Biohaven's bipolar treatment doesn't improve mania in key trial

Biohaven Pharmaceuticals recently announced the outcomes of a pivotal trial involving their investigational treatment for bipolar disorder, BHV-7000. Conducted over three weeks, this phase 2/3 study focused on individuals with bipolar I disorder. Participants were administered either 75 mg of BHV-7000 or a comparator daily. The trial's key objective was to evaluate the reduction in mania symptoms using the Young Mania Rating Scale, which consists of 11 elements to assess these symptoms.

Disappointingly, the trial results indicated that BHV-7000 did not show a statistically significant improvement in reducing mania symptoms compared to the comparator. This outcome was shared in Biohaven's quarterly earnings report on March 3. Although detailed data from the trial were not disclosed, the company mentioned that further analyses are being conducted. Biohaven plans to present the complete data set at an upcoming scientific event.

Despite the setback in efficacy, BHV-7000 was well tolerated by participants. There were no serious treatment-emergent adverse events reported, with most side effects being mild and resolving on their own. Analysts from William Blair noted the drug's attractive tolerability profile, particularly its lack of central nervous system (CNS) side effects like dizziness, which are commonly associated with other antiseizure and psychiatric medications.

BHV-7000 is part of Biohaven's Kv7 platform, designed to selectively activate the Kv7.2/Kv7.3 ion channel, crucial for neuronal signaling and regulation. The company is also exploring the potential of BHV-7000 as a treatment for pain disorders. Currently, the investigational drug is undergoing three other phase 2/3 trials in major depressive disorder (MDD), focal epilepsy, and generalized epilepsy. The results for MDD are anticipated in the latter half of this year, while findings for focal epilepsy are expected in the first half of next year. According to William Blair analysts, the data on MDD will be significant in establishing the drug’s competitive positioning in the emerging Kv7-potentiator space.

In a separate announcement on the same day, Biohaven shared early-stage clinical results for another candidate, BHV-1300, a subcutaneous small molecule. This phase 1 trial revealed that administering 1000 mg of BHV-1300 weekly led to an 84% reduction in total IgG levels among patients with Graves’ disease, a figure that slightly surpasses the reductions achieved with other subcutaneously administered FcRN-targeted therapies. For instance, Immunovant's IMVT-1402 showed a 74% mean IgG reduction with weekly dosing in a phase 1 trial involving healthy individuals.

Biohaven's four-week study found BHV-1300 to be safe and well tolerated. The drug is a protein degrader specifically designed to target IgG1, 2, and 4, while sparing IgG3. As noted by Biohaven's Chief Translational Officer, Dr. Tova Gardin, this groundbreaking extracellular degrader technology utilizes the body’s natural hepatic clearance mechanisms to eliminate disease-contributing antibodies. This approach has the potential to herald a new era of personalized, selective, and self-administered immune therapies.

Looking ahead, Biohaven plans to initiate a phase 2 trial of BHV-1300 for Graves’ disease by mid-2025, with further studies targeting other autoimmune diseases expected. Following the trial results announcement, Biohaven's stock experienced a decline, dropping 14% from $36.95 at market open to $32 by the close of the day.