Midazolam nasal spray CIV, marketed under the brand name Nayzilam, is expected to become available in retail pharmacies early next month after its approval for the treatment of intermittent, stereotypic episodes of frequent seizure activity in epilepsy.
Mike Davis, MBA, head, US Neurology, UCB
Mike Davis, MBA
UCB has announced that its midazolam nasal spray CIV, marketed under the brand name Nayzilam, is expected to become available in retail pharmacies on December 2, 2019. The therapy is approved for the treatment of intermittent, stereotypic episodes of frequent seizure activity, including seizure clusters and acute repetitive seizures, distinct from that of a patient’s usual seizure pattern.1
"Delivering another of the six potential new product launches, a UCB mission over the next five years, Nayzilam builds on UCB's commitment to addressing the unmet needs of people living with epilepsy," Mike Davis, MBA, head, US Neurology, UCB, said in a statement. "For the first time, people 12 years and older now have a nasally administered rescue therapy shown to help manage seizure clusters. Nayzilam can be administered anywhere seizure clusters strike, allowing families to take back valuable moments that would otherwise be lost."
The benzodiazepine is the first and only rescue nasal option for seizure clusters, and was approved in May 2019. According to estimates, up to 150,000 patients in the US experience seizure clusters in addition to their uncontrolled epilepsy, and only 20% of those with seizure clusters report using a rescue treatment, resorting instead to emergency care in some cases.2,3
"Seizure clusters are a medical emergency that can have very serious consequences for those living with them," said Laura Lubbers, PhD, chief scientific officer, Citizens United for Research in Epilepsy (CURE), in a statement. "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."
Midazolam may be administered in the outpatient setting by a non-healthcare professional in patients actively seizing and where a seizure cluster occurs. It is supplied as 2 single-use nasal spray units, each containing a 5 mg dose of midazolam in 0.1 mL solution. The prescribing information warns that concomitant use of benzodiazepines, including midazolam, and opioids may result in intense sedation, respiratory depression, coma, and death, and for patients at increased risk of respiratory depression, administration of midazolam under healthcare supervision should be considered prior to treatment.4
The effectiveness of midazolam was established in a phase 3 randomized, double-blind, placebo-controlled trial (NCT01390220) that was conducted in 2 phases: an open-label test dose phase followed by a comparative phase. Phase 1 of the trial included patients with epilepsy on a stable regimen of antiepileptic drugs identified as having intermittent, stereotypic episodes of frequent seizure activity distinct from the patient's usual seizure pattern.5
In the test dose phase, tolerability was assessed in 292 patients who, in the absence of a seizure, received 2, 5 mg doses of midazolam 10 minutes apart. Study participants that failed to meet pre-identified blood pressure, heart rate, sedation, electrocardiogram, and peripheral oxygen saturation criteria were excluded from participating in the comparative phase.
In the comparative phase, patients treated a single seizure cluster episode in an outpatient setting with either a blinded dose of midazolam 5 mg (n = 134 patients) or placebo (n = 67). Both groups had the option to receive a subsequent unblinded dose of midazolam 5 mg, which was used between 10 minutes and 6 hours after administration of the initial dose, in the case of persistent seizures.
The primary efficacy endpoint was treatment success, defined as achieving both of the following: termination of the seizure(s) within 10 minutes after study drug administration, and no recurrence of seizures spanning the window of 10 minutes to 6 hours after administration. Investigators reported that a statistically significant higher percentage of patients treated with midazolam met the primary efficacy endpoint; termination of seizure(s) within 10 minutes after the initial dose of study drug (80.6% versus 70.1%) and the absence of seizure(s) recurrence between 10 minutes and 6 hours after the initial dose of midazolam (58.2% versus 37.3%).
Additionally, Study 1 also evaluated the occurrence and time to the next seizure after the initial blinded study dose and saw that a smaller proportion of midazolam-treated patients experienced the next seizure 24 hours after the initial dose of midazolam (37.3% versus 46.3%).
The most common adverse reactions ≥5% in any midazolam treatment group in the trial were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
1. UCB Announces availability of NAYZILAM® (midazolam) Nasal Spray CIV, the first and only nasal rescue treatment for seizure clusters in the U.S. [press release]. Atlanta, GA: UCB; Published November 25, 2019. 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 26, 2019.
2. Zack M, R Kobau. National and State Estimates of the Numbers of Adults and Children with Active Epilepsy. CDC MMWR. 2017. 66:821-825.
3. Penovich PE, Buelow J, Steinberg, et al. Burden of seizure clusters on patients with epilepsy and caregivers survey of patient, caregiver, and clinician perspectives. The Neurologist. 2017;22:207—214.
5. 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. [news release]. Brussels, Belgium, Atlanta, Ga.: UCB; May 20, 2019. 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 26, 2019.