is currently conducting a dose titration study aimed at optimizing dosing strategies and minimizing side effects. Insights from this effort are expected to inform the design and execution of future trials.
The mechanism of action of dazucorilant—selective modulation of cortisol activity—represents a novel approach in ALS, a disease with limited treatment options and a high unmet medical need. By targeting pathways associated with stress hormone signaling, the therapy may influence neuroinflammation and neuronal survival, although the exact mechanisms underlying the observed survival benefit remain an area of ongoing research.
Company leadership has expressed optimism regarding the implications of these findings. According to Corcept’s Chief Development Officer, the data indicate that dazucorilant has the potential to significantly reduce mortality during the early years following diagnosis, a period when patients typically retain a greater degree of physical function and quality of life. This aspect is particularly important in ALS, where disease progression is often rapid and debilitating.
Corcept is actively engaging with regulatory authorities to determine the most efficient path forward for the program. Based on the strength and consistency of the survival data, the company anticipates initiating a pivotal Phase 3 clinical trial later this year. The upcoming study is expected to further evaluate the efficacy and safety of dazucorilant, with a focus on confirming the survival benefit and potentially supporting regulatory approval.
In summary, while the DAZALS trial did not achieve its primary functional endpoint, the compelling survival outcomes observed with the 300 mg dose of dazucorilant over both one- and two-year periods provide a strong rationale for continued clinical development. If confirmed in larger, late-stage trials, these findings could mark an important advancement in the treatment landscape for ALS, offering hope for improved outcomes in a condition that currently has few effective therapeutic options.
About the DAZALS Study
DAZALS is a randomized, double-blind, placebo-controlled Phase 2 trial in which 249 patients with ALS were randomized 1:1:1 to receive either 150 mg of dazucorilant, 300 mg of dazucorilant or placebo daily for 24 weeks. Patients who completed the treatment period were eligible to enroll in the study’s long-term extension phase, in which all patients received 300 mg of dazucorilant. Baseline patient characteristics, including the ENCALS risk score, time from diagnosis, ALSFRS-R total score, and bulbar onset, were consistent across study arms.
The DAZALS primary endpoint was the difference in change from baseline during the study’s 24-week treatment period in ALSFRS-R score between patients who received dazucorilant and those who received placebo. Key secondary endpoints include overall survival and quality of life. DAZALS was conducted at sites in Europe, the United States and Canada.
About Amyotrophic Lateral Sclerosis
ALS, also known as Lou Gehrig’s disease or motor neuron 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 not to the body’s other hormone receptors. Corcept is studying dazucorilant as a potential treatment for ALS and other neurologic disorders. The compound is proprietary to Corcept and is protected by composition of matter, method of use and other patents. The U.S. Food and Drug Administration has granted dazucorilant Fast Track Designation and orphan drug status for the treatment of ALS in the United States.
About Corcept Therapeutics
For over 25 years, Corcept has focused on cortisol modulation and its potential to treat patients with a wide variety of serious disorders and has discovered more than 1,000 proprietary selective cortisol modulators and glucocorticoid receptor antagonists. Corcept is conducting advanced clinical trials in patients with Cushing’s syndrome, solid tumors, ALS and liver disease. In 2012, the company introduced Korlym®.
The first medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with endogenous Cushing’s syndrome, and in 2026, the company introduced Lifyorli™, approved in combination with nab-paclitaxel, the first FDA-approved selective glucocorticoid receptor antagonist, for adults with platinum-resistant ovarian cancer. Corcept is headquartered in Redwood City, California.
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