FDA OKs Midazolam Nasal Spray (Nayzilam) for Seizure Clusters

Megan Brooks

Disclosures

May 20, 2019

The US Food and Drug Administration (FDA) has approved midazolam nasal spray (Nayzilam, UCB) for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in epilepsy patients aged 12 years or older.

It is estimated that more than 150,000 people in the United States with uncontrolled epilepsy experience seizure clusters, which can increase the risk for physical injury, neurologic damage, prolonged seizures, and status epilepticus if left untreated.

Midazolam nasal spray is the first and only FDA-approved nasal option for treating seizure clusters. It is packaged as a single-use treatment that can be carried with a patient and administered by persons who are not healthcare professionals.

"When a patient experiences seizure clusters, there is often significant impact on their overall quality of life, in addition to posing greater risks for increased emergency department–related hospitalizations and more serious seizure emergencies," Steven Chung, MD, executive director and program chair of the Neuroscience Institute and director of the epilepsy program at Banner–University Medical Center in Phoenix, Arizona, said in a company news release.

"Further, as a neurologist specializing in epilepsy, treating seizure clusters today presents a challenging barrier for many patients. The availability of a new treatment option, such as Nayzilam, has potential to help improve the lives of patients and their families by providing another option for rescue care," said Chung.

The effectiveness of midazolam nasal spray for the acute treatment of seizure clusters was established in a two-phase, randomized, double-blind, placebo-controlled trial. An open-label test-dose phase was followed by a comparative phase.

In the test-dose phase, tolerability was assessed in 292 patients who, in the absence of a seizure, received two 5-mg doses of midazolam nasal spray (10 mg total dosage) 10 minutes apart. Patients were excluded from participating in the comparative phase if they failed to meet predefined criteria regarding blood pressure, heart rate, sedation, electrocardiographic status, and peripheral oxygen saturation.

In the comparative phase, 201 patients underwent treatment for a single seizure cluster episode in an outpatient setting with either a blinded dose of midazolam nasal spray 5 mg (134 patients) or placebo (67 patients).

If seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of midazolam nasal spray 5 mg, to be used between 10 minutes and 6 hours after administration of the initial blinded dose of study drug.

A statistically significantly higher percentage of patients who were treated with midazolam nasal spray met the primary efficacy endpoint of treatment success, defined as termination of seizures within 10 minutes after the initial blinded dose of the medication and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of the medication, the company said.

Numerical differences in favor of midazolam nasal spray were observed on each of the components of the treatment success responder definition: termination of seizure(s) within 10 minutes after initial dose of the drug (80.6% vs 70.1%), and the absence of seizure recurrence between 10 minutes and 6 hours after the initial dose (58.2% vs 37.3%).

The study also evaluated the occurrence and time to next seizure after receiving the initial blinded dose of the drug. A smaller proportion of patients who were treated with midazolam nasal spray experienced the next seizure within 24 hours after the initial blinded dose (37.3% vs 46.3%). There was a statistically longer time to next seizure with midazolam nasal spray than with placebo, the company said.

The most common adverse reactions (≥5% in any midazolam nasal spray treatment group) were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.

Midazolam nasal spray is contraindicated in patients with acute narrow-angle glaucoma. Concomitant use of benzodiazepines, including midazolam nasal spray, and opioids may result in profound sedation, respiratory depression, coma, and death.

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