Transforming Rapid Seizure Termination Care with STACCATO Alprazolam

• STACCATO alprazolam, an experimental drug-device amalgamation, heralds a notable progression in epilepsy therapy. Harnessing the STACCATO delivery technology signifies a paradigm shift by facilitating swift seizure cessation within a mere 90 seconds. This achievement is made possible through a handheld inhaler device meticulously crafted for seamless administration, promising enhanced efficacy and ease of use. 
• The analysis presented by UCB Pharma highlighted STACCATO alprazolam’s potential to revolutionize seizure management, as evidenced by its favorable pharmacokinetic and tolerability outcomes observed in adolescents with epilepsy.

While anti-seizure medications effectively control epilepsy by decreasing seizure frequency and intensity, they aren’t formulated for immediate seizure cessation. Additionally, research showing the ability to stop ongoing seizures when administered by patients or caregivers at the first signs of seizure onset is lacking. Consequently, there’s a pressing demand for medications capable of promptly and reliably terminating seizures within seconds to minutes, particularly for emergencies. These medications should achieve rapid absorption into the bloodstream without necessitating intravenous access, particularly in the treatment of Rapid Epileptic Seizure Termination (REST) epilepsy.

At the recently concluded, 2024 American Academy of Neurology (AAN) Annual Meeting, UCB Pharma unveiled findings elucidating advancements in its extensive neurology portfolio, featuring their drug candidate STACCATO alprazolam. The presentation underscored the company’s dedication to patients and the momentum of UCB’s epilepsy portfolio. Specifically, they shared outcomes from a study investigating the pharmacokinetics and tolerability of a single dose of STACCATO alprazolam in adolescents with epilepsy, along with a population pharmacokinetic analysis aimed at informing dose selection in adolescent patients.

In a Phase I study involving adolescents aged 12‒17 years with various forms of epilepsy, the pharmacokinetics and tolerability of a single dose of STACCATO alprazolam were evaluated using systemic delivery via inhalation. Following the administration of 2mg of STACCATO alprazolam, patients exhibited generally rapid absorption, with a median time to maximum concentration (Tmax) of 10.5 minutes. The subsequent elimination was characterized by a half-life of 7.6 hours, although there was notable variability in absorption among individuals. While no serious adverse events were reported, mild to moderate events such as dysgeusia, somnolence, dizziness, cough, and hiccups were observed predominantly in patients weighing ≥50kg. Exposure estimates from simulations suggested comparable exposure (AUC) among adolescents receiving adult doses of 2mg alprazolam, with slightly increased maximum concentration (Cmax) observed in those with lower body weight. 

The findings indicated favorable tolerability of STACCATO alprazolam 2mg, with body weight showing no clinically significant impact on pharmacokinetic and safety parameters. Model-based analyses suggested that an adult alprazolam dose of 2mg could be safely administered to adolescents without adjustment. This addresses a critical unmet need for convenient alprazolam delivery, enabling individuals with epilepsy and their caregivers to effectively manage active seizures with a single breath. The system facilitates rapid vaporization of alprazolam to generate an aerosol, designed for deep lung delivery, thus ensuring swift systemic effects.

Conclusion: With its innovative design, STACCATO alprazolam empowers patients or caregivers to administer treatment in an outpatient setting, meeting the urgent demand for swift intervention.