After failing to hit the primary endpoint in a Phase III trial, Neumora is remixing study parameters in two replicate trials, with data expected in the first half of 2026.
Neumora Therapeutics has temporarily halted two Phase III trials of its depression drug, navacaprant, to make adjustments after the drug failed in a different Phase III study in January.
In the KOASTAL-1 trial, treatment with navacaprant did not demonstrate a statistically significant improvement in symptoms of depression after six weeks in patients with major depressive disorder.
Navacaprant is a kappa opioid receptor (KOR) antagonist, designed to modulate dopamine and reward processing pathways, with the hopes of improving mood and cognition.
The two delayed trials, dubbed KOASTAL-2 and KOASTAL-3, were initially planned as replicate studies of KOASTAL-1. Neumora is now reducing the number of sites used, adding medical monitoring provided by Massachusetts General Hospital Trials network, and implementing a screening tool to prevent people who enroll in multiple clinical trials at once from participating in the KOASTAL trials.
“We believe these changes strengthen the studies and look forward to delivering topline data in 2026,” Berns said in the company’s Q4 and full-year 2024 earnings report.
Once those changes are made, the company expects to restart the trials and have data from KOASTAL-3 in Q1 2026, and KOASTAL-2 in Q2, 2026. In Neumora’s original timeline, the KOASTAL-1, -2, and –3 trials would have had data ready to support a new drug application (NDA) for navacaprant in 2025.
In the same announcement, Neumora also said it was discontinuing a separate Phase II trial for navacaprant in bipolar depression in order to devote more resources to the KOASTAL trials.
Analysts appeared unperturbed by the shake-ups. William Blair’s team reminded readers in a note Monday afternoon that “based on analyses of KOASTAL-1, management believes further optimization of site selection and enhanced medical monitoring are required to ensure the appropriate patient enrollment in the KOASTAL program.”
In addition to navacaprant, Neumora also has a few other drugs coming down the pike. Its Alzheimer’s disease agitation drug, NMRA-511, a vasopressin 1a receptor (V1aR) antagonist, is currently in a Phase Ib study with data expected by the end of 2025. Another molecule, NMRA-266 for schizophrenia, was placed on clinical hold by the FDA in April 2024 when rabbits given the drug developed convulsions.
