Corcept Therapeutics’ amyotrophic lateral sclerosis drug was linked to an 87% reduction in the risk of death, a result the biotech hopes to replicate in an upcoming Phase 3 trial.
Corcept Therapeutics has linked its amyotrophic lateral sclerosis drug to a lower risk of death after two years of treatment, offering further support for the biotech’s hypothesis as the therapy enters Phase 3.
The Phase 2 study compared two doses of dazucorilant, a cortisol modulator, to placebo in 249 people with the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Primary results from the study found that dazucorilant had no significant effect on motor skills and other functional criteria after 24 weeks of treatment, causing the trial to miss its primary endpoint. Yet an early survival signal encouraged Corcept to run an extension study.
During the 24-week study, none of the 83 patients on the high, 300-mg dazucorilant dose died. Five of the 82 patients on placebo died.
A subsequent update showed the divergence persisted in the first year of the extension study. After one year, 14 of the 83 patients on the 300-mg dose had died, compared to 7 of the 18 placebo patients who opted against joining the long-term extension study. The result equated to an 84% reduction in the risk of death. Corcept essentially replicated the result in its two-year analysis, reporting an 87% reduction in the risk of death.
The biotech reported similarly consistent outcomes in its comparison of participants who received the 300-mg dose for more than 24 weeks and patients who took the 150-mg dose or placebo for 24 weeks. Corcept linked the 300-mg dose to reductions in the risk of death of 64% and 61%, respectively, in the one- and two-year analyses.
Corcept is preparing to test dazucorilant in a Phase 3 trial. The goal is to “confirm that dazucorilant can reduce early death and improve survival,” William Guyer, Corcept’s chief development officer, said on the biotech’s first-quarter earnings call Thursday. The trial will study the 300-mg dose and likely use placebo as a control, Guyer said.
The use of the 300-mg dose creates a tolerability challenge. Almost 58% of patients who received the dose during the initial 24-week study had an adverse event that led them to discontinue treatment, with gastrointestinal side effects cited as the main concern.
Corcept is conducting a small study to see if dose titration can improve dazucorilant’s gastrointestinal tolerability, CEO Joseph Belanoff said on the call. Belanoff thinks the non-serious gastrointestinal distress that caused most of the discontinuations can be avoided. Corcept plans to incorporate the findings of the dose-titration study into a pivotal trial that is expected to start this year, the CEO said.
