Study did not demonstrate statistically significant improvement on primary endpoint of reduction in depressive symptoms as measured by MADRS total score compared to placebo
Navacaprant showed an efficacy signal in female participants; Company plans to further analyze results
Navacaprant generally well-tolerated with safety profile comparable to placebo
Neumora expects to share additional updates on navacaprant development program at J.P. Morgan Healthcare Conference; podium presentation Tuesday, January 14 at 8:15am PT
Jan. 02, 2025 -- Neumora Therapeutics, Inc. (Nasdaq: NMRA) a clinical-stage biopharmaceutical company with a therapeutics pipeline consisting of seven clinical and pre-clinical brain disease programs, today announced results from the Phase 3 KOASTAL-1 Study of navacaprant for the treatment of major depressive disorder (MDD). The KOASTAL-1 Study is the first of three replicate Phase 3 studies that comprise the pivotal KOASTAL program. The study did not demonstrate a statistically significant improvement on the primary endpoint of change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6 or the key secondary endpoint of a change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) scale.
“We are disappointed by the results from KOASTAL-1 as they were not consistent with the body of evidence supporting this mechanism in MDD. There is a lot to investigate from this study, in particular the contrast in drug and placebo responses in depressed mood and anhedonia in female participants compared to male participants,” said Rob Lenz, executive vice president, head of research and development, Neumora.
“We will not waver on our mission to make a difference for people living with brain diseases, which our broad pipeline of novel programs has the potential to address. The outcome of KOASTAL-1 is not what we expected, but there are encouraging trends in the data that we are analyzing,” said Henry Gosebruch, president and chief executive officer, Neumora. “Our strong financial foundation and cash balance of $342 million as of the end of the third quarter provides runway into mid-2026, and we look forward to providing additional updates on the navacaprant development program and our pipeline at the J.P. Morgan Healthcare Conference. We’d like to express our appreciation to the patients, families, and investigators who participated in this trial.”
The KOASTAL-1 study enrolled 383 adult patients with MDD. Topline efficacy results for navacaprant compared to placebo are outlined in the following table:
CFB = change from baseline; LSMD = difference in LS mean change from baseline between navacaprant and placebo groups generated from mixed-effects model for repeated measures. Subgroup analysis for male or female are pre-specified.
Navacaprant was shown to be safe and generally well-tolerated with no serious adverse events reported. There was no signal for increased suicidal ideation or suicidal behavior compared to placebo, as measured by Columbia Suicide Severity Rating Scale (C-SSRS).
Other notable TEAEs included pruritus (navacaprant 80 mg: 7 (3.7%), placebo: 4 (2.1%)).
Rates of treatment discontinuation due to TEAEs were low (navacaprant 80 mg: 2.1%, placebo: 3.1%).
A significant proportion (83.3%) of navacaprant 80 mg-treated patients who completed 6 weeks’ treatment elected to enroll in KOASTAL-LT.
The Phase 3 KOASTAL-2, KOASTAL-3 and KOASTAL-LT studies are ongoing.
The KOASTAL program includes three replicate Phase 3 randomized, placebo-controlled, double-blind studies, KOASTAL-1, KOASTAL-2, and KOASTAL-3, designed to evaluate the efficacy and safety of navacaprant monotherapy in adult patients with moderate-to-severe MDD who have a MADRS total score ≥ 25 at baseline. The KOASTAL-1 Study was conducted in the U.S. The KOASTAL-2 and -3 studies include sites in the U.S. and other regions. The primary endpoint of these studies is change from baseline in MADRS total score at Week 6. Key secondary endpoints include change from baseline on the SHAPS at Week 6, a measure of anhedonia.
The KOASTAL Program also includes an open-label extension study, KOASTAL-LT, designed to evaluate the long-term safety of navacaprant. As noted above, a significant portion of patients who received navacaprant 80 mg (83.3%) in the KOASTAL-1 study elected to enroll in KOASTAL-LT. Patients will also have the opportunity to enroll in the KOASTAL-LT study following participation in the KOASTAL-2 and KOASTAL-3 studies.
Navacaprant is a highly selective, novel kappa opioid receptor (KOR) antagonist being developed as a potential monotherapy treatment for MDD. Navacaprant is an investigational once-daily oral 80 mg medication that is designed to modulate the dopamine and reward processing pathways, which play an important role in the regulation of mood, cognition, reward, and behavior. The KOR system is a well-characterized pathway known to mediate depressive-like states, and modulating this system represents a novel approach to treating MDD and other major neuropsychiatric disorders.
MDD is a chronic psychiatric condition characterized by low mood and impairment in functioning, including episodes where an individual experiences a loss of interest or pleasure in daily activities and has symptoms such as problems with sleep, eating, energy, concentration or sense of self-worth. MDD is estimated to impact over 21 million adults in the United States, and women are nearly twice as likely as men to experience depression according to the National Alliance on Mental Illness. Nearly 70% of MDD patients fail to achieve remission with first-line treatment, which can be associated with negative side effects, including weight gain, sexual dysfunction, drowsiness, nausea and insomnia.
Anhedonia is a core feature of MDD impairing the capacity to experience or anticipate pleasure and is present in up to 70% of people with MDD. Anhedonia is associated with poor treatment outcomes and is frequently not resolved with currently approved therapies.
Neumora Therapeutics, Inc. is a clinical-stage biopharmaceutical company founded to confront the global brain disease crisis by taking a fundamentally different approach to the way treatments for brain diseases are developed. Our therapeutic pipeline currently consists of seven clinical and preclinical neuroscience programs that target novel mechanisms of action for a broad range of underserved neuropsychiatric disorders and neurodegenerative diseases. Our work is supported by an integrated suite of translational, clinical, and computational tools to generate insights that can enable precision medicine approaches. Neumora’s mission is to redefine neuroscience drug development by bringing forward the next generation of novel therapies that offer improved treatment outcomes and quality of life for patients suffering from brain diseases.
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