Soticlestat Shows Promise for Developmental Epileptic Encephalopathies

Eric Segal, MD, director of pediatric epilepsy, Northeast Regional Epilepsy Group, and co-director of epileptology, Hackensack Meridian Health

Eric Segal, MD

Recently, Ovid Therapeutics announced that its phase 2 open-label extension study of soticlestat produced initial positive results, with data suggesting that the therapy is effective over the long-term in treating patients with rare developmental epileptic encephalopathies.

Ultimately, the highly selective first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H) was associated with seizure reduction over 48 weeks in a small cohort of 7 patients. The median seizure frequency reductions were 84% after 25 to 36 weeks (n = 6) and 90% after 37 to 48 weeks (n = 4) of treatment, with 2 patients experiencing seizure-free runs of 264 and 150 consecutive days, respectively. Additionally, the safety and tolerability of soticlestat, previously known as OV935/TAK935, was consistent with the observations from the phase 1b/2a trial.

Amit Rakhit, MD, MBA, Chief Medical Officer, Head of Research & Development, Ovid, said in a statement that the clinical development program of soticlestat in developmental epileptic encephalopathies is expected to read out data from the ARCADE and ELEKTRA studies in 2020.

To learn more about soticlestat and the latest data, NeurologyLive spoke with Eric Segal, MD, director, pediatric epilepsy, Northeast Regional Epilepsy Group, co-director, epileptology, Hackensack Meridian Health, and assistant professor of pediatrics and neurology, Hackensack Meridian School of Medicine. Segal, a trial investigator for soticlestat, provided insight into the clinical takeaways and the potential of the therapy.

NeurologyLive: What does the clinician community need to know about these data and about soticlestat in general?

Eric Segal, MD: The preliminary data that we've seen thus far is very exciting for a first-in-class mechanism. We have pretty significant positive efficacy results in a small group of adult patients who typically have pretty severe epilepsies and it was well tolerated. I think all those pieces are very interesting.

Obviously, we need to see how this therapy works in larger groups of patients. That's going to be the next big thing. What I found to be the most interesting about the data was not only the significant median seizure reduction but also how seizure reduction was sustained and improved the longer the patients took on the medication. A lot of times when we look at open-label extensions, we tend to see a significant drop out in the number of patients. There's a small number of patients to start with, but the majority of those patients stayed in the study and had improvements in seizure frequency going from week 1 through week 36. That is very unique.

Are there any other specific datapoints that make this therapy stand out or make this therapy unique in this space?

There are a few things. One is that the sustained efficacy in this group of patients is significant. Especially in a group of patients with epileptic encephalopathies who tend to try or have used, and unfortunately have failed, some of our most effective medications that are available. To have such a high seizure reduction rate that is sustained in a group of people that have failed what we would think of as our strongest or most efficacious medications, I think that is very significant.

Is there a particular rare epilepsy or subgroup in which soticlestat has significant potential?

The therapy is underway in study for Lennox-Gastaut syndrome and Dravet syndrome. I would say that a lot of these rare disorders can be very difficult to treat in clinical practice. I think for most clinicians, of the potential indicated epilepsies, Lennox-Gastaut syndrome is probably going to be where you find the greatest number of patients with a great need, and it's exciting to see that this therapy is being considered for that. I'm really interested in seeing that in all the genetic epilepsies that that's being tested in. But especially in Lennox-Gastaut, given that we have such a large LGS community of patients that definitely need better therapies than are what are currently available.

Transcript edited for clarity.

REFERENCE

Ovid Therapeutics Announces Positive Initial Data from Ongoing ENDYMION Open-Label Extension Trial of Soticlestat in People with Rare Epilepsies [press release]. New York, NY: Ovid Therapeutics; Published September 23, 2019. ovidrx.com/news-releases/news-release-details/ovid-therapeutics-announces-positive-initial-data-ongoing. Accessed October 17, 2019.