Midazolam Nasal Spray Treatment for Seizure Clusters to be Available in December

Midazolam nasal spray CIV (Nayzilam, UCB), an antiepileptic drug for treating intermittent stereotypic episodes of frequency seizure activity, will be available in retail pharmacies on December 2, 2019, according to a press release.¹

The drug, which was approved by the FDA in May 2019, is indicated for seizures that are distinct from a patient’s usual seizure pattern, in individuals age 12 years and older with epilepsy. Midazolam nasal spray CIV is the first and only rescue nasal treatment approved for this indication in the United States, according to UCB.²

UCB anticipates that midazolam will cost commercial patients $40 per box, with each box containing 2 doses. However, with co-pay assistance, eligible patients could pay $20 per box, according to UCB.¹

Midazolam nasal spray CIV is a ready-to-use solution that can be used when and where a seizure cluster occurs and allows for administration by a non-health care professional.²

More than 150,000 of US patients living with uncontrolled epilepsy experience seizure clusters, which are acute episodes of consecutives seizures that occur within a short period of time when a patient recovers during the interictal period. These clusters are also distinguishable from a person’s typical seizure pattern.²

“Seizure clusters are a medical emergency that can have very serious consequences for those living with them,” Laura Lubber, PhD, chief scientific officer of Citizens United for Research in Epilepsy (CURE), said in a statement.¹ “An effective seizure cluster rescue treatment, like Nayzilam, that is convenient and easily administered, along with a seizure cluster action plan, can change the lives of people living with seizure clusters and their families.”

The approval of midazolam was based on data from a placebo-controlled trial, with a primary efficacy endpoint of treatment success defined by 2 components: 1) seizure termination within 10 minutes and 2) no seizure recurrence within 6 hours.²

Split into 2 portions, the study included a test dose phase and a comparative phase. In the test doses phase, tolerability was assessed in 292 patients who, in the absence of a seizure, received two 5 mg doses of midazolam (10 mg total dosage) separated by 10 minutes. In the comparative phase, 201 patients treated a single seizure cluster episode in an outpatient setting with either a blinded dose of midazolam 5 mg or placebo. If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of midazolam 5 mg to be used between 10 minutes and 6 hours after administration of the initial blinded dose of the study drug.²

Overall, the results showed that a statistically significantly higher percentage of patients treated with midazolam met the primary efficacy endpoint (53.7% versus 34.3%; p=0.011).²

The study also evaluated the occurrence and time to next seizure after the initial blinded dose of the study drug. A smaller proportion of patients treated with midazolam experienced the next seizure within 24 hours after the initial blinded dose of study drug (37.3% versus 46.3%). Patients treated with midazolam experienced a statistically longer time-to-next-seizure than the placebo group, according to the study.²

For all seizure clusters treated with midazolam, the median time to return to full baseline functionality after study drug administration was approximately 90 minutes.²

The most common adverse reactions were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea. Midazolam is also associated with a high incidence of partial or complete impairment of recall for the next several hours.²

As with all benzodiazepines, including midazolam, concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death, according to UCB.¹

REFERENCES

• UCB Announces availability of Nayzilam (midazolam) Nasal Spray CIV, the first and only nasal rescue treatment for seizure clusters in the US [news release]. PR Newswire. https://www.prnewswire.com/news-releases/ucb-announces-availability-of-nayzilam-midazolam-nasal-spray-civ-the-first-and-only-nasal-rescue-treatment-for-seizure-clusters-in-the-us-300964269.html. Accessed November 25, 2019.
• UCB Announces Nayzilam (midazolam) nasal spray now approved by FDA to treat intermittent, stereotypic episodes of frequent seizure activity in people living with epilepsy in the US [news release]. UCB’s website. https://www.ucb.com/stories-media/Press-Releases/article/UCB-announces-NAYZILAM-midazolam-nasal-spray-now-approved-by-FDA-to-treat-intermittent-stereotypic-episodes-of-frequent-seizure-activity-in-people-living-with-epilepsy-in-the-U-S. Accessed November 25, 2019.