Insights on Biohaven’s New Phase 2/3 Trial of Potassium Inhibitor BHV-7000 for Treating Focal Epilepsy

Aliza Alter, MD

While there are several different types of antiseizure medications available, some patients still struggle to control seizures, even after trying numerous treatments. One agent in development, Biohaven’s BHV-7000, has shown promise in early-stage studies, and now gears up for a new phase 2/3 trial. The newly announced Rise 1 and 2 trials span 96 sites across the US and will assess the efficacy, safety, and tolerability of this drug in patients with focal onset epilepsy.

Prior to this study, the therapy showed a dose-dependent pharmcodynamic effect on EEG parameters in a phase 1 study of healthy adults. That study comprised of a single-ascending dose and multiple-ascending dose cohort, where 61 healthy volunteers received BHV-7000 (n = 46) or placebo. Results showed that as increases in spectral power were observed in treated patients, the incidence of central nervous system (CNS) AEs remained low. Above all, there were low rates of nervous system treatment-emergent adverse events during the 15-day period.

For more insight on the newly initiated phase 2/3 study, NeurologyLive® reached out to principal investigator Aliza Alter, MD, a pediatric neurologist at the Institute of Neurology in Livingston, New Jersey. Alter gave thoughts and perspective on the outline of the trial, the challenges with treating focal epilepsy, and the unique mechanism of action of BHV-7000. Furthermore, she provided some knowledge on who may be eligible for the study, and what treatment regimens may look like during participation.

NeurologyLive: For clinicians, what are the most notable aspects of this trial?

Aliza Alter, MD: The Rise clinical trials are national randomized, double-blind, placebo-controlled Phase 2/3 studies to evaluate the efficacy, safety and tolerability of BHV-7000 in patients with focal onset epilepsy.

We are recruiting people aged 18-75 who have been diagnosed with focal onset epilepsy for at least one year, have at least four or more observable focal seizures every 28 days, are considered to have drug resistant epilepsy, have been unsuccessful with at least two anti-seizure medications (ASMs) and are currently on a stable dose of at least one to three ASMs.

People enrolled in the studies will take BHV-7000 or placebo once daily. Patients will have one baseline in-person clinic visit and then regular in-person monitoring at the trial site.

The primary objective of the study is to determine the change from baseline in 28-day average seizure frequency.

For more information about the trials and to find a study site, visit epilepsyresearchstudy.com.

How does BHV-7000 differ from other antiseizure medications? What are some of its advantages?

The investigational treatment BHV-7000 works on a part of the nerve cells in the brain called potassium channels, which help balance the electrical activity in the brain. Activating potassium channels can stabilize overactive brain activity responsible for seizures.

The proposed mechanism of action of BHV-7000 is different from other similar drugs in that it focuses on the potassium channel and avoids a different channel called GABAA, which may help it be better tolerated.

Early research has shown BHV-7000 to be successful in treating seizures in animal models of epilepsy. Our most recent research in healthy volunteers so far has found BHV-7000 to be well-tolerated, not causing some of the typical nervous system adverse effects like sleepiness seen with many other anti-seizure medications.

What are some of the challenges with treating and controlling focal onset epilepsy?

Focal seizures affect up to ∼61% of people with epilepsy.¹ They begin on one side of the brain and may cause changes in awareness, behavior, or sensation, or abnormal movements often on just one side of the body.²

There is an urgent need for more research, better treatments, and more support for people with epilepsy.3 Despite the advent of new treatments for epilepsy, a high unmet need remains unaddressed due to the tolerability of currently approved treatments and the fact that up to 40% of people with epilepsy are drug-resistant.¹

People with epilepsy tend to have more physical problems (such as fractures and bruising from injuries related to seizures), as well as higher rates of psychological conditions, including anxiety and depression.² The risk of premature death in people with epilepsy is up to three times higher than for the general population.⁴

Are there any data readouts or expected completion date for this study?

We do not have timing available to share for the data readouts or completion of the study.

References
1. Ioannou P, Foster DL, Sander JW, et al. The burden of epilepsy and unmet need in people with focal seizures. Brain Behav. 2022 Sep; 12(9):e2589.
2. US Centers for Disease Control and Prevention (CDC). Types of Seizures. Available at https://www.cdc.gov/epilepsy/about/types-of-seizures.html. Accessed June 13, 2024.
3. Epilepsy Foundation. Facts and Statistics About Epilepsy. Available at https://www.epilepsy.com/what-is-epilepsy/statistics#:~:text=There%20is%20still%20an%20urgent,disease%2C%20and%20traumatic%20brain%20injury. Accessed June 13, 2024.
4. World Health Organization. Epilepsy. Available at https://www.who.int/news-room/fact-sheets/detail/epilepsy. Accessed June 6, 2024.