Cytokinetics will discontinue its Phase III COURAGE-ALS trial in amyotrophic lateral sclerosis (ALS) following a failed interim analysis.
A Data Monitoring Committee recommended terminating COURAGE-ALS (NCT04944784) after determining reldesemtiv had no effect on the primary endpoint of ALS Functional Rating Scale-Revised (ALSFRS-R) at 24-weeks. ALSFRS-R is a clinician assessment of ALS severity based on 12 aspects of physical function, including swallowing and breathing.
The interim analysis of COURAGE-ALS included over 200 patients that received reldesemtiv treatment for 24 weeks, meeting the criteria for a prescheduled follow-up. COURAGE-ALS had an enrollment goal of 555 patients, according to the trial listing, and Cytokinetics said around 460 patients had been enrolled at the time of the interim analysis.
COURAGE-ALS also met criteria for futility along key secondary endpoints, including a joint assessment of ALSFRS-R and survival outcomes. Regulators typically require Phase III trials in ALS to include measures of survival alongside ALSFRS-R.
In addition, Cytokinetics announced it will discontinue treatment in the ongoing open-label extension of COURAGE-ALS, called COURAGE-ALS-OLE (NCT05442775).
In 2019, reldesemtiv missed its primary endpoint in the 458-patient, Phase II FORTITUDE-ALS trial (NCT03160898). However, Cytokinetics found some positive signals that it said justified a larger Phase III trial in ALS. These included some improvements for reldesemtiv patients over placebo along ALSFRS-R and slow vital capacity (SVC).
Reldesemtiv is a small molecule administered as a twice daily pill. The therapy activates fast skeletal muscle troponin in order to increase contractility in patients with ALS. ALS is a rare, progressive neurodegenerative disease affecting approximately one in 50,000 people.
Busy year for ALS drug development
Following an eventful year of ALS drug development in 2022, this year has already seen several key catalyst events. Last month, an FDA Advisory Committee (AdCom) overwhelmingly supported an accelerated approval for Biogen’s tofersen to treat a rare form of ALS.
Meanwhile, the FDA also announced plans to hold an AdCom meeting to discuss an ALS stem cell therapy candidate NurOwn from BrainStorm Cell Therapeutics. The FDA had previously rejected NurOwn’s approval application in 2022 before changing course last month.
Nevertheless, the failed Phase III trial of reldesemtiv represents a tough blow to the ALS community in dire need of new treatments as the FDA looks to build momentum in rare disease approvals.