Biohaven Ltd. (NYSE: BHVN) presented expanded safety data from its BHV-7000 multiple-dose studies at the American Epilepsy Society (AES) 2024 Annual Meeting, showcasing a promising safety profile and potential efficacy for epilepsy treatment. The data, including results from Phase 1 multiple ascending dose studies with a once-daily extended-release formulation, suggest that BHV-7000 is well-tolerated without the central nervous system (CNS) adverse effects commonly seen with other anti-seizure medications (ASMs).
Favorable Safety and Tolerability
Jason Lerner, M.D., Medical Director and Epilepsy Clinical Lead at Biohaven, stated, "We are encouraged to see BHV-7000 continue to demonstrate favorable safety and tolerability without dose-limiting toxicities or CNS adverse events commonly associated with other ASMs, such as somnolence." The Phase 1 data showed that BHV-7000 was safe and well-tolerated at dose levels up to 120 mg daily for 15 days, with most adverse events being mild and resolving spontaneously. Notably, there were low rates of CNS-related adverse events, and no somnolence or cognitive/mood disturbances were reported.
Addressing Unmet Needs in Epilepsy
In addition to the clinical data, Biohaven presented a qualitative assessment of the epilepsy patient experience through social media and web-based forums. This assessment revealed that while seizure freedom remains the primary goal, patients also expressed significant concerns about ASM-associated adverse events, mental health challenges, and the stigma associated with epilepsy. The most frequently discussed adverse events included sleepiness, insomnia, mood changes, and cognitive effects, all of which negatively impact patients' quality of life.
Novel Mechanism of Action
BHV-7000 is a selective Kv7.2/7.3 activator, a key ion channel involved in neuronal signaling. Nonclinical data presented at AES detailed the pharmacological characterization of BHV-7000 using all-optical electrophysiology, demonstrating its potent in vitro effects to reduce neuronal activity. Furthermore, in vitro studies assessing the effects of BHV-7000 on 50 loss-of-function KCNQ2 variants showed that BHV-7000 rescued current density in all tested pathogenic variants, restoring it to wild-type levels for most variants. These findings support the potential therapeutic value of BHV-7000 in KCNQ2-related epilepsy.
Innovative Trial Design
Biohaven is currently advancing five ongoing pivotal Phase 2/3 trials with BHV-7000, including studies in focal epilepsy and idiopathic generalized epilepsy (IGE). The SHINE study (NCT06425159), a Phase 2/3 randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of BHV-7000 in IGE with generalized tonic-clonic seizures, employs an innovative, patient-centric design with an FDA-endorsed time-to-event endpoint. This design aims to decrease time on placebo, potentially reducing the risk of exposure to additional seizures, injury, and Sudden Unexpected Death in Epilepsy (SUDEP).
Dr. Lerner added, "The evidence to date with BHV-7000 represents a potential paradigm shift in the treatment of epilepsy as many patients continue to be burdened by adverse events and do not achieve adequate seizure control with existing medications."
