Unveiling Boundless Horizons: Unlocking BHV-7000’s Potential in Epilepsy

• Biohaven with BHV-7000 underscores unwavering commitment to neurology and to addressing unmet patient needs, by providing innovative therapeutic choices with improved tolerability for epilepsy patients. 
• BHV-7000, a selective activator of Kv7.2/7.3 potassium channels, presents a promising avenue, navigating the complexities often associated with existing anti-seizure medications by reducing the side effects in the central nervous system. 

At the recently concluded American Academy of Neurology Annual Meeting (2024) Biohaven presented abstracts elucidating the characterization of their primary candidate within the Kv7 platform, BHV-7000, as a prospective treatment for seizures. These abstracts highlighted the pharmacodynamic impact of BHV-7000 on electroencephalogram (EEG) spectral power in healthy adult subjects and the safety and tolerability of single and multiple ascending doses (SAD and MAD) of oral BHV-7000. BHV-7000 is a clinically validated target in epilepsy, that has demonstrated potent anti-seizure properties in maximal electroshock seizure model, with no observable adverse effects on neurobehavioral functioning or motor abilities.

In the Phase I trial, BHV-7000 demonstrated promising safety and tolerability, characterized by minimal activation of GABA_A receptors. Conducted at a single center, the trial employed a double-blind, placebo-controlled design and administered sequential single and multiple ascending doses (SAD/MAD) of BHV-7000 to healthy adults aged 18-55. Participants were randomly assigned in a 3:1 ratio to receive BHV-7000 at doses ranging from 4 to 100 mg or placebo for SAD, and 10 to 40 mg or placebo for MAD, administered daily for 15 days. Throughout the trial, subjects underwent sequential EEG recordings using the international 10-20 electrode setup on several designated days. Common adverse events included headache, abdominal discomfort, and back pain, with low occurrences of central nervous system-related adverse events; notably, no reports of somnolence were documented. 

The majority of adverse events were mild and resolved spontaneously, and no deaths, serious adverse events, severe adverse events, or dose-limiting toxicities were observed. These findings demonstrated that BHV-7000 was safe and well tolerated showcasing its effectiveness in epilepsy models with a wide therapeutic index to explore full dose range. These results emphasize the potential of BHV-7000 to alleviate undesired central nervous system side effects by modulating GABA_A receptor activation, thereby presenting patients with a promising and convenient therapeutic option for refractory focal epilepsy. 

Biohaven’s BHV-7000 represents a potential leading candidate among selective Kv7 activators, holding considerable promise for neurological and neuropsychiatric conditions such as epilepsy. Distinguished both structurally and pharmacologically from existing potassium channel activators, BHV-7000 promises to herald a new chapter in the annals of Epilepsy management. Its efficacy in neuropsychiatric models akin to ketamine highlights its potential to enhance patients’ quality of life by enabling greater autonomy in their daily activities. It’s just the beginning for Biohaven, which needs to cross the scrutiny of trials, the success rate where is bleak, and many have failed to see the light of dawn.