Greg Mayes is the president, CEO, and founder of Engage Therapeutics, founded in 2017 to clinically develop and progress a product called staccato alprazolam, which had just emerged from phase 2A testing. Staccato alprazolam has the opportunity to become the first FDA-approved inhaler therapy to abort an active seizure.
1. What is your background? What led you to Engage Therapeutics?
I’ve been a pharma executive for close to 20 years. I started out on the legal side with a large law firm doing life science transactions, then moved into AstraZeneca. Slowly I’ve been working toward smaller, more biotech-oriented environments. My experience in the pharmaceutical industry was primarily in oncology; however, when my son was diagnosed with epilepsy, I really wanted to make a difference in that community.
I founded Engage Therapeutics in 2017 based upon a recommendation from a group of epileptologists at the NYU Comprehensive Center for Epilepsy. The group is called FACES, which stands for Finding a Cure for Epilepsy and Seizures. Dr. Jackie French was the one who approached me about the product, and she and Dr. Orin Divinsky have been instrumental in staccato alprazolam’s development.
2. So you have a personal connection to epilepsy?
Yes, my son was diagnosed in 2014. Obviously it was a big shock to us, and it really changed the course of our family—where we thought we were headed. One morning, my son was basically eating cereal and next thing we know his head was in the cereal bowl and we weren’t sure what was going on, but recognized it to be some kind of seizure activity that required an immediate trip to the emergency room. Since then we’ve become very involved in the epilepsy community, and this opportunity with staccato alprazolam is my way to give back and make a difference with a new therapeutic option that does not currently exist.
3. How exactly does the product work?
The product works like an EpiPen. With that device, when a person has an allergic reaction, they can inject themselves quickly and put the allergic reaction to bed. However, this product will not require an injection; it is an inhaler, which takes just one small, natural breath. Within two minutes as observed in the clinical trials, seizure activity was terminated, and the individuals in the phase 2A trial remained seizure-free for several hours thereafter.
4. Can you elaborate on the Phase 2A trial?
Yes, when I found this opportunity, the product had just emerged from a Phase 2A trial, where five photosensitive epilepsy patients were evaluated with the product over three dosing ranges. These patients were able to have seizures artificially induced and then the inhaler was administered. Amongst these patients, there was an 80% response rate to immediate seizure termination. There was evidence of seizure cessation within 30 seconds, and the drug reached T-max within two minutes. So investigators saw something that has never been seen to date: the rapid termination of an ongoing and evolving seizure situation. And the patients remained seizure-free for several hours thereafter.
5. But aren’t there already other rescue medications available?
The primary approved “rescue medication” is rectally administered and has a slow onset of action—10-15 minutes. Because of the social awkwardness of administering in a public space, physicians simply won’t prescribe the existing product for adults; it’s almost strictly used with kids. There are also oral medications, but these are not always effective for the simple reason that many individuals cannot swallow a pill when a seizure is underway.
6. You’ve claimed that this therapy benefits patients in the short and long term. Can you explain?
Yes, every seizure puts a person out of commission for 24-48 hours, because it’s like running a marathon without being trained for it— you’re exhausted, you’re wiped out, your body needs to essentially reset after a seizure. But beyond the 24-48 hours, there is a whole host of physical and mental baggage that comes with a seizure. And your brain can only tolerate so much of this before you really start to see signs of cognitive impairment. If this product can stop seizures that we know are patterned to evolve, that would be a huge benefit because it would prevent the 24-48 hour post-seizure activity and improve the overall prognosis for the patient in terms of their wellbeing.
7. Seizure detection technologies are currently being developed. Could the inhaler work in tandem with those technologies?
Yes. Currently, individuals rely on physical clues to know when to use the inhaler, but that may change. An iPhone, iWatch or some other technology that’s being developed could warn the patient or caregiver in time that a seizure is coming on. This would allow for someone to have concrete data that says, based upon brain wave activity, a seizure is coming in 2-3 minutes. With this information and the inhaler, the person could abort the seizure prior to it even starting.
8. What will it take for this product to come to market?
Currently, Engage Therapeutics is enrolling patients in a Phase 2b study to test staccato alprazolam. Because it is important to ensure in a clinical trial setting that our drug is having the right effect on patients, we have to select a narrow subset of patients. Qualified patients have uncontrolled epilepsy with predictable, weekly, longer seizures (lasting 3-5 minutes). By predictable, I mean we’re looking for people who feel their seizure activity coming on—whether that’s smelling burnt rubber, seeing flashing lights, experiencing gastric upset. These patients would take one breath of the inhaler, and we would measure the impact on seizure activity.
As soon as we get 100 patients, we’ll be able to collect this data and go to the FDA. Because the therapy will be viewed as an unmet medical need, we will probably request an accelerated regulatory review pathway for the product. Then we’d commence a pivotal Phase 3 study, which would focus on the usability of the product in an at-home environment. This round wouldn’t require weekly seizures; we could have patients who have seizures over a 2-3 month period.
9. How can interested patients determine if they qualify for the current study?
They can start by filling out a recruitment form here.
10. Assuming all goes well, what’s next for you and Engage Therapeutics?
Once we move this product forward, I want to stay involved with the epilepsy community. I want to see what other options and opportunities are out there. The way our family has responded to the illness is really just to fight back. So whatever we do will be towards that end—making a difference for the many individuals like our son who live with this condition.