Trying this at home: Bioxcel steps closer to an sNDA for Igalmi

Lee Landenberger

Hello, this is the Bioworld Insider podcast. I’m Lee Landenberger. I’m a BioWorld staff writer and I’m also the host of the Bioworld podcast. Thanks very much for joining me. I cover drug development for Bio World, and our guest today is Vimal Mehta. He’s the CEO of Bioxcel Therapeutics. Today, Bioxcel released phase three results for its sublingual film formulation of dexmedetomidine.

That’s for an acute treatment for agitation that’s associated with bipolar disorders or schizophrenia, and it’s for patients in a home setting. The study met its primary objective and Vimal is here to talk about the data. Vimal, thanks very much for joining me today.

Vimal Mehta

Thank you, Lee, for having me. My pleasure.

Lee

So can you tell me about the study results and hitting the primary objective? It’s a big day for this drug in the company.

Vimal

It is indeed. I think it’s a big day for the company as well as for the patients and their families and caregivers who will benefit from this. So this is our lead product is BXCL-501 that we are testing right now in the home setting. And those are the results be announced today. So our drug Igalmi has been approved for treatment of agitation in schizophrenia and bipolar, but it has a label under medical supervision, so it’s used in an institutional setting.

Now with these results, we believe, or we hope that we will be able to move this drug in the home setting. So the trial was set up that we will take lowest approved dose, 120microgram of Igalmi, which is already approved and marketed into the home setting. And we tested in 200 patients, 100 on placebo, 100 on the drug, one to one randomization, double blinded placebo controlled pivotal phase C trial.

And the primary endpoint or primary objective was safety because efficacy of 120microgram has been established in two pivotal phase C trials, prior trials, Serenity 1 and 2, that led to the approval into the Igalmi. So now our goal is that with this data in hand, where we have it has met the primary endpoint.

We will be able to put a package together to go to the SNDA for SND submission. And data looks very consistent. What we saw, the safety and tolerability of the drug in the NCARE setting or current approved label. There are no discontinuations due to the drug, no serious adverse events, no syncopes or fall.

Those are the things we wanted to assess in a home setting. So I would say overall data is extremely Compelling and it will be a good package for our SND submission.

Lee

So what’s the unmet need behind this?

Vimal

Unmet need is huge because there are no FDA approved treatments in the home setting for treatment of vegetation in schizophrenia, bipolar. So it’s very transformative for our program to be able to demonstrate its safety and tolerability. Think of the patient, these agitated patients who are in the home setting and they take our film to calm them.

They are already agitated and, and they need something because agitation can be mild, moderate and severe and it escalates very fast. So nothing is available. And these patients normally end up in using meditation, some illicit drugs, alcohol or some of the benzodiazepines and other things to calm themselves. And when they don’t work they end up in the emergency room or other institutional setting where our product is available.

So our product has 120 microgram and 180 microgram two doses depending on the patient severity and 120 will now become in a home setting. And the opportunity is really large. Initially we estimated 23 million episodes in the home setting. But now we are realizing it’s much bigger. Based on our clinical data, market research literature, it’s all coming together.

It may be opportunity, something like 57 to 77 million episodes. So we are very excited that it’s such a high end need. There is no FDA approved therapy and our product, if approved by the FDA will help all these patients and the family members.

Lee

Tell me about the drug’s mechanism and what it’s designed to do.

Vimal

It’s a very unique mechanism. It works through the locus cerelus in the brain and our drug is so potent that we had to put micro deposition on the film. So it’s a sublingual film where there are two dots. Basically. Drug was deposited so that as soon as it touches it immediately start dissolving the drug and it has a rapid onset of action.

The mechanism is it works through the locus ceruleus in the brain and there is a alpha 2 adrenergic receptors. So when patients have a like, you know, higher state of agitation, they start releasing norepinephrine in the brain. And our drug can very selectively block that, the release of the norepinephrine and then it reverses the cost and patients start feeling calming effect.

It’s a very unique mechanism and drug safety and tolerability. As you have seen today, what we announced is really good and we believe that it will have lots of patients and prevent lot of agitation episode from escalating or going into the emergency rooms.

Lee

So how do these study data tie in with your planned SNDA submission to expand Igalmi’ s label?

Vimal

Yes. So we have got an alignment with the FDA. What the sNDA package is needed and this trial, phase three pivotal trial is a very integral and important part of that package. In this we needed to show FDA that drug is safe to use in a home setting. Patients will self-administer when they have an agitation episode.

And I’m very pleased to announce that we collected the data for these 200 patient 20, 600 agitation episode in a 12 week period. So there are a lot of agitation happening and we saw that very large, vast majority of the patient completed the 12 week period. So that also tells that patients like or they need something to help them with their agitation.

So I believe that it’s a very unique opportunity and a novel mechanism and in terms of a sublingual thin film which is optimal for these patients to treat themselves. And we are very excited with today’s results. In addition, we have some exploratory objectives to show that when drug is given over a 12 week period then it stays effective.

Lee

So, Vimal, can you tell me how long does it take for the drug to take effect?

Vimal

So in our previous trial when we got the approval, it starts working pretty quickly. We have shown that it can have as rapid impact depending on what dose you use within 20 to 30 minutes.

Lee

Anything else you’d like to mention?

Vimal

What I like to mention is never ever a drug has been approved by the FDA in your home setting. And to my knowledge, never ever trial has been conducted in a very pragmatic environment which is a real world environment. All these patients were allowed to take their regular drugs or interventions what that helps them with their agitation and our drug was given on top of it.

And we are demonstrating the safety and some of the early signals that our drug maintains the benefit this patient. It’s quite interesting and we are very excited now to take next steps and like, you know, bring this drug to the patients.

Lee

Vimal, thanks for your time and insight.

Vimal

Thank you very much for having me here.

Lee

That’s the BioWorld Insider podcast for today. Thanks for joining me. Bioworld is a daily news service covering the development of therapeutics. So if you need to track the development of drugs, you can find us at bioworld.com.

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