Neumora's navacaprant Phase 3 completes with KOASTAL-2 data still unreported
The MDD trial finished and enrollment reset to 430, but topline results Neumora guided to Q2 2026 have not landed as a prior Phase 3 kappa antagonist for depression already failed.
Executive Summary
- Neumora Therapeutics' Phase 3 trial of navacaprant in major depressive disorder has finished, with its enrollment count reconciled to target, but the topline result the company told investors to expect this quarter has not been reported.
- The trial tests whether blocking the kappa opioid receptor can separate from placebo on a validated depression symptom scale, in a mechanism class where a same-target Phase 3 program has already failed to reach approval.
- The completion and the enrollment reconciliation are routine registry housekeeping and do not by themselves signal trouble; the primary completion date held within its prior guided range and the trial closed enrollment on the total it needed.
- Navacaprant is one of three programs, alongside Janssen's aticaprant and AbbVie's icalcaprant, actively testing kappa opioid receptor antagonism in major depressive disorder, making this readout informative for the entire mechanism class, not just Neumora.
- The data are the story now, not the calendar, and the trial's completed status means Neumora is positioned to disclose a result rather than to explain another delay.
The trial and its bar
NCT06058013 is a randomized, quadruple-masked, placebo-controlled Phase 3 study testing oral navacaprant against placebo in adults with major depressive disorder, with 430 patients enrolled across the United States, Brazil, Canada and Chile. The primary endpoint is the change from baseline to Week 6 in the Montgomery-Asberg Depression Rating Scale total score, a standard measure of depressive symptom severity, with a secondary endpoint on the Snaith-Hamilton Pleasure Scale capturing anhedonia. Neumora has repeatedly told investors it expected topline data from this trial, alongside its companion KOASTAL-3 study, in the first half of 2026, most recently reaffirming a second-quarter window for KOASTAL-2. NCT06058013+1Study to Assess the Effects of Oral NMRA-335140 Versus Placebo in Participants With Major Depressive DisorderNCT06058013Neumora Therapeutics Reports First Quarter 2025 Financial Results and Provides Business UpdateMay 12, 2025
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What completed
The trial's status changed from Active, not recruiting to Completed on July 6, 2026, and its enrollment count was updated the same day from an anticipated 332 to an actual 430. That reconciliation reflects the registry catching up to the trial's already-enrolled total rather than a new enrollment decision; the operational model that tracks enrollment moves against design classifies the underlying change as typical for this design. The primary completion date moved once, from January 2025 to May 2026, a shift that predates the current readout window and does not by itself indicate new instability. NCT06058013Study to Assess the Effects of Oral NMRA-335140 Versus Placebo in Participants With Major Depressive DisorderNCT06058013
The mechanism's history
Kappa opioid receptor antagonism has a Phase 3 track record in this exact pairing: of eight Phase 3 trials targeting OPRK1 in major depressive disorder, three have terminated, a 38% failure rate for the target-indication combination. Neumora's own earlier Phase 2 trial of navacaprant reported statistically significant reductions in depression and anhedonia symptoms versus placebo, the result the company has cited as the basis for advancing to Phase 3. Janssen Research & Development's aticaprant is running a parallel Phase 3 program in the same indication and target, and AbbVie's icalcaprant is in Phase 2, making navacaprant's result one input into how the field reads the mechanism's viability going forward. NeumoraNeumora Therapeutics Reports First Quarter 2025 Financial Results and Provides Business UpdateMay 12, 2025
What the readout tests
Because the trial uses a placebo control, quadruple masking and a validated symptom-severity scale as its primary measure, a positive result would need to show a MADRS reduction that separates from placebo with a magnitude consistent with what the Phase 2 study demonstrated. Given the class's 38% Phase 3 termination rate in this pairing, a result that merely trends in the right direction without separating clearly from placebo would leave the mechanism's viability in this indication as unresolved as it is now.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.