Improving Developmental Epileptic Encephalopathy Treatment With Soticlestat

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

Eric Segal, MD

Recent data show that treatment with soticlestat was associated with a progressively improving median seizure reduction of up to 90% in patients with developmental epileptic encephalopathies. Although the ENDYMION open-label extension included only 7 patients, the data are promising in these rare conditions with few treatments.

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, has been involved in the clinical development of the first-in-class cholesterol 24-hydroxylase (CH24H) inhibitor. As such, NeurologyLive reached out to Segal to glean some of his insight into the therapy’s efficacy.

Through 25 to 36 weeks, 6 patients had experienced median seizure frequency reductions of 84%, increasing to 90% in 4 patients through weeks 37 to 48. In addition, the longest seizure-free durations experienced by 2 different patients were 264 consecutive days and 150 consecutive days, respectively. Segal provided context to these findings to explain how soticlestat can address challenges in developmental epileptic encephalopathies, as well as what may be next in its advancement.

NeurologyLive: Are there any challenges outside of failure on other therapy that that this is potentially addressing? What sort of advantages, outside of its efficacy, does this offer clinicians?

Eric Segal, MD: Any first-in-class medication is something that we think about for these refractory epilepsies where patients tend to be on polypharmacy. We want to bring in a new therapy that works completely different than what they're currently taking. We don't have so many therapies that would fit into a rational polypharmacy, but anything that will work completely different and we can attack the epilepsy disorder from a different angle or perspective is very helpful. I think it's very interesting to see further agents that work on the glutamate system, especially on the NMDA system, as this medication does. Those are probably the times that a clinician will start thinking about this kind of medication because it works completely differently than the other ones that we have available. It may be an excellent complement to these other therapies.

Additionally, tolerability is a big deal. To have such a significant seizure reduction, a least in a small group of patients, and have a very good track record in terms of the adverse events and the most common adverse events. That is very helpful. When we're looking to add medications, we want to make sure that it's not going to exacerbate any other conditions that patients may have.

What’s the next step in the clinical development of soticlestat?

The sense I have is that there's really 4 different disease states that this drug is being studied in: Lennox-Gastaut and Dravet, 15q duplication syndrome, as well as CDKLl5 deficiency disorder. These, with the advances in genetics and genetic testing, as well as the increase in the use of genetic testing not only in the pediatric epilepsy world but especially in the adult epilepsy space, my hope is that we can use this therapy and others to guide us into more precision medicine, and to be more precise with the therapies that we’re administering for our patients. My hope is that with the increase in medications that have an orphan drug designation, that will push the clinicians into to do even more testing than we already do now to better understand the etiology of some of our non-acquired epilepsies. This way, we can be more precise in terms of the therapies that we're giving, and also have a better understanding of the prognosis for these patients and what to possibly expect in the future.

This kind of therapy, first of all, can be very effective and positive in terms of the efficacy and the tolerability of what we know so far. Since these therapies with orphan drug designation are available to specific etiologies, a possibly unintentional, additional benefit may be a further genetic investigation for certain refractory patients that may benefit from these unique compounds. By better understanding the etiology of our patients’ epilepsies, we may be able to shed even more light on their prognosis and other therapies that may be available to them.

Is there anything you’d like to add or mention about soticlestat?

I think the data that's it that we have available, that shows, you know, sees your reductions that are pushed into the 60-70th percentile is significant. And I am very curious, just to see how this works in a larger group of patients. With some of these rare disorders, I think we'll have a lot more understanding about how I think we'll have a lot better understanding of what our expectations should be for this particular therapy as we have a higher number of studies, releasing their data.

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.