The director of epilepsy research and epilepsy clinical trials at NYU Langone Health’s Comprehensive Epilepsy Center spoke about the recent study findings from a trial of Staccato alprazolam.
Jaqueline French, MD
Engage Therapeutics recently announced that its recent phase 2 StATES study of its investigational abortive seizure treatment, Staccato alprazolam, had met its primary end point of a meaningful proportion of responders achieving rapid seizure activity cessation.
The treatment, which was evaluated in doses of 1 and 2 mg in a cohort of 116 patients, has shown not just a significant responder rate above 50% compared to placebo (P = .0392 for both doses), but a mean approximate onset of action for ceasing seizure activity of 30 seconds.
To find out more about what these data mean for the epilepsy community and how this treatment might fit into the treatment landscape, NeurologyLive spoke with investigator Jacqueline French, MD, professor of neurology, director of epilepsy research and epilepsy clinical trials, NYU Langone Health’s Comprehensive Epilepsy Center, and founder and director, Epilepsy Study Consortium.
Jacqueline French, MD: That it was positive in both the circumstance of patients having repeated seizures and the circumstance of patients having a long seizure because, particularly, although we have had other treatments for people with repeated seizures—albeit they do not work as quickly—we have had no treatments for people with long seizures. It's a horrible feeling to have the onset of a seizure, that you know is going to go on and on and maybe turn into a more serious seizure like a convulsion, and you're just sitting there powerless and not able to do anything about it. To give people something to do about it is a huge burden off of them. It’s a huge relief.
Additionally, when we went into it, we were a little worried that because you have to take a breath, as opposed to somebody spraying something in your nose, which you think of as relatively passive. The person actually has to take a breath, and if somebody was having a seizure with impaired awareness, we were worried that would impact on their ability to receive the drug. The very reassuring news is that patients who did have impaired awareness are still able to use the drug.
Any benzodiazepine is going to produce some sleepiness, but I was pleased that it seems that the patients were not reading it as significant sleepiness. And, it appeared that they went quickly back to feeling like they could do their activities.
Absolutely the time to action. For most of the rescue therapies that cross the mucous membrane, for example, the nasal therapies that have recently been approved and certainly the oral therapies, the rectal therapies—no matter what other way you try and get it into the body other than an intravenous line, you're talking about an average of 10 minutes, and in an oral form 20 minutes. There is a huge difference between 2 minutes, or even less than 2 minutes in many people's cases, versus 10 minutes. In the lifetime of a seizure, that's an eternity.
The intent is to go to the FDA with an indication for people who need rapid control of seizure activity, whether that's because they have a prolonged seizure or they're having repeated seizures. So if somebody has a single brief seizure and you don't expect another for 20 minutes, then it doesn't matter whether you give them rescue therapy that takes 10 minutes to work or even 20 minutes to work, as opposed to if you have a situation where somebody is having a prolonged seizure—as I said before—or they're having frequent recurrent seizures. If you need a rapid cessation of seizures, then this is going to be a better bet to do that. That’s how you differentiate who would need this therapy.
I would say that is not the broader intended audience at this point. It would be people for whom there is enough history to understand that there is likelihood of continued seizure activity that needs to be stopped again, in the short term.
There is an advantage to the form this is delivered in, though, because if you're in the middle of a job interview, putting something up your nose may not be something you want to do, but anybody can take out an inhaler and say, you have to excuse me, I just have to use my inhaler for a second. We had a very positive phase 2 and we're really looking forward to a phase 3 where we can really see what the benefit is to people who are in the community trying to deal with their epilepsy.
Transcript edited for clarity.
Engage Therapeutics Announces Phase 2b StATES Study of Staccato® Alprazolam for Seizure Cessation Meets Primary Endpoint [press release]. Summit, NJ: Engage Therapeutics; Published March 12, 2020. Accessed March 12, 2020. globenewswire.com/news-release/2020/03/12/1999155/0/en/Engage-Therapeutics-Announces-Phase-2b-StATES-Study-of-Staccato-Alprazolam-for-Seizure-Cessation-Meets-Primary-Endpoint.html.