Antiseizure Agent BHV-7000 Demonstrates Positive Safety, Efficacy Results in Phase 1 Study

Author(s):

Findings from the study further confirmed target engagement of BHV-7000, with future plans of a potential phase 3 trial in focal epilepsy later this year.

Vlad Coric, MD

Biohaven recently announced results from its exploratory phase 1 electroencephalogram (EEG) biomarker study demonstrating that BHV-7000, its investigational lead candidate, was well tolerated among healthy volunteers, with dose-dependent and time-dependent increases in brain spectral power. Based on these data, along with other findings from other single- and multiple-ascending dose studies, the company plans to explore 3 oral doses of BHV-7000 in a phase 3 program of focal epilepsy.¹

BHV-7000 is a novel and selective activator of Kv7.2/Kv7.3, a key ion channel involved in neuronal signaling and in regulating the hyperexcitable state. In the trial, healthy volunteers were assigned single doses of 10, 25, or 50 mg of the agent, with qualitative changes in EEG spectral power as the main end point. For context, EEG spectral power is a measure derived from EEG signals that assess the amount of rhythmic activity in different frequency bands, including delta (1-3.5 Hz), theta (3.5-7.5 Hz), alpha (7.5-13 Hz), beta (13-30 Hz), and gamma (30-100 Hz).

The data, which was presented to epilepsy key opinion leaders at an off-site meeting held during the 2023 International Epilepsy Conference in Dublin, Ireland, showed that BHV-7000 was well tolerated, with a safety profile that was consistent with previously reported single (SAD)- and multiple-ascending dose (MAD) study data. At the lowest dose of 10 mg (n = 12), participants with BHV-7000 concentrations greater than EC50 demonstrated mean increases in EEG spectral power in beta and gamma bands that were not observed in participants with drug concentrations less than EC50.

"The EEG results presented are an important milestone after almost a decade of effort by the ion channel discovery team, led by Drs. Michael Bozik and Steven Dworetzky, to develop a highly selective Kv7.2/7.3 activator with a best-in-class drug profile," Vlad Coric, MD, chairman and chief executive officer at Biohaven, said in a statement.¹ "The EEG data confirms central nervous system target engagement as measured by dose-dependent changes in spectral power in expected frequency bands and over the entire head."

Among 11 individuals treated with a higher dose of 50 mg BHV-7000, increases in EEG spectral power were observed across all spectral bands and distributed over all cortical brain regions. In this dosed group, the time course of the increase in EEG spectral power corresponded with the known pharmacokinetic profile of BHV-7000.

In previously completed phase 1 SAD and MAD studies, the therapy was shown to maintain its safe profile in single doses up to 100 mg and multiple doses up to 80 mg daily. Headache, dizziness, and myoclonus were all reported AEs; however, investigators did not observe other AEs such as somnolence, speech disorder, and memory impairment that are typically associated with antiseizure medications.

"These EEG results along with the safety data from the Phase 1 studies and our formulation group's development of a once-daily extended-release drug formulation of BHV-7000, allow us to advance to pivotal trials later this year," Coric added.¹ "We are excited about evaluating the efficacy of this highly selective Kv7.2/7.3 activator in epilepsy, mood disorders (including bipolar disorder) and other diseases as the profile of BHV-7000 represents a potential paradigm shift for this mechanism of action."

BHV-7000, formerly known as KB-3061, is also being studied as a treatment of KCNQ2 developmental and epileptic encephalopathy, a rare, debilitating disease that manifests in infants and children as early-onset seizures and encephalopathy because of a defect in the function of the Kv7.2 channel caused by pathogenic mutations in the KCNQ2 gene. Additionally, there are several other early-stage studies underway focused on mood and pain disorders based on increasing evidence in the literature.²

REFERENCES
1. Biohaven announces positive data from its exploratory electroencephalogram (EEG) biomarker study of BHV-7000 completion of once-daily formulation development, and plan to initiate phase 3 pivotal studies. News release. Biohaven Pharmaceuticals. September 5, 2023. Accessed October 17, 2023. https://www.prnewswire.com/news-releases/biohaven-announces-positive-data-from-its-exploratory-electroencephalogram-eeg-biomarker-study-of-bhv-7000-completion-of-once-daily-formulation-development-and-plan-to-initiate-phase-3-pivotal-studies-301917174.html
2. Kv7 channel modulation platform. Biohaven Pharmaceuticals. Accessed October 17, 2023. https://www.biohaven.com/pipeline/clinical-programs/kv7/