UCB Announces availability of NAYZILAM® (midazolam) Nasal Spray CIV, the first and only nasal rescue treatment for seizure clusters in the U.S.

ATLANTA, Nov. 25, 2019 /PRNewswire/ -- UCB announced today that 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.¹ 

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

"Delivering another of the six potential new product launches, a UCB mission over the next five years, NAZYILAM 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. NAZYILAM 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.^2-4 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.^5-8 Despite the impact of seizure clusters, many diagnosed patients may go untreated because currently available treatment options are not preferred.^9-12 Currently, only one in five people living with seizure clusters report using a rescue treatment.⁵ Many patients seek care in the emergency department.⁵

"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.^1,13 The most common adverse reactions (≥5% in any NAYZILAM treatment group) were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.¹  Midazolam is associated with a high incidence of partial or complete impairment of recall for the next several hours.¹

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.

It is anticipated that NAYZILAM prescriptions will cost commercial patients $40 per box.¹³ Each box contains two doses.¹ With the NAYZILAM Savings Card, eligible patients could pay $20 per box.¹³

For additional medical information about NAYZILAM, patient assistance, or any other information please visit NAYZILAM.com or call ucbCARES® at 1-844-599-2273. Full affordability information can be found at UCBUSA.news/Affordability.

UCB acquired NAYZILAM from Proximagen LLC in June 2018.

About NAYZILAM¹
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.

The effectiveness of NAYZILAM was established in a randomized, double-blind, placebo-controlled trial (Study 1; NCT01390220).

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.¹³ 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.^13,14 Midazolam is associated with a high incidence of partial or complete impairment of recall for the next several hours.

*Eligibility Criteria and Terms: The savings card is not valid for use by patients who are covered by any federal or state-funded healthcare program (including, but not limited to, Medicare [Part D and Medigap] and those who are Medicare-eligible and enrolled in an employer-sponsored health plan for retirees, Medicaid, any state pharmaceutical assistance program, TRICARE, VA, or DoD), or for cash-paying patients. A valid NAYZILAM prescription consistent with the approved FDA labeling is required. Other Eligibility Criteria and Terms apply. Full Eligibility Criteria and Terms are available at www.Nayzilam.com/Savings available upon request by calling ucbCARES® at 1-844-599-2273.

About Epilepsy^15-18
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.

About Seizure Clusters
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.^2-4 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.^5,19 These clusters are also distinguishable from a person's typical seizure pattern.⁵ 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.²⁰ Seizure clusters are a form of seizure emergency that can evolve into status epilepticus.⁵

About UCB in Epilepsy
UCB has a rich heritage in epilepsy with over 20 years of experience in the research and development of anti-epileptic drugs. As a company with a long-term commitment to epilepsy research, our goal is to address unmet medical needs. Our scientists are proud to contribute to advances in the understanding of epilepsy and its treatment. We partner and create super-networks with world-leading scientists and clinicians in academic institutions, pharmaceutical companies, and other organizations who share our goals. At UCB, we are inspired by patients, and driven by science in our commitment to support patients with epilepsy.

Important Safety Information for NAYZILAM¹
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.UCB-USA.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.

NAYZILAM® and ucbCARES® are registered trademarks of the UCB Group of Companies.
©2019 UCB, Inc., Smyrna, GA 30080. All rights reserved.

For further information, UCB:
U.S. Communications
Erica Puntel       
Communications, U.S.
T. 404.938.5359

Brand Communications
Jim Baxter 
Neurology Communications, UCB
T+32.2.473.78.85.01 jim.baxter@ucb.com

Investor Relations
Antje Witte         
Investor Relations, UCB
T +32.2.559.94.14 antje.witte@ucb.com

Isabelle Ghellynck,
Investor Relations, UCB
T+32.2.559.9588, isabelle.ghellynck@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 in immunology or neurology. With around 7 500 people, operating in 40 countries, the company generated revenue of € 4.6 billion in 2018. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCBUSA

Forward looking statements 
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, political, regulatory or clinical results and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions which could cause actual results to differ materially from those that may be 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, 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, product liability claims, challenges to patent protection for products or product candidates, 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. 

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. UCB is providing this information as of the date of this document and expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report a change in its expectations.

There is no guarantee that new product candidates in the pipeline will progress to product approval or that new indications for existing products will be developed and approved. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences between the partners. Also, UCB or others could discover safety, side effects or manufacturing problems with its products after they are marketed.

Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement.

References: 

1. NAYZILAM® (midazolam) nasal spray CIV. US Prescribing Information.
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. Kwan P, M Brodie. Early Identification of Refractory Epilepsy. NEJM. 2005. 342:314-319.
4. Chen B, Choi H, Hirsch L, et al. Prevalence and risk factors of seizure clusters in adult patients with epilepsy. Epilepsy Res. 2017;133:98-102.
5. 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.
6. Haut S. Seizure clusters: characteristics and treatment. Current Opinion Neurology. 28:143–150, 2015.
7. Buck D, et al. Patients' Experiences of Injury as a Result of Epilepsy. Epilepsia. 38(4):439-444, 1997.
8. Cereghino JJ, Mitchell WG, Murphy J, et al. Treating repetitive seizures with a rectal diazepam formulation: a randomized study. The North American Diastat Study Group. Neurology. 1998;51(5):1274-1282.
9. Holsti M, Dudley N, Schunk J, et al. Intranasal midazolam vs rectal diazepam for the home treatment of acute seizures in pediatric patients with epilepsy. Arch Pediatr Adolesc Med. 2010;164(8):747-753.
10. de Haan GJ, van der Geest P, Doelman G, Bertram E, Edelbroek P. A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations. Epilepsia. 2010;51(3):478-482
11. Nunley S, Glynn P, Rust S, Vidaurre J, Albert DVF, Patel AD. A hospital-based study on caregiver preferences on acute seizure rescue medications in pediatric patients with epilepsy: intranasal midazolam versus rectal diazepam. Epilepsy Behav. 2019;92:53-56.
12. Bhattacharyya M, Kalra V, Gulati S. Intranasal midazolam vs rectal diazepam in acute childhood seizures. Pediatr Neurol. 2006;34(5):355-359.
13. Data on File, UCB Inc.
14. Detyniecki K, Van Ess P, Sequeira D, Wheless J, Meng T, Pullman W. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters – a randomized, double-blind, placebo-controlled trial. Epilepsia. 2019;60; 1797-1808.
15. Centers for Disease Control and Prevention. Available at https://www.cdc.gov/epilepsy/basics/fast-facts.htm. Accessed 22 November 2019. 
16. The Epilepsy Foundation of America. About epilepsy basics. http://www.epilepsy.com/learn/about-epilepsy-basics. Accessed 22 November 2019. 
17. The Epilepsy Foundation of America. What is epilepsy? http://www.epilepsy.com/learn/epilepsy-101/what-epilepsy. Accessed 22 November 2019. 
18. The Epilepsy Foundation of America. Who gets epilepsy? http://www.epilepsy.com/learn/epilepsy-101/who-gets-epilepsy. Accessed 22 November 2019
19. The Epilepsy Foundation of America. Seizure Clusters. https://www.epilepsy.com/learn/challenges-epilepsy/seizure-emergencies/seizure-clusters. Accessed 22 November 2019.
20. Jafarpour S, Hirsch LJ, Gaínza-Leina M, et al. Seizure cluster: Definition, prevalence, consequences, and management. Seizure. 68:9-15.2019.

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