HMNC Brain Health Pursues Precision Depression Treatment Despite Phase 2b Setback

HMNC Brain Health, a German biotech company, is pressing forward with its precision psychiatry program for major depressive disorder (MDD) despite a recent setback in its phase 2b clinical trial. The company's drug candidate, BH-200, failed to meet its primary endpoint in the study's target population but showed promise in unexpected subgroups, prompting HMNC to recalibrate its approach and engage regulators about a potential phase 3 program.

Trial Results and Unexpected Findings

The phase 2b trial, designed to assess the efficacy of BH-200 (also known as nelivaptan) in MDD patients with a dysregulated stress response, utilized a blood-based genetic biomarker test to stratify patients into V1b-high, V1b-medium, and V1b-low categories. Contrary to the initial hypothesis, the primary endpoint was not met in the V1b-high patient group, with no significant improvement in HAM-D17 depression scale scores compared to placebo after eight weeks of treatment.

However, the study yielded an unexpected finding: the greatest clinical benefit was observed in the subgroup with lower peripheral vasopressin activity. HMNC reported that this result suggests "lower peripheral vasopressin activity correlates with stronger central vasopressin activity in relevant brain areas, resulting in a more pronounced antidepressant response."

Implications for Precision Psychiatry

The mixed results from HMNC's trial highlight both the challenges and potential of precision psychiatry. As researchers gain a deeper understanding of the molecular drivers of mental disorders, drug developers are increasingly adopting strategies to match specific treatments to patient subgroups, mirroring the evolution seen in cancer care.

BH-200, a vasopressin 1b receptor antagonist originally developed by Sanofi, represents HMNC's bid to create the first precision-guided antidepressant for real-world practice. Despite the primary endpoint miss, the company remains committed to this goal, viewing the unexpected subgroup results as a basis for further development.

Next Steps and Regulatory Engagement

HMNC Brain Health is now planning discussions with regulatory authorities regarding a potential phase 3 program for BH-200. The company will likely need to refine its patient selection criteria and potentially adjust its therapeutic strategy based on the phase 2b findings.

As the field of precision psychiatry continues to evolve, HMNC's experience underscores the importance of flexibility in clinical development. The company's willingness to recalibrate its approach in light of new data may prove crucial in navigating the complex landscape of targeted therapies for mental health disorders.