• Study met primary and secondary endpoints of significantly lowering the risk of developing a second primary generalized tonic-clonic seizure (PGTCS) during a 24-week treatment and a significantly higher rate of freedom from PGTCS during the treatment period compared with placebo 
• Lacosamide was generally tolerated by patients enrolled in the study
• Regulatory reviews, based, in part, on these data, are currently underway in the U.S., EU, Japan, and Australia
• VIMPAT®  is currently not approved for PGTCS in any country in the world

Atlanta, Ga. (31 August  2020, 7am ET) - UCB, a global biopharmaceutical company, today announced the publication of the Phase 3 study results of VIMPAT^®  (lacosamide) CV as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures (PGTCS), in the Journal of Neurology, Neurosurgery & Psychiatry.¹

The Phase 3 study enrolled 242 patients (≥4 years of age) with idiopathic generalized epilepsy (IGE) who were randomized 1:1 to receive lacosamide or placebo (twice daily) in addition to their current epilepsy treatment. The primary endpoint was time to second primary generalized tonic-clonic seizure (PGTCS) during the 24-week (166-day) treatment period. 

Treatment with lacosamide resulted in a significantly lower risk of developing a second PGTCS during the 24-week treatment (HR 0.540; p<0.001) and a significantly higher rate of freedom from PGTCS during the treatment period compared with placebo (31.3% vs 17.2%, p=0.011). Lacosamide was generally tolerated in patients with IGE and PGTCS. The most common treatment-emergent adverse events (≥10%) with lacosamide were dizziness (23.1%), somnolence (16.5%) and headache (14.0%). The incidences of dizziness and headache were numerically higher with lacosamide than placebo.

VIMPAT^® is currently not approved for PGTCS in any country in the world. Regulatory reviews for use of VIMPAT as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy four years of age and older compared to placebo are currently underway in the U.S., EU, Japan, and Australia.

“This Phase 3 trial demonstrated that by adding lacosamide to existing anti-seizure medications, IGE patients with uncontrolled primary generalized tonic-clonic seizures experienced a higher rate of seizure freedom, suggesting lacosamide could be a valuable adjunctive therapy in this patient population,” said David Vossler, MD, FAAN FACNS FAES, Department of Neurology, University of Washington, USA.

IGEs account for 20%–40% of all epilepsies²  and are characterized by different generalized seizure types (absence, myoclonic and PGTCS).³ Patients living with generalized tonic-clonic seizures have an increased risk of injury⁴ and those who experienced three or more in one year had a fifteen-fold increased risk of sudden unexpected death in epilepsy.⁵

“UCB remains committed to strengthening our leadership in epilepsy and to investigating new approaches and innovative solutions to deliver improved outcomes and experiences to the global epilepsy community. This applies equally to our current expansive in-market epilepsy portfolio as well as to our exciting pipeline,” explained Charl van Zyl, Executive Vice President & Head of Neurology Solutions, UCB.

About the Study¹
The study (SP0982; NCT02408523) was a Phase 3, double-blind, randomized, placebo-controlled, multicenter study in patients with IGE and PGTCS taking 1–3 concomitant anti-epileptic drugs (AEDs). The primary outcome was time to second PGTCS during 24-week treatment. 242 eligible patients were randomized 1:1 to receive lacosamide or placebo (twice daily). Patients were eligible if they were ≥4 years of age with a confirmed diagnosis of IGE experiencing classifiable PGTCS. The treatment period continued until one of the following occurred: completion of ≥6 weeks of the treatment period and occurrence of two or more PGTCS, completion of the 24-week treatment period without occurrence of two PGTCS, or the 125th event occurred in the trial.

About VIMPAT® (lacosamide) CV in the U.S.⁶
VIMPAT® was approved in the U.S. in 2008 as an add-on therapy for adult patients. VIMPAT was approved as monotherapy for adults in August 2014, and as monotherapy or adjunctive therapy in patients four years of age and older with partial-onset seizures in 2017. VIMPAT is available in three formulations: oral tablets, oral solution, and intravenous (IV) injection. 

VIMPAT U.S. INDICATION AND IMPORTANT SAFETY INFORMATION 

VIMPAT^® is indicated for the treatment of partial-onset seizures in patients 4 years of age and older.

As the safety of VIMPAT injection in pediatric patients has not been established, VIMPAT injection is indicated for the treatment of partial-onset seizures only in adult patients (17 years of age and older).

^{IMPORTANT SAFETY INFORMATION 
WARNINGS AND PRECAUTIONS}

• Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including VIMPAT, increase the risk of suicidal behavior and ideation. Monitor patients taking VIMPAT 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.
   
• Dizziness and Ataxia: VIMPAT may cause dizziness and ataxia. In adult clinical trials, the onset of dizziness and ataxia was most commonly observed during titration. Advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they are familiar with the effects of VIMPAT on their ability to perform such activities. Dizziness and ataxia were also observed in pediatric clinical trials.
   
• Cardiac Rhythm and Conduction Abnormalities 
  PR Interval Prolongation, Atrioventricular Block, and Ventricular Tachyarrhythmia 
  Dose-dependent prolongations in PR interval with VIMPAT have been observed in clinical studies in adult patients and in healthy volunteers. When VIMPAT is given with other drugs that prolong the PR interval, further PR prolongation is possible.
  
  In the postmarketing setting, there have been reports of cardiac arrhythmias in patients treated with VIMPAT, including bradycardia, AV block, and ventricular tachyarrhythmia, which have rarely resulted in asystole, cardiac arrest, and death. Most, although not all, cases have occurred in patients with underlying proarrhythmic conditions, or in those taking concomitant medications that affect cardiac conduction or prolong the PR interval. These events have occurred with both oral and intravenous routes of administration and at prescribed doses as well as in the setting of overdose.
  
  VIMPAT should be used with caution in patients with underlying proarrhythmic conditions such as known cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block, and sick sinus syndrome without pacemaker), severe cardiac disease (such as myocardial ischemia or heart failure, or structural heart disease), and cardiac sodium channelopathies (e.g., Brugada Syndrome).
  
  VIMPAT should also be used with caution in patients on concomitant medications that affect cardiac conduction, including sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers, and medications that prolong the PR interval. In such patients, obtaining an ECG before beginning VIMPAT, and after VIMPAT is titrated to steady-state maintenance dose, is recommended. In addition, these patients should be closely monitored if they are administered VIMPAT through the intravenous route. Patients should be made aware of and report cardiac signs or symptoms to their healthcare provider right away.

Atrial Fibrillation and Atrial Flutter
VIMPAT administration may predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy and/or cardiovascular disease.
 

• Syncope: VIMPAT may cause syncope in adult and pediatric patients.
   
• Withdrawal of Antiepileptic Drugs: Gradually withdraw VIMPAT (over a minimum of 1 week) to minimize the potential of increased seizure frequency.
   
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Also known as multi- organ hypersensitivity, has been reported with antiepileptic drugs, including VIMPAT. Some of these events have been fatal or life-threatening. If signs or symptoms are present, immediately evaluate the patient. Discontinue VIMPAT if an alternative etiology for the signs and symptoms cannot be established.
   
• Risks in Patients with Phenylketonuria: VIMPAT oral solution contains aspartame, a source of phenylalanine, which can be harmful in patients with phenylketonuria (PKU). A 200 mg dose of VIMPAT oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine.

Adverse Reactions

• Adjunctive therapy: In the adult placebo-controlled clinical trials, the most frequently seen adverse reaction with VIMPAT was dizziness (31% vs 8% placebo). Other common adverse reactions occurring in ≥10 percent of VIMPAT-treated patients, and greater than placebo, were headache, nausea, and diplopia.
   
• Monotherapy: In the adult clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo-controlled trials, with the exception of insomnia (occurred at a higher rate of ≥2%).
   
• Pediatric patients: Adverse reactions reported in clinical studies of pediatric patients 4 to less than 17 years of age were similar to those seen in adult patients.
   
• Injection: In adult adjunctive therapy clinical trials, adverse reactions with intravenous administration generally were similar to those that occurred with the oral formulation, although intravenous administration was associated with local adverse reactions such as injection site pain or discomfort (2.5%), irritation (1%), and erythema (0.5%). When administering a loading dose, the incidence of CNS adverse reactions, such as dizziness, somnolence, and paresthesia, may be higher with 15-minute administration than over a 30- to 60- minute period.

Dosing Considerations

VIMPAT injection is for intravenous and adult use only when oral administration is temporarily not feasible. The loading dose for adult patients should be administered with medical supervision considering the VIMPAT pharmacokinetics and increased incidence of CNS adverse reactions. The safety of VIMPAT injection and the use of a loading dose in pediatric patients have not been studied. Dosage adjustments are recommended for patients with mild or moderate hepatic impairment or severe renal impairment. Use in patients with severe hepatic impairment is not recommended. Perform dose titration with caution in all patients with renal and/or hepatic impairment.

VIMPAT is a Schedule V controlled substance.

Please refer to full Prescribing Information.

About Epilepsy
Epilepsy is the main symptom of a variety of chronic disorders of the brain. It is the fourth most common neurological condition worldwide and affects approximately 65 million people.⁷ Anyone can develop epilepsy; it occurs across all ages, races and genders, and is defined as one or more unprovoked epileptic seizures with a risk of further seizures.⁸

About UCB in Epilepsy
UCB has a rich heritage in epilepsy with over 30 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.

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 more than 7,600 people in approximately 40 countries, the company generated revenue of € 4.9 billion in 2019. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news

For further information, UCB: 

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

Erica Puntel
U.S. Neurology Communications, UCB
404-938-5359, Erica.puntel@ucb.com

Corporate Communications
Laurent Schots 
Media Relations, UCB  
T+32.2.559.92.64  Laurent.schots@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 

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VIMPAT^® is a registered trademark used under license from Harris FRC Corporation.
©2020 UCB, Inc., Smyrna, GA 30080. All rights reserved.

Forward looking statements UCB
This press release contains 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, 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 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’ 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 and 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. Vossler DG, et al. Efficacy and safety of adjunctive lacosamide in the treatment of primary generalised tonic-clonic seizures: a double-blind, randomized, placebo-controlled trial. J Neurol Neurosurg Psychiatry 2020;0:1–9. doi:10.1136/jnnp-2020-323524
2. Marini C., King M.A., Archer J.S., Newton M.R., Berkovic S.F. Idiopathic generalised epilepsy of adult onset: clinical syndromes and genetics. J Neurol Neurosurg Psychiatry 2003; 74(2):192–6
3. Benbadis SF. Practical management issues for idiopathic generalised epilepsies. Epilepsia. 2005;46(Suppl 9):125-132. 
4. Asadi-Pooya AA, Nikseresht A, Yaghoubi E, et al. Physical injuries in patients with epilepsy and their associated risk factors. Seizure 2012;21:165–8.
5. DeGiorgio CM, et al. Ranking the leading risk factors for sudden unexpected death in epilepsy. Front Neurol. 2017;8:473
6. VIMPAT® (lacosamide) CV. U.S. Prescribing Information
7. Epilepsy Foundation. Who gets epilepsy? https://www.epilepsy.com/learn/about-epilepsy-basics/what-epilepsy  https://www.epilepsy.com/learn/about-epilepsy-basics/who-gets-epilepsy. Date Accessed 24th August 2020
8. International League Against Epilepsy. Definition of Epilepsy 2014.  https://www.ilae.org/guidelines/definition-and-classification/definition-of-epilepsy-2014. Date Accessed 24th August 2020