Biohaven didn’t receive the clinical readout it was hoping for over the festive period. As the biopharma wound down for the holidays, the company reported the failure of a midphase study of BHV-7000 for the treatment of major depressive disorder (MDD).
The study, which aimed to enroll 300 patients, compared the selective activator of Kv7.2/7.3 potassium channels to placebo. After six weeks of daily treatment, the drug candidate was no better at alleviating depressive symptoms, as measured on the Montgomery-Åsberg Depression Rating Scale.
William Blair analysts said in a note to investors that they “were cautious heading into this study given difficulties in clinical trial execution and placebo creep in trials over recent years.” The analysts added that the efficacy of ezogabine, which GSK pulled (PDF) from the market in 2017, and Xenon Pharmaceuticals’ azetukalner “have not left much room for effect size erosion in pivotal trials of KV7.2/7.3 potentiator molecules.”
Yet the analysts were still disappointed by the Biohaven failure. While the company saw trends favoring BHV-7000 in some clinically relevant subgroups, the analysts warned against overinterpreting the results given the small number of patients in the analysis. Patients with severe depression performed better on BHV-7000 than placebo on multiple measures, but the subgroup included fewer than 30 participants.
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Biohaven said the subgroup analyses are hypothesis-generating. However, amid a pipeline prioritization push, the company has opted against running additional psychiatric clinical trials. Biohaven is currently focused on immunology, obesity and epilepsy studies.
The analysts removed BHV-7000 in MDD from their Biohaven model and are awaiting pivotal data on the molecule in focal onset epilepsy to inform further changes. The data, which are due in the first half of 2026, could help answer the question of whether Biohaven’s extended-release formulation is active in the central nervous system (CNS).
Investors have debated whether switching between immediate- and extended-release formulations has changed CNS exposure, the analysts said. The debate reflects the 0% rate of sleepiness in phase 1 trials. The failure of the MDD trial, coupled with the balanced rate of adverse events across the BHV-7000 and placebo arms, did “little to assuage” concerns about CNS exposure, the analysts said.
Biohaven reported headache rates of 10.7% and 9.9% in the BHV-7000 and placebo cohorts, respectively. Nausea affected 4.2% of people on BHV-7000, compared to 5.6% on placebo. No other individual adverse event occurred with an incidence above 5%.
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The MDD failure removes a potential competitor to azetukalner, Xenon’s KV7 potassium channel opener. Xenon is running a phase 3 program for the drug candidate in MDD. The analysts said the doubts about BHV-7000’s CNS exposure likely limit any negative read-through from Biohaven’s failure to Xenon’s azetukalner program.
Biohaven shares fell when news of the failure broke Dec. 24. Yet the stock rebounded when trading resumed Dec. 26, and Biohaven shares closed the year at $11.39—slightly higher than they were going into the MDD readout.
