• Median time to return to full baseline function occurred within 90 minutes following outpatient treatment with NAYZILAM^® (midazolam) nasal spray, with a similar effect in those receiving either one or two doses
• Median time to return to full baseline function was stable over the course of repeated, intermittent use
• Returning to full baseline function after using a rescue medication for seizure clusters (SCs) is critically important to patients and caregivers as it affects when patients can return to work, school daily activities, and hobbies
• NAYZILAM, approved by the US Food and Drug Administration (FDA) in 2019, is a nasal treatment for seizure clusters in people 12 years of age or older 

ATLANTA, GA, October 31, 2023 7 a.m. (EST) – UCB, a global biopharmaceutical company, today announced that Epilepsy & Behavior published a post hoc analysis from the Phase 3 open-label extension study of NAYZILAM. This analysis showed the estimated median time to RTFBF, regardless of treatment with one or two doses, was 90 minutes. While most patients required a single 5-mg spray to treat the cluster, patients and caregivers had the option to administer a second 5-mg dose after only 10 minutes if needed.  This publication characterized the impact of one or two doses on the time to RTFBF.¹

The Phase 3 open-label extension (OLE) study evaluated the safety of repeated, intermittent use of NAYZILAM in individuals living with epilepsy experiencing acute repetitive seizures, also known as seizure clusters. Patients were followed for a median of 17 months and 7 treated seizure clusters per patient. The use of a second dose did not increase over treated cluster episodes.¹

The time taken for patients to RTFBF after using a rescue medication for SCs is critically important to patients and caregivers as it affects when patients can return to work, school, daily activities, and hobbies. “For people living with epilepsy who unfortunately experience seizure clusters, the ability to get back to their everyday lives after these episodes is critical. The convenience of a nasal treatment which allows a quick return to what they were doing before the cluster can have a profound impact for both the person with epilepsy and the caregiver supporting them,” said Brad Chapman, Head of US Epilepsy & Rare Syndromes at UCB. “The publication of these results underscores our commitment to science driven patient outcomes and improved health for people experiencing seizure clusters and those who care for them.”

The post hoc analysis represents 1,996 treated seizure cluster episodes in 161 patients. NAYZILAM 5-mg was administered by a caregiver when a patient experienced a seizure cluster. Another 5-mg dose could be given if the seizure did not terminate within 10 minutes or if there was seizure recurrence within 6 hours. Results showed the median time to RTFBF was similar in patients treated with either one or two doses of NAYZILAM (approximately 30% within 30 minutes, and nearly 50% within 1 hour), suggesting that the dose of NAYZILAM does not influence the RTFBF. In the study, 97.2% of patients treated with one dose and 94.2% of patients treated with two doses experienced RTFBF within 24 hours of administration. Additionally, 45.9% of patients treated with one dose and 44.7% of patients treated with two doses of NAYZILAM experienced RTFBF within 1 hour of administration.¹

“This study suggests that people who used NAYZILAM had the ability to get back to their daily lives within several hours of their seizure clusters, and that their ability to return to baseline function was not influenced by the number of doses used,” said Dr. Detyniecki, study co-author. “These findings – together with previous efficacy and safety data – further support the repeated intermittent use of NAYZILAM as a rescue therapy to help people with epilepsy experiencing seizure clusters treat the cluster and return to their full baseline functionality post-seizure as quickly as possible.”

Seizure clusters are episodes of frequent seizure activity that are distinct from a person’s usual seizure pattern.² They can be triggered by missed doses or changes in medication, menstrual cycles, and stress, among other factors.³ If left untreated, seizure clusters can result in emergency room visits or potentially more serious consequences, including status epilepticus and death.^4,5 Three out of four people living with epilepsy live in fear of having their next seizure cluster.⁶ The time it takes to recover physically and cognitively following a seizure cluster can negatively impact a person’s quality of life, including their ability to go to school or work, or participate in social activities.⁶

About Epilepsy
Epilepsy is a common neurological condition worldwide and affects approximately 50 million people.⁷ Epilepsy and seizures can develop in any person at any age,⁸ and is usually diagnosed after a person has had at least two seizures (or after one seizure with a high risk for more) that were not caused by some known medical condition.⁹

About UCB in Epilepsy
For three decades, we’ve been committed to people living with epilepsy and their families, surrounding the patient and caregiver through every step of their care journey. At our core, we have a responsibility to elevate the healthcare ecosystem. Because of this, we have established our legitimacy on the front lines of epilepsy research, development, and treatment innovation. But our past breakthroughs are only a prologue to our future. We will continue to reimagine how we care for patients, leveraging today's expertise for a better tomorrow. With so much experience behind us and so much potential ahead, we are more invested than ever in profoundly improving the lives of those living with or caring for those with epilepsy or a rare epilepsy syndrome – through our relentless pursuit of a seizure-free life.

Important Safety Information for NAYZILAM
NAYZILAM^® is 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.
 
CONTRAINDICATIONS
NAYZILAM is contraindicated in patients with acute narrow-angle glaucoma.
 
RISKS FROM CONCOMITANT USE WITH OPIOIDS
Concomitant use of benzodiazepines, including NAYZILAM, and opioids may result in profound sedation, respiratory depression, coma, and death. 

• Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.

RISKS OF CARDIORESPIRATORY ADVERSE REACTIONS
Serious cardiorespiratory adverse reactions have occurred after administration of midazolam. Warn patients and caregivers about the risks of respiratory depression, cardiac and respiratory arrest.
 
Respiratory depression was observed with the administration of NAYZILAM during clinical trials. Cardiac or respiratory arrest caused by NAYZILAM was not reported during clinical trials.
 
CENTRAL NERVOUS SYSTEM DEPRESSION FROM CONCOMITANT USE WITH OTHER CENTRAL NERVOUS SYSTEM DEPRESSANTS, OR MODERATE OR STRONG CYP3A4 INHIBITORS
Drug products containing midazolam, including NAYZILAM, have a central nervous system (CNS) depressant effect. 
 
Risks from Concomitant Use with Other CNS Depressants
NAYZILAM may cause an increased CNS-depressant effect when used with alcohol or other CNS depressants (e.g., opioids). Warn patients and caregivers that the use of NAYZILAM in combination with alcohol or other CNS depressant drugs may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
 
Risks from Concomitant Use with Moderate or Strong CYP3A4 Inhibitors
Concomitant use of NAYZILAM with moderate or strong CYP3A4 enzyme inhibitors may result in prolonged sedation because of a decrease in plasma clearance of midazolam. Caution patients against engaging in hazardous occupations requiring mental alertness, such as operating machinery, driving a motor vehicle or riding a bicycle until they have completely returned to their level of baseline functioning.
 
SUICIDAL BEHAVIOR AND IDEATION
Antiepileptic drugs (AEDs), including NAYZILAM, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients treated with NAYZILAM for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients and caregivers to be alert for these behavioral changes and to immediately report them to the healthcare provider.
 
IMPAIRED COGNITIVE FUNCTION
Midazolam, including NAYZILAM, is associated with a high incidence of partial or complete impairment of recall for several hours following an administered dose. Counsel patients on when they can engage in activities requiring complete mental alertness, operate hazardous machinery, or drive a motor vehicle after taking NAYZILAM.
 
GLAUCOMA
Benzodiazepines, including NAYZILAM, can increase intraocular pressure in patients with glaucoma. NAYZILAM may be used in patients with open-angle glaucoma only if they are receiving appropriate therapy. NAYZILAM is contraindicated in patients with narrow-angle glaucoma.
 
ADVERSE REACTIONS
In the randomized, double-blind, placebo-controlled trial, the most common adverse reactions (≥5% in any NAYZILAM treatment group) were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.
 
NAYZILAM is a Schedule IV controlled substance.
 
Please refer to the full Prescribing Information at www.Nayzilam.com.
 
For additional medical information about NAYZILAM, patient assistance, or any other information please visit our website or call UCBCares^® at 1-844-599-2273.

For further information, contact UCB: 

Investor Relations
Antje Witte
T: +32.2.559.94.14 
email antje.witte@ucb.com 

US Communications
Becky Malone
T +1.919.605.9600
Email becky.malone@ucb.com 

About UCB 
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With approximately 8,700 people in approximately 40 countries, the company generated revenue of €5.5 billion in 2022. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCBUSA.

Forward looking statements 
This press release may contain forward-looking statements including, without limitation, statements containing the words “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will”, “continue” and similar expressions. These forward-looking statements are based on current plans, estimates and beliefs of management. All statements, other than statements of historical facts, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, arbitration, political, regulatory or clinical results or practices and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties and assumptions which might cause the actual results, financial condition, performance or achievements of UCB, or industry results, to differ materially from those that may be expressed or implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms or within expected timing, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, product liability claims, challenges to patent protection for products or product candidates, competition from other products including biosimilars, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws, and hiring and retention of its employees. There is no guarantee that new product candidates will be discovered or identified in the pipeline, will progress to product approval or that new indications for existing products will be developed and approved. Movement from concept to commercial product is uncertain; preclinical results do not guarantee safety and efficacy of product candidates in humans. So far, the complexity of the human body cannot be reproduced in computer models, cell culture systems or animal models. The length of the timing to complete clinical trials and to get regulatory approval for product marketing has varied in the past and UCB expects similar unpredictability going forward. Products or potential products, which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences disputes between the partners or may prove to be not as safe, effective or commercially successful as UCB may have believed at the start of such partnership. UCB’s efforts to acquire other products or companies and to integrate the operations of such acquired companies may not be as successful as UCB may have believed at the moment of acquisition. Also, UCB or others could discover safety, side effects or manufacturing problems with its products and/or devices after they are marketed. The discovery of significant problems with a product similar to one of UCB’s products that implicate an entire class of products may have a material adverse effect on sales of the entire class of affected products. Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment, including pricing pressure, political and public scrutiny, customer and prescriber patterns or practices, and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement activities and outcomes. Finally, a breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of UCB’s data and systems. 

Given these uncertainties, you should not place undue reliance on any of such forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labelling in any market, or at any particular time, nor can there be any guarantee that such products will be or will continue to be commercially successful in the future.

UCB is providing this information, including forward-looking statements, only as of the date of this press release. UCB expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report or reflect any change in its forward-looking statements with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless such statement is required pursuant to applicable laws and regulations. 

Additionally, information contained in this document shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any offer, solicitation or sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such jurisdiction. 

References

1. Detyniecki, K., Brunnert, M., Campos, R., Dimova, S., & Wheless, J. W. (2023). Return to full baseline functionality after repeated intermittent use of midazolam nasal spray in patients with seizure clusters: Post hoc analysis of an open-label extension trial. Epilepsy & Behavior, 148, 109483. 
2. Penovich PE, Buelow J, Steinberg K, 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.
3. Jafarpour S, Hirsch LJ, Gaínza-Lein M, Kellinghaus C, Detyniecki K. Seizure cluster: definition, prevalence, consequences, and management. Seizure. 2019;68:9-15. 
4. Haut SR, Shinnar S, Moshé SL, O'Dell C, Legatt AD. The association between seizure clustering and convulsive status epilepticus in patients with intractable complex partial seizures. Epilepsia. 1999;40(12):1832-1834. 
5. Sillanpää M, Schmidt D. Seizure clustering during drug treatment affects seizure outcome and mortality of childhood-onset epilepsy. Brain. 2008;131(Pt 4):938-944.
6. Penovich PE, Buelow J, Steinberg K, Sirven J, Wheless J. Burden of seizure clusters on patients with epilepsy and caregivers: survey of patient, caregiver, and clinician perspectives. Neurologist. 2017;22:207-14.
7. Meyer AC, Dua T, Ma J, et al. Global disparities in the epilepsy treatment gap: a systemic review. Bull World Health Organ. 2010;88: 260-266.
8. Epilepsy Foundation. Who Can Get Epilepsy? Available at: https://www.epilepsy.com/learn/about-epilepsy-basics/who-gets-epilepsy. (Last accessed: November 2022).
9. Epilepsy Foundation: What is Epilepsy? Available at: https://www.epilepsy.com/learn/about-epilepsy-basics. (Last accessed: November 2022).

US-NZ-2300021
Date of preparation: October 2023
NAYZILAM® is a registered trademark of the UCB Group of Companies.
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