Phase 2A Clinical Data

Engage Therapeutics is developing Staccato alprazolam, an easy to use, hand-held inhaler that could be the First rescue treatment of its kind with the aim to stop epileptic seizure activity. In a phase 2a proof of concept trial, Staccato alprazolam has been shown to abort seizure-like activity in less than two minutes. The therapy, which is now being evaluated in a phase 2b study, combines the FDA-approved Staccato delivery technology with alprazolam, a well-known benzodiazepine that has potent and effective anti-epileptic properties, to rapidly terminate seizure activity once it has begun. If approved, this would be the first product approved for such an indication. Engage Therapeutics is using the 505(b)(2) regulatory pathway to develop and seek approval for Staccato alprazolam.

Why Staccato and Alprazolam?


Alprazolam, which has decades of safety data supporting its continued commercial availability, has shown anti-epileptic activity, and the Staccato system, achieves an unprecedented speed of onset. Staccato alprazolam is exclusively licensed from Alexza Pharmaceuticals, Inc. Staccato’s easy-to-use aerosol delivery technology activates a heating element to vaporize alprazolam which rapidly delivers the drug and reaches Tmax in just two minutes – and has been shown to effectively terminate seizure activity in two minutes. When patients draw a normal breath through the Staccato system, the substrate surface instantaneously heats to create a condensation aerosol. The patient inhales particles ideally sized for systemic delivery of excipient free drug down into the narrower, more vascularized tissue of the deep lung, allowing fast and more complete absorption into the bloodstream. The Staccato system is the only technology on the market that non-invasively delivers a drug as quickly as an IV and has a bioavailability greater than ninety percent. This innovation in aerosol delivery has the potential to revolutionize the treatment of epileptic seizure activity by stopping it soon after it starts.

Fulfilling an Unmet Need


Epilepsy is a condition that causes seizures and is the fourth most common neurological problem in the world according to the Epilepsy Foundation. At least three million patients in the United States are living with epilepsy, and one-third of those patients have uncontrolled seizures because no available treatment works for them. Approximately twenty percent of those patients have a seizure pattern that they can predict and are in need of a rescue treatment to stop on-going seizure activity before their seizure progresses. Currently, there are no approved products or products in development that can rapidly stop an active seizure in the outpatient setting.

Safety is a chief concern for patients with epilepsy who experience prolonged or on-going seizure activity. Prolonged or recurrent seizure activity may result in serious injury or death, that correlates directly with seizure duration. Stopping seizure activity early before it has the opportunity to progress may allow patients to continue on with their normal activities and help prevent neurological damage.

Benzodiazepines are considered to be medications of first choice for the treatment of acute seizures. Clinical advantages of benzodiazepines include relatively rapid onset of action, high efficacy and minimal toxicity. The onset of action plays a significant role in reducing the time needed to treat seizures and reducing the likelihood of damage to the central nervous system.

The potential benefits of Engage’s Therapeutics’ candidate therapy include a fast delivery to the blood stream, comparable to IV administration. and the ease of use in the outpatient setting. Staccato alprazolam could be administered immediately after seizure activity is recognized.

Engage wants to redefine what it means to live with epilepsy and to provide a viable solution for patients with the only product on the market that delivers medicine as fast as IV, but non-invasively and at arms’ length to terminate seizure activity.