A phase 2b trial of HMNC Brain Health’s depression drug candidate has missed its primary endpoint. But while the ex-Sanofi molecule failed to move the needle in the pre-specified population, results in the overall population have convinced the German biotech to talk to regulators about a phase 3 program.
HMNC designed the phase 2b trial to assess the efficacy of BH-200, a vasopressin 1b receptor antagonist also known as nelivaptan, in major depressive disorder (MDD) patients with a dysregulated stress response. The company created a blood-based, genetic biomarker test to stratify patients. HMNC zeroed in on V1b-high patients for the primary analysis but also included V1b-medium and V1b-low patients in secondary cohorts.
After eight weeks of treatment, the V1b-high patients’ scores on the HAM-D17 depression scale were no better on BH-200 than on placebo, causing the study to miss its primary endpoint. Yet, the inclusion of V1b-medium and V1b-low patients offered HMNC a shot at redemption.
Contrary to its original hypothesis, HMNC reported the greatest clinical benefit in the subgroup with lower peripheral vasopressin activity. The company said the study results suggest that “lower peripheral vasopressin activity correlates with stronger central vasopressin activity in relevant brain areas, resulting in a more pronounced antidepressant response.”
As researchers have generated a clearer picture of the drivers of mental and neurological disorders, drug developers have embarked on precision programs designed to match the right medicine to the right patient. Advocates of the approach see it as a way to echo the transformation of cancer care, which has moved away from categorizing tumors solely by their location and toward molecularly targeted treatments.
Despite the primary endpoint miss, HMNC is forging ahead with its precision psychiatry program. The company is planning to talk to regulators about a phase 3 program and pursue its goal of making BH-200 the first precision-guided antidepressant in real-world practice.
Editor's note: This article was updated at 3:15 p.m. ET on Aug. 5 to correctly state which population the primary endpoint missed in.