NeuroVoices: Eric Segal, MD, on Real World Use of Diazepam Nasal Spray

Eric Segal, MD

At the American Epilepsy Society Virtual Meeting, December 4–8, 2020, Eric Segal, MD, presented interim data from a long-term phase 3 study of diazepam nasal spray (Valtoco; Neurelis) which demonstrated that the treatment remains effective in reducing the percentage of seizures regardless of concomitant use of benzodiazepines. Segal and colleagues found that the percentage of seizure episodes using a single dose of diazepam nasal spray was similar for those with concomitant benzodiazepines (90.5%) compared to those without (92.4%).

Intranasal diazepam was approved by the FDA for the treatment of acute, intermittent, stereotypic episodes of frequent seizure activity, otherwise known as seizure clusters, in January 2020. Segal, director of pediatric epilepsy, HMH Hackensack University Medical Center, claims his research is a real-world study which debunks any of the “honeymoon” thoughts that are associated with a diazepam, who’s shelf life is still relatively new.

Segal sat down with NeurologyLive on a new segment of NeuroVoices to provide background on the study, takeaways from the results observed, and how the research can be used in a clinical setting.

NeurologyLive: Can you provide further details about your study? What is its significance?

Eric Segal, MD: Up until recently—less than a year ago—the only emergency medication that we had for acute repetitive seizures was rectal diazepam (Diastat; Bausch Health). With the ability of nasal diazepam, the concerns have shifted to: if we use nasal benzodiazepine, how does that affect a patient who’s already taking a benzodiazepine? People can take long-acting benzodiazepines orally in addition to getting it emergently. The 2 questions were: do the patients who take benzodiazepines already have a tolerance to taking benzodiazepines, and therefore, will it work emergently? And the other being, would there be any problems by giving more benzodiazepines on top of benzodiazepines already taken? With that in mind, we found that there wasn’t a significant tolerance. Patients typically only needed 1 spray to break up the seizure or seizure cluster. Similarly, there was no real increased significance and adverse effects when observing the benzodiazepine concomitant group versus the non-concomitant group.

We did see patients who were taking daily benzodiazepines typically have more seizures while receiving more rescue sprays in a month, but I don’t think that is related to the medication. People who are taking daily benzodiazepines to prevent seizures generally have a higher seizure burden. The take home messages from the study are that diazepam nasal spray doesn’t appear to have a significant tolerance to benzodiazepines and that it may be used at the prescribed doses urgently. On top of that, there was no increased adverse effects in that population.

Do you believe your results may change clinicians’ perspective on prescribing to their patients? Could it possibly lead to more singular prescriptions of diazepam nasal spray?

This study, in addition to a few others regarding this treatment, should serve as an opportunity to change and improve patient practice. There are a few reasons why. First, is that we see there’s no significant tolerance. In my personal clinical practice when it came to using Diastat, which was the only thing we had previously, we had to give a higher than prescribed doses for it to work because these patients would be taking other antiseizure benzodiazepines. We don’t see the need to do that in this particular study. For those with difficult to treat epilepsies on multiple benzodiazepines, we see that this rescue medication works, and it works at the prescribed dose that you would give to someone who’s not taking daily benzodiazepines. Those are the reasons why it would change practice.

The lack of significant changes in adverse effects among the 2 populations just gives further reassurance to the clinician that this is a safe treatment to give. This is really a game changer for our independent patients. In general, rectal medicines are usually given between the 2 to 5 years age group. Most adults, and in fact many children, don’t want to have their pants pulled down to get an emergency medication, for the obvious social reasons. Now we have something that’s a bit more socially acceptable, is superior to Diastat because of the mechanism of delivery, and doesn’t create any further significant adverse effects in this patient population. On top of that, there’s no tolerance effect. There are all reasons why I think this is probably a more widely accepted treatment than what we’ve been using previously.

What is next for this drug, considering it has already received FDA approval?

There are 2 different directions for clinical trials for this particular medication. One is to see if we can open up the age indication more. Right now, it’s for ages 6 years and up. There’s a significant pediatric population between the ages of 2 and 5 years that could really benefit from this. I would imagine that the company would want to study that a little more closely. One of the questions that comes up is: how well does the medication work in terms of breaking up seizure clusters? There’s 1 trial that comes to mind. The way the clinical trial was enrolled, it didn’t have to prove efficacy—they only had to prove that the concentration of diazepam that was in the blood was the same in patients who receive Diastat. They compared the Diastat and Valtoco to patients who were and were not having seizures. The numbers turned out to be essentially the same when compared with Diastat. What was remarkable was that the amount of variability decreased. There was a less of a difference in bioavailability, meaning that you were assured you had the consistent dosing every time you received Valtoco. That’s great, but the next step is to show that administering this particular therapy is effective by looking at the timing of seizures and the timing of resolution to the clusters.

When can we expect the full results of the study? What more are you hoping to accomplish?

There are a few publications that have been submitted to several journals using this data set and others. With this particular data set, the end goal is to show real-world experience using this relatively new medication. It was approved in March, so clinicians can now see that this is not just a drug with a honeymoon effect, but actually a medication that has real staying power and persistence throughout the course of a person’s life with epilepsy.

Transcript edited for clarity.

For more coverage of AES 2020, click here.

REFERENCE

Segal E, Tarquinio D, Miller I, et al. Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: interim analysis from a phase 3, long-term, open-label safety study. Presented at AES 2020 Annual Meeting; December 4–8, 2020. Abstract 337.