Biohaven Refines Epilepsy Trial Design With Patient-Centric Focus
A conversation with Jason T. Lerner, MD, medical director, R&D and clinical lead, Biohaven

Designing a clinical trial that meets patients’ medical needs and better enables their participation (and satisfaction) in clinical research is the hallmark of patient centricity. These trials are often touted and frequently discussed in theory. To understand how to bring the theoretical into reality, Clinical Leader talked with Biohaven’s Jason T. Lerner, MD, who has relied on his wife and his decades' worth of treating or working with epilepsy patients to create the company’s latest anti-seizure medication trial amenable to both patients and regulators.
You indicated your interest in treating epilepsy was informed in part by your wife's diagnosis. What from your and her experience has allowed you to develop trials that meet patients’ needs?
When I was in medical school, I met my wife who had been diagnosed with epilepsy when she was a teenager. During my child neurology residency, we lived in New York City where she ran support groups with teens with epilepsy. At the time, I was in neurology, still deciding on a subspecialty, and I had the opportunity to observe some of these support groups. Listening to the struggles these kids were having — things like stigma associated with epilepsy, not being able to drive, and difficulties with friends and parents — I realized that this population needed a lot of help and guidance, and that influenced me to specialize in epilepsy.
At Biohaven, the BHV-7000 compound that we're developing for epilepsy has shown minimal adverse effects in early studies. Quality of life in people with epilepsy is now discussed more frequently but for a long time it wasn't the focus which was primarily stopping seizures. While that is essential, we need to make sure we are not negatively impacting quality of life and hopefully making improvements. When I think about developing trials, I wonder, “What are the difficulties that some patients with epilepsy have in participating in trials?”
One is travel, particularly getting to sites for visits with the research team. We also know that studies take a lot of additional visits compared to how often someone would normally see their doctor in a year. One thing we are doing is providing transportation such as taxis or Ubers to help with travel. We also tried to reduce site visits and even offered a couple of virtual visits. We’re also looking at completing more of the trial at the home. I'm hoping to look at that more, really trying to make it more convenient and easier for patients to be able to gain the benefits of participating in trials.
You mentioned integrating at-home visits in future trials. What are some procedures that can be done within the home?
Nearly anything can be done at home these days. Nurses can draw blood, interview patients and perform exams. Now services such as EEGs and ECGs and eye exams can be done in the home. There is a lot to organize and there are many moving parts, but it's the direction we think trials need to go.
Along those lines, are you using any digital health tools now or planning to do so in future trials?
We have implemented digital diaries, using a patient’s phone or a device we provide, and ask patients each day to check in and answer, “Did you have a seizure today? Yes or no? If you did, what type is it?” It's really as simple as that. Past diaries included the timing and duration, which makes it complicated and burdensome for the patients. We wanted to eliminate a lot of that, while still having accurate seizure counts.
Realistically, most of us are going to forget days here and there. The FDA has now agreed to give patients a seven-day look-back period. And we're observing whether people are reporting and if they haven't reported in four or five days, someone from the site reaches out and encourages them to submit.
What led to the decision to remove seizure time and duration from the diary?
It would be interesting to see how long these seizures last and their severity. The problem is they're really difficult to quantify. For someone to say, especially when they’re having the seizure themselves, that a seizure lasted 30 seconds versus a minute and 30 seconds without someone there watching them, is just not realistic. And how much can you really make out of that? We debated that a lot but felt having patients do all this extra work, we didn't think it was going to be worth it.
In a way, I think you've addressed a few patient recruitment and retention challenges by collecting what sounds like only the data you need for the trial endpoints and nothing extra.
I work with our statisticians a lot and, as an epileptologist, especially a pediatric epileptologist, there are so many interesting, exciting things to look at. But they had to bring me back down to earth, asking, “Is that realistic? Is it worth having the patients do those extra steps? Is the data going to be good?” We had to sit down and decide what's really important, what's going to help the most.
Your career has often involved adolescent patients. This particular trial is an adult population. Is there anything that helped you with your work with adolescents translate into an adult population, or is it distinctly different?
It's really difficult for teens with a variety of different medical illnesses, not only epilepsy, to transition from a pediatric epileptologist to an adult epileptologist. You've developed such a bond with a physician and all of a sudden, you're 18 or 21 and now you have to go to a different doctor. It's unfortunate, but that’s how things are these days. One thing I focus on is quality of life when transitioning patients to adult physicians — being able to develop a really good history to pass on to the adult epileptologist is key.
The epilepsy is important, but there are comorbidities associated with it. About 30%-40% of people with epilepsy have depression, anxiety, learning disorders, and sleep disorders, and some of these have a greater impact on quality of life than seizures themselves. I like to dig into that before they move on to adult physicians. That is another thing that we're excited by with BHV-7000 — while it has the potential to be a great anti-seizure medication, it also has the potential to be an antidepressant and a mood stabilizer for bipolar disorder. We're running parallel trials in both. The hope is that we could have a medication that's efficacious for epilepsy with a low adverse effect profile that's also efficacious in depression. So, maybe we can treat someone with comorbid depression and epilepsy with one medication rather than having them on two or three medications.
Talking about some of those current anti-seizure medications, why aren't they good enough?
Over the last 10 to 15 years, we've had a significant influx of new anti-seizure medications. However, 30% or so of patients with epilepsy still have seizures — even with receptive surgeries, devices like RNS, DBS and VNS, special diets like the ketogenic diet. I’ve used all of the above, but there's still a subset of the population for which you can't completely control the seizures.
BHV-7000 is a potassium channel activator, which is different than any other anti-seizure medication in the market, which are frequently GABA-related or sodium channel medications. So far, we haven't seen much of an improvement in seizure freedom and seizure frequency. And some older medications which may be a great medication for efficacy, has a laundry list of adverse effects that have an impact on people's quality of life. The newer medications have improved on that to a degree but are still associated with a lot of side effects like somnolence and dizziness. In our early Phase 1 multiple ascending dose studies, not a single subject reported somnolence.
We’re looking closely at any adverse effects (AEs). And once the study's over, we’ll be looking at how often subjects experienced AEs and whether, when the double-blind is opened, they were on actual treatment versus placebo, because there is a fairly high placebo effect in anti-seizure medication trials. There are some medications that have come out and the studies have shown high rates of AEs, but many of these could be observed in the placebo group.
Looking ahead, whether it's for BHV 7000 or just the field in general, what are some of the things you are looking forward to or excited about for the treatment of epilepsy?
We have two trials for focal epilepsy where seizures come from a specific focus in the brain and one trial for idiopathic generalized epilepsy where seizures originate from the whole brain at once. The trial for idiopathic generalized epilepsy trial has a unique design to address safety in antiseizure medication trials. We know that patients with epilepsy, especially those who have generalized tonic-clonic seizures, have a high rate of SUDEP, which is sudden unexpected death in epilepsy. There was a paper not long ago that looked at many epilepsy trials, and what they found was the rates of SUDEP were higher in subjects who were in the placebo arm or subjects who were in the treatment arm and the treatment wasn’t working for them compared to active treatment. So, you want these patients in the placebo arm or poorly treated arm for as short a period as possible. To achieve this, we included a retrospective observation phase (avoids 12 weeks without potential new treatment) and then a double-blind phase where patients may be on placebo or active treatment for 24 weeks. However, after a patient has their second day with a generalized tonic-clonic seizure, they can move directly to open-label during which they will be on active treatment without having to stay the entire 24 weeks while still having seizures. If they are doing well and not having seizures in the double blind phase they would continue for the whole 24 weeks. This is called a time-to-event trial design, which we feel is a safer trial design overall.
In the future, I believe all generalized epilepsy trials are going to be done this way because of the significant safety factor. And we're hoping maybe even focal trials will be. I think this trial's only been done like this once and it was a Phase 4 trial with a drug that was already approved, and this is the first time anyone's doing it for an approval for a new drug.
About The Expert:
Jason T. Lerner, MD is a board-certified pediatric neurologist and epileptologist and was a clinical professor at the University of California, Los Angeles before joining Biohaven in the spring of 2022. At UCLA, Dr. Lerner was the associate child neurology division chief and the director of the Adolescent Epilepsy Center at UCLA. He held many leadership positions including director of the Pediatric Neurophysiology Lab and director of the Child Neurology Residency Program and contributed to numerous clinical trials. He has published more than 35 articles and book chapters in journals such as “Epilepsia,” “Neurology,” and the “Journal of Clinical Neurophysiology.” In his current role at Biohaven, Dr. Lerner is a medical director and clinical lead of the BHV-7000 development program in epilepsy.
After graduating from the New Jersey Medical School in 2000, Dr. Lerner completed a residency in pediatrics at the Penn State Health, Milton S. Hershey Medical Center, a residency in child neurology at the Albert Einstein College of Medicine, Montefiore Medical Center, and a fellowship in pediatric clinical neurophysiology at UCLA.