Neumora Therapeutics Shares KOASTAL-1 Study Results on Navacaprant for Major Depression

On January 2, 2025, Neumora Therapeutics, Inc., a biopharmaceutical company focused on brain diseases, released results from their Phase 3 KOASTAL-1 study. This research aimed to assess navacaprant's efficacy in treating major depressive disorder (MDD). Navacaprant, a novel kappa opioid receptor antagonist, is being developed as a potential monotherapy for MDD, a condition affecting over 21 million adults in the U.S.

The KOASTAL-1 study, part of a larger KOASTAL program including three Phase 3 trials, did not achieve its primary goal. The study aimed to demonstrate a statistically significant improvement in reducing depressive symptoms, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), over six weeks. Similarly, it did not meet the key secondary endpoint of change in anhedonia, which was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS).

Despite the overall results, navacaprant showed an efficacy signal in female participants, prompting further analysis by the company. Navacaprant was generally well-tolerated, with safety comparable to a placebo. No serious adverse events were reported, and there was no increase in suicidal thoughts compared to the placebo group. Notably, a common side effect was pruritus, occurring in a small percentage of both treatment and placebo groups.

The KOASTAL-1 study enrolled 383 adult patients with moderate-to-severe MDD, defined by a baseline MADRS score of 25 or higher. Participants were randomly assigned to receive either navacaprant or a placebo. Subgroup analyses by gender were pre-specified, revealing significant observations among female participants. Despite the lack of statistical significance in primary and secondary endpoints, navacaprant's potential benefits in specific subgroups are under further examination.

Henry Gosebruch, Neumora's CEO, expressed disappointment in the KOASTAL-1 outcomes but highlighted encouraging trends within the data. The company's strong financial position, with a $342 million cash balance, supports ongoing research and development efforts. Neumora remains committed to its mission of advancing treatments for brain diseases, as illustrated by its continued work on navacaprant and a diverse portfolio of other programs addressing neuropsychiatric disorders.

Neumora plans to provide updates on navacaprant's development at the upcoming J.P. Morgan Healthcare Conference. The company's pipeline consists of seven clinical and preclinical programs targeting novel mechanisms to tackle various brain diseases. These initiatives are underpinned by advanced translational, clinical, and computational tools, aiming to enable precision medicine approaches in neuroscience.

The KOASTAL program, beyond KOASTAL-1, includes the ongoing KOASTAL-2 and KOASTAL-3 studies. These trials continue to evaluate navacaprant's efficacy and safety in MDD patients. Additionally, the KOASTAL-LT study offers an open-label extension to assess long-term safety. A significant number of KOASTAL-1 participants opted to join KOASTAL-LT, reflecting interest in navacaprant's potential benefits.

Navacaprant represents a novel approach to treating MDD by modulating the dopamine and reward processing pathways. This method targets a well-characterized system associated with depressive-like states, offering a potential new direction in MDD treatment. MDD is marked by persistent low mood and impaired functioning, often accompanied by anhedonia, a core symptom affecting up to 70% of patients. Traditional therapies frequently fail to address anhedonia, highlighting the need for innovative treatments like navacaprant.

Neumora Therapeutics is devoted to transforming neuroscience drug development with the goal of improving outcomes and quality of life for patients with brain diseases. With a deep focus on innovative therapies, Neumora aims to redefine treatment paradigms in the field of neuropsychiatry.