In a Phase 2 study, navacaprant (NMRA-140) monotherapy demonstrated statistically significant and clinically meaningful reductions in symptoms of depression and anhedonia in participants with moderate-to-severe MDD
Pivotal studies expected to support New Drug Application for navacaprant monotherapy in 2025. (Credit: Luis Melendez on Unsplash)
Neumora Therapeutics, Inc. (Neumora), a clinical-stage biopharmaceutical company redefining neuroscience drug development, today announced the planned initiation of the KOASTAL Program, a Phase 3 pivotal clinical program designed to evaluate the efficacy and safety of navacaprant (NMRA-140) monotherapy for the treatment of major depressive disorder (MDD). The planned initiation follows the successful completion of an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) and a robust Phase 2 study with navacaprant. Navacaprant is an oral 80 mg once-daily kappa opioid receptor (KOR) antagonist, a novel mechanism of action for the monotherapy treatment of MDD.
“The planned initiation of the KOASTAL program represents an important step toward our goal of bringing a truly novel treatment to people living with MDD,” said Paul L. Berns, co-founder and executive chairman, Neumora. “The data from our Phase 2 study with navacaprant demonstrate its potential as a differentiated antidepressant that may help to manage anhedonia in addition to other core symptoms of depression with a favorable safety profile. These symptoms are among the most challenging to treat and cause significant negative impact on patients’ quality of life. Patients deserve better treatment options for depression, and we are working with urgency to address the serious unmet medical need that remains in MDD.”
The KOASTAL Program will include three Phase 3 randomized, placebo-controlled, double-blind studies, KOASTAL-1, KOASTAL 2, and KOASTAL 3, designed to evaluate the efficacy and safety of navacaprant mono therapy inadult patients with moderate-to-severe MDD who have a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥ 25 at baseline. The primary endpoint of these studies will be a change from baseline in MADRS total score at Week 6. The key secondary endpoints will be change from baseline on the Snaith-Hamilton Pleasure Scale (SHAPS) at Week 6, a measure of anhedonia.
The KOASTAL Program will also include an open-label extension study, KOASTAL-LT, designed to evaluate the long-term safety of navacaprant. Patients will have the opportunity to enroll in the KOASTAL-LT study following participation in the KOASTAL-1, KOASTAL-2, or KOASTAL-3 studies. If successful, these studies are expected to support a New Drug Application (NDA) with the FDA for navacaprant monotherapy in 2025.
“Navacaprant has a novel mechanism of action that modulates multiple neurotransmitters, including dopamine, in reward processing pathways and may offer a differentiated monotherapy treatment option beyond the currently approved agents,” said Sanjay J. Mathew, M.D., vice chair for research and professor of psychiatry and behavioral sciences at Baylor College of Medicine. “I’m excited by the Phase 2 data with navacaprant that demonstrate statistically significant and clinically meaningful improvements in depressive and anhedonic symptoms in traditionally studied moderate-to-severe MDD patients. I’m also impressed with the response in the total population, which included patients with mild MDD, and the well-tolerated safety profile. These data support the important role that the kappa opioid receptor system may have in regulating mood and addressing significant unmet needs for MDD patients.”
Source: Company Press Release