SUMMIT, N.J.—Engage Therapeutics, Inc. has announced that data from a Phase 2a study of Staccato alprazolam to suppress seizures in patients with epilepsy were published in Epilepsia.
Staccato alprazolam is a single-use, investigational epileptic seizure rescue therapy that combines Staccato delivery technology with alprazolam, both of which have been approved separately for unrelated indications by the U.S. Food and Drug Administration. Alprazolam is a well-known and highly characterized benzodiazepine typically prescribed for the treatment of anxiety disorders. The Staccato system aerosolizes a drug and, via inhalation, delivers it deep into the lung for rapid systemic exposure.
This proof-of-concept study demonstrated that Staccato alprazolam delivered the drug deep into to the lung and rapidly suppressed seizure or epileptiform activity in five photosensitive patients with epilepsy. The paper, entitled, “Inhaled Alprazolam Rapidly Suppresses Epileptic Activity in Photosensitive Participants,” was published online ahead of print on July 7 in Epilepsia, the journal of the International League Against Epilepsy.
“The greater epilepsy community of patients, families and health care providers knows full well that there is an urgent need for acute rescue options to reduce or even halt seizure activity,” said lead author Jaqueline A. French, M.D., the study’s principal investigator, professor in the department of Neurology at NYU Langone Health’s Comprehensive Epilepsy Center, and founder/director of the Epilepsy Study Consortium. “The encouraging data from this Phase 2a study served as the foundation for advancing Staccato alprazolam in the clinic as a potential rescue medication for the acute treatment of seizures.”
The study referenced in the Epilepsia paper demonstrated that three doses of Staccato alprazolam (0.5 mg, 1.0 mg, and 2.0 mg) rapidly suppressed epileptiform activity in photosensitive participants with epilepsy. The primary endpoint of the study was the change in standardized photosensitivity range (SPR) in participants receiving each dose of Staccato alprazolam.
“Data from this proof‐of‐concept study showed that treatment with Staccato alprazolam was effective in reducing the SPR at the earliest measurable time point (2 minutes). Of note, given the time required to perform photic stimulation, an effect at times < 2 minutes could not be evaluated,” the article notes. “Due to this limitation, it is possible that the onset of effect could have occurred earlier.”
The effect was sustained through four hours for the 0.5 mg dose, and six hours for the 1.0 and 2.0 mg doses. Magnitude and duration of sedation and sleepiness were dose related and more prominent with higher doses. Peak plasma concentrations following administration were achieved following inhalation within minutes, and the rapid onset of pharmacodynamic effects of somnolence and sedation were observed.
The article also points out that “it is unclear whether the ability to suppress photoepileptiform activity will translate into suppression of ongoing seizure activity. This proof‐of‐concept study did show that the Staccato system delivered a sufficient quantity of alprazolam to suppress epileptiform activity at an early time point. The rapidity of onset may suggest the ability to quickly suppress ongoing clusters of seizure activity, such as myoclonus, that may otherwise evolve into a generalized tonic‐clonic convulsion.”
“Moreover, in participants with a prolonged aura or focal seizure, a treatment that takes effect within no more than 2 minutes from administration may be able to shorten a seizure that is already underway,” continues the article. “These opportunities and the feasibility of self‐administration will need to be explored in further efficacy studies.”
Staccato alprazolam was generally well tolerated, with a safety profile similar to what has been reported for oral alprazolam or Staccato alprazolam for other indications. No participants in this study experienced any severe or serious adverse events. Four of five participants experienced at least one adverse event during the study, but all were mild or moderate in intensity.
Engage Therapeutics is now enrolling up to 123 patients in the multi-center StATES study (Staccato Alprazolam Terminates Epileptic Seizures), a Phase 2b trial designed to evaluate the safety, efficacy and usability of Staccato alprazolam in subjects with epilepsy who have a predictable seizure pattern. The StATES study is being conducted at approximately 50 trial sites in the United States, Australia and Jamaica.