UCB announced NAYZILAM® (midazolam) nasal spray CIV will be available in retail pharmacies on December 2, 2019, for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 12 years of age and older.
NAYZILAM is the first and only rescue nasal treatment approved to treat seizure clusters in the U.S. NAYZILAM is a ready-to-use solution that can be used when and where a seizure cluster occurs and can be administered by a non-healthcare professional to a patient during or after a seizure within a cluster. As with all benzodiazepines, including NAYZILAM, concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
"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," said Mike Davis, Head of Neurology in the U.S., UCB. "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."
It is estimated that more than 150,000 people in the U.S. with uncontrolled epilepsy also experience seizure clusters. Rescue treatment of seizure clusters is critical because when left untreated, seizure clusters can increase the risk of physical injury, neurological damage, and status epilepticus. Despite the impact of seizure clusters, many diagnosed patients may go untreated because currently available treatment options are not preferred. Currently, only one in five people living with seizure clusters report using a rescue treatment. Many patients seek care in the emergency department.
"Seizure clusters are a medical emergency that can have very serious consequences for those living with them," said Dr. Laura Lubbers, Chief Scientific Officer, Citizens United for Research in Epilepsy (CURE). "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 NAYZILAM was based on 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.1 NAYZILAM helped the majority of patients stop a seizure cluster fast and helped patients return to baseline function in approximately 90 minutes. The most common adverse reactions (≥5% in any NAYZILAM treatment group) were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea. Midazolam is associated with a high incidence of partial or complete impairment of recall for the next several hours.
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UCB is committed to finding solutions for patients with unmet needs, including people living with seizure clusters. NAYZILAM builds on UCB's long-standing leadership in epilepsy and commitment to enabling patients to live their best lives.
UCB acquired NAYZILAM from Proximagen in June 2018.
NAYZILAM® (midazolam) nasal spray CIV is a benzodiazepine indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern in patients with epilepsy 12 years of age and older.
Study 1 enrolled patients with epilepsy on a stable regimen of antiepileptic drugs who were identified by their physicians as having intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient's usual seizure pattern.
Study 1 was conducted in two phases: an open-label Test Dose Phase followed by a randomized, double-blind, placebo-controlled, 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 NAYZILAM (10 mg total dosage) separated by 10 minutes. Patients were excluded from participation in the Comparative Phase if they failed to meet pre-defined blood pressure, heart rate, sedation, electrocardiogram, and peripheral oxygen saturation criteria.
In the Comparative Phase, 201 patients treated a single seizure cluster episode in an outpatient setting with either a blinded dose of NAYZILAM 5 mg (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of NAYZILAM 5 mg to be used between 10 minutes and 6 hours after administration of the initial blinded dose of study drug.
The primary efficacy endpoint for Study 1 was treatment success, defined as the termination of seizures within 10 minutes after the initial blinded dose of study drug and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug. A statistically significantly higher percentage of NAYZILAM-treated patients met the primary efficacy endpoint (53.7 versus 34.3%; p=0.011).
Numerical differences in favor of NAYZILAM were observed on each of the components of the treatment success responder definition; termination of seizure(s) within 10 minutes after initial dose of study drug (80.6 versus 70.1%) and the absence of seizure recurrence between 10 minutes and 6 hours after the initial dose of study drug (58.2 versus 37.3%). The most common adverse reactions (≥5% in any NAYZILAM treatment group) were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
Study 1 also evaluated the occurrence and time to next seizure after the initial blinded dose of study drug. A smaller proportion of NAYZILAM-treated patients experienced the next seizure within 24 hours after the initial blinded dose of study drug (37.3% versus 46.3%). NAYZILAM-treated patients experienced a statistically longer time-to-next-seizure than the placebo group.
For all seizure clusters treated with NAYZILAM, the median time to return to full baseline functionality after trial drug administration was approximately 90 minutes. Patients' return to baseline functionality was evaluated by recording the time when the subject was able to return to what he/she was doing prior to having a seizure cluster. Midazolam is associated with a high incidence of partial or complete impairment of recall for the next several hours.
Epilepsy is a chronic neurological disorder of the brain. It is the fourth most common neurological condition worldwide and affects approximately 65 million people. In the U.S. more than 3.4 million people have epilepsy. Anyone can develop epilepsy; it occurs across all ages, races and genders, and is defined as one or more unprovoked seizures with a risk of further seizures. Around one third of patients with epilepsy currently live with uncontrolled seizures.
Among the one third of patients living with uncontrolled epilepsy, it is estimated that more than 150,000 of these patients in the U.S. experience seizure clusters. Seizure clusters are broadly defined as acute episodes of consecutive 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. Other names for seizure clusters include acute-repetitive seizures (ARS), serial seizures, crescendo seizures, and seizure flurries, which highlight the repetitive nature of the seizures. Seizure clusters are a form of seizure emergency that can evolve into status epilepticus.