Authors :
Presenting Author: Bharat Awsare, MD – Biohaven Pharmaceuticals
Jason Lerner, MD – Biohaven Pharmaceuticals
Eric Ashbrenner, MS – Biohaven Pharmaceuticals
Heather Sevinsky, MS – Biohaven Pharmaceuticals
Michael Bozik, MD – Biohaven Pharmaceuticals
Steven Dworetzky, PhD – Biohaven Pharmaceuticals
Christopher Jensen, PharmD – Biohaven Pharmaceuticals
Randall Killingsworth, BA – Biohaven Pharmaceuticals
Andrea Ivans, MHS – Biohaven Pharmaceuticals
Irfan Qureshi, MD – Biohaven Pharmaceuticals
Vladimir Coric, MD – Biohaven Pharmaceuticals
Rationale:
Adverse events (AEs) of antiseizure medications (ASMs), including CNS AEs such as somnolence and cognitive/mood disturbances, negatively impact quality of life and treatment adherence; there remains a continued need for efficacious ASMs with minimal AE burden. BHV-7000 is a novel, small molecule, selective activator of Kv7.2/7.3 potassium channels in late-stage clinical development for epilepsy and neuropsychiatric disorders. In preclinical studies, BHV-7000 demonstrated minimal GABAA receptor activation and exhibited potent anti-seizure efficacy in the maximal electroshock seizure model without negative effects on neurobehavior or motor function. A Phase 1 EEG study confirmed CNS target engagement of BHV-7000 at predicted therapeutic concentrations. Initial Phase 1 safety studies demonstrated favorable safety and tolerability of BHV-7000 with no dose-limiting AEs. The objective of this analysis was to assess the safety and tolerability of BHV-7000 across multiple ascending dose (MAD) studies completed to date.
Methods:
Results were pooled from Phase 1 placebo-controlled MAD studies. Healthy adults aged 18-55 years were enrolled and randomized to BHV-7000 immediate release tablets (10, 25, 40, 80, or 120 mg daily), extended-release tablets (25, 50, or 75 mg daily), or matching placebo, and treated for up to 15 days. Safety evaluations throughout the studies included AE monitoring, clinical laboratory tests, vital signs, ECGs, physical examinations, and Sheehan Suicidality Tracking Scale. A Safety Review Committee assessed the safety and tolerability after completion of each dose level prior to dose escalation.
Results:
Across the MAD cohorts, 66 participants received BHV-7000 (N=53) or placebo (N=13). Adverse events occurring in ≥5% of participants across the pooled BHV-7000 cohorts are presented in Table 1. There were low rates of CNS-related AEs; no somnolence was reported. The majority of AEs were mild and resolved spontaneously. There were no deaths, serious AEs, severe AEs, or dose-limiting toxicities. No AEs were reported among participants receiving BHV-7000 75 mg extended release (n=12), the highest dose currently utilized in Phase 2/3 studies.
Conclusions:
BHV-7000 was well tolerated in multiple-dose Phase 1 studies across all doses evaluated, without AEs typically associated with other anti-seizure medications. These findings support the continued clinical development of BHV-7000 as a novel ASM with the potential to reduce seizures while minimizing AEs. Patients are currently being enrolled in multiple Phase 2/3 studies evaluating the efficacy and safety of BHV-7000 in focal and generalized epilepsy as well as neuropsychiatric disorders.
Funding:
This study was funded by Biohaven.