UCB announces FDA approval for Keppra® in infants and children from one month of age with partial onset seizures

Brussels, BELGIUM – January 25th, 2012, 0700 CET – UCB announced today that the U.S. Food and Drug Administration (FDA) has approved Keppra® (levetiracetam) tablets and oral solution as adjunctive therapy in the treatment of partial onset seizures in adults and children one month of age and older with epilepsy. Keppra® was previously approved in the U.S. as adjunctive therapy for partial onset seizures in adults and children four years of age and older with epilepsy.

“As a leader in epilepsy UCB has a responsibility to develop effective medicines that address unmet medical needs,” said Professor Dr. Iris Loew-Friedrich, Chief Medical Officer and Executive Vice President UCB. “Our continuing development program with Keppra® in young children demonstrates our long-term commitment to epilepsy.”

The approval was based on data from a phase III, double-blind, randomized, multi-centre, placebo-controlled study evaluating the efficacy and tolerability of Keppra® oral solution (20-50 mg/kg/day) in 116 pediatric patients with refractory partial onset seizures, aged from one month to under four years. Keppra® was shown to significantly reduce the frequency of partial onset seizures with 43.1% of Keppra®-treated patients experiencing at least a 50% reduction in seizure frequency during the evaluation period (five days) compared with 19.6% of placebo-treated patients (p=0.013). Keppra® was generally well-tolerated in this pediatric population. The most commonly reported adverse events that occurred more frequently in the treatment group were somnolence (13.3% vs. 1.8% for placebo) and irritability (11.7% vs. 0% for placebo).¹

In 2009, the European Commission granted marketing authorisation for Keppra® in the European Union as adjunctive treatment of partial onset seizures in infants and young children aged one month to under four years. Keppra® has provided the foundation for UCB's growing epilepsy franchise which has been extended to include Vimpat® (lacosamide) which is marketed in the European Union as adjunctive therapy for the treatment of partial onset seizures with or without secondary generalization in patients with epilepsy, aged 16 years and older and in the U.S. as adjunctive therapy in the treatment of partial onset seizures in patients with epilepsy, aged 17 years and older. In the U.S. Vimpat® is a Schedule V controlled substance.

About Keppra®
In the U.S. Keppra® tablets and oral solution are indicated as adjunctive therapy in the treatment of partial onset seizures in adults and children one month of age and older with epilepsy, myoclonic seizures in adults and adolescents 12 years of age and older with juvenile myoclonic epilepsy, and primary generalized tonic-clonic seizures in adults and children 6 years of age and older with idiopathic generalized epilepsy. Keppra® injection is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults (≥16 years of age) with idiopathic generalized epilepsy, myoclonic seizures in adults with juvenile myoclonic epilepsy and partial onset seizures in adults with epilepsy. Keppra® injection is an alternative for patients when oral administration is temporarily not feasible.

In the European Union Keppra® is indicated as monotherapy in the treatment of partial onset seizures with or without secondary generalization in patients from 16 years of age with newly diagnosed epilepsy. Keppra® is indicated as adjunctive therapy in the treatment of partial onset seizures with or without secondary generalization in adults, infants and children from 1 month of age with epilepsy. Keppra® is indicated as adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy. Keppra® is indicated as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and adolescents from 12 years of age with idiopathic generalized epilepsy. Keppra® concentrate is an alternative for patients when oral administration is temporarily not feasible.

Keppra® in the U.S. - Important Safety Information
Antiepileptic drugs (AEDs) increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Keppra® is also associated with the occurrence of central nervous system adverse events including somnolence and fatigue and behavioral abnormalities (e.g., psychotic symptoms, suicidal ideation and other abnormalities). Keppra® should be gradually withdrawn to minimize the potential of increased seizure frequency. In adults experiencing partial onset seizures, the most common adverse events associated with Keppra® in combination with other AEDs were somnolence, asthenia, infection and dizziness. In pediatric patients, the most common adverse events associated with Keppra® in combination with other AEDs were fatigue, aggression, nasal congestion, decreased appetite, and irritability. The adverse reactions for patients with JME and PGTC seizures are expected to be essentially the same as for patients with partial seizures. The adverse reactions for Keppra® injection include all of those associated with Keppra® tablets and oral solution. US prescribing information is available at

http://www.ucb.com/_up/ucb_com_products/documents/Keppra_Labeling_12_2011.pdf
http://www.ucb.com/_up/ucb_com_products/documents/Keppra_%20Injection_COL_%208E_%2006_2011.pdf

Keppra® in the European Union – Important Safety Information
Contraindication: Keppra® is contraindicated in patients with hypersensitivity to levetiracetam or other pyrrolidone derivatives or any of the excipients. Special warnings and precautions for use: In accordance with clinical practice if Keppra® has to be discontinued it is recommended to withdraw it gradually. The administration of Keppra® to patients with renal impairment may require dose adjustment. In patients with severely impaired hepatic function, assessment of renal function is recommended before dose selection. Suicide, suicide attempt and suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents (including levetiracetam). Patients should be monitored for signs or depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Undesirable effects: The adverse event profile presented below is based on the analysis of pooled placebo-controlled clinical trials with all indications studied, with a total of 3,416 patients treated with levetiracetam. These data are supplemented with the use of levetiracetam in corresponding open-label extension studies, as well as post-marketing experience. The most frequently reported adverse reactions were nasopharyngitis, somnolence, headache, fatigue and dizziness. The safety profile of levetiracetam is generally similar across age groups (adults and paediatric patients) and across the approved epilepsy indications.

Adverse reactions (very common and common) reported in clinical studies (adults, adolescents, and children and infants >1 month) and from post-marketing experience are listed below. Very common undesirable effects (frequency ≥1/10): nervous system disorders – somnolence and headache; infections and infestations - nasopharyngitis. Common undesirable effects (frequency ≥1/100, <1/10): General disorders and administration site conditions - asthenia/fatigue; Nervous system disorders - convulsion, dizziness, tremor, balance disorder, lethargy; Psychiatric disorders - depression, hostility/aggression, insomnia, nervousness/irritability, anxiety; Gastrointestinal disorders - abdominal pain, diarrhoea, dyspepsia, nausea, vomiting; Metabolism and nutrition disorders - anorexia. The risk of anorexia is higher when topiramate is co-administered with levetiracetam; Ear and labyrinth disorders - vertigo; Respiratory, thoracic and mediastinal disorders - cough; Skin and subcutaneous tissue disorders - rash.

Please refer to the European summary of product characteristics for other adverse reactions and full prescribing and safety information. Date of last revision 24th October 2011 http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000277/WC500041334.pdf (Accessed 2nd January 2012)

About Vimpat®
In the U.S. Vimpat® tablets and injection were launched in May 2009 as an add-on therapy for the treatment of partial-onset seizures in people with epilepsy who are aged 17 years and older. Vimpat® injection is a short-term replacement when oral administration is not feasible in these patients. Vimpat® oral solution was launched in June 2010.

In the European Union, Vimpat® (film-coated tablets and solution for infusion) is approved as adjunctive therapy for the treatment of partial-onset seizures with or without secondary generalization in patients with epilepsy aged 16 years and older. Vimpat® solution for infusion may be used when oral administration is temporarily not feasible.

Vimpat® in the U.S. - Important Safety Information
AEDs increase the risk of suicidal behavior and ideation. Patients taking Vimpat® should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. The most common adverse reactions occurring in ≥10 percent of Vimpat®-treated patients, and greater than placebo, were dizziness, headache, nausea, and diplopia. For full prescribing information on Vimpat®, visit http://www.vimpat.com/prescribing-information.aspx (Accessed 18th October, 2011).
For more information on Vimpat®, visit www.Vimpat.com or contact UCB at (800) 477-7877. Vimpat® (C-V) is a Schedule V controlled substance.

Vimpat® in the EU and EEA - Important Safety Information
Contraindications: Hypersensitivity to the active substance or any of the excipients; known second- or third-degree atrioventricular (AV) block. Special warnings and precautions for use: Treatment with lacosamide has been associated with dizziness which could increase the occurrence of accidental injury or falls. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicine. Prolongations in PR interval with lacosamide have been observed in clinical studies. Lacosamide should be used with caution in patients with known conduction problems or severe cardiac disease such as a history of myocardial infarction or heart failure. Caution should especially be exerted when treating elderly patients as they may be at an increased risk of cardiac disorders or when lacosamide is used in combination with products known to be associated with PR prolongation. Second-degree or higher AV block has been reported in post-marketing experience. In the placebo-controlled trials of lacosamide in epilepsy patients, atrial fibrillation or flutter were not reported; however, both have been reported in open-label epilepsy trials and in post-marketing experience. Patients should be made aware of the symptoms of second-degree or higher AV block (e.g. slow or irregular pulse, feeling of lightheadedness and fainting) and of the symptoms of atrial fibrillation and flutter (e.g. palpitations, rapid or irregular pulse, shortness of breath). Patients should be counseled to seek medical advice should any of these symptoms occur. Suicidal ideation and behavior have been reported in patients treated with antiepileptic agents. Therefore patients should be monitored for signs of suicidal ideation and behaviors and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behavior emerge. The solution for infusion contains sodium, which should be taken into consideration for patients on a controlled sodium diet. Effects on ability to drive and use machines: Lacosamide may have minor to moderate influence on the ability to drive and use machines. Lacosamide treatment has been associated with dizziness or blurred vision. Accordingly patients should be advised not to drive a car or to operate other potentially hazardous machinery until they are familiar with the effects of lacosamide on their ability to perform such activities. Laboratory abnormalities: Abnormalities in liver function tests have been observed in controlled trials with lacosamide in adult patients with partial-onset seizures who were taking 1-3 concomitant antiepileptic drugs. Elevations of ALT to ≥3XULN occurred in 0.7% (7/935) of lacosamide patients and 0% (0/356) of placebo patients. Multiorgan Hypersensitivity Reactions: Multiorgan hypersensitivity reactions have been reported in patients treated with some antiepileptic agents. These reactions are variable in expression but typically present with fever and rash and can be associated with involvement of different organ systems. Potential cases have been reported rarely with lacosamide and if multiorgan hypersensitivity reaction is suspected, lacosamide should be discontinued. Undesirable effects: The most common adverse reactions (≥10%) are dizziness, headache, diplopia, and nausea. Other common adverse reactions (≥1%<10%) are depression, confusional state, insomnia, balance disorder, coordination abnormal, memory impairment, cognitive disorder, somnolence, tremor, nystagmus, hypoesthesia, dysarthria, disturbance in attention, vision blurred, vertigo, tinnitus, vomiting, constipation, flatulence, dyspepsia, dry mouth, pruritus, rash, muscle spasms, gait disturbance, asthenia, fatigue, irritability, injection site pain or discomfort (specific to solution for infusion), irritation (specific to solution for infusion), fall, and skin laceration. Refer to the European Summary of Product Characteristics for other adverse reactions and full prescribing information. Date of revision: 24 November, 2011.

http://ec.europa.eu/health/documents/community-register/html/h470.htm (Accessed 5th January 2012)

Reference
Pina Garza, E-G et al. (2009) Adjunctive levetiracetam in infants and young children with refractory partial-onset seizures Epilepsia, 50(5):1141–1149

For further information
Antje Witte, Investor Relations UCB
T +32.2.559.9414, antje.witte@ucb.com
France Nivelle, Global Communications, UCB
T +32.2.559.9178, france.nivelle@ucb.com
Eimear O Brien, Director, Brand Communications, UCB
T +32.2.559.9271, eimear.obrien@ucb.com
Kristie Madara, U.S. Corporate Communications, UCB
T + 1 (770) 970-8726, kristie.madara@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 more than 8 500 people in about 40 countries, the company generated revenue of EUR 3.2 billion in 2010. UCB is listed on Euronext Brussels (symbol: UCB).

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