FDA approves Onfi™ (clobazam) for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome

• Onfi™ now approved for Lennox-Gastaut syndrome a rare orphan epilepsy disorder
• Lennox-Gastaut syndrome is one of the most severe forms of epilepsy and there is a clear need for new treatment options
• Onfi™ has the potential to contribute to Lundbeck's growth opportunities in the years to come

H. Lundbeck A/S (Lundbeck) announced today that the US Food and Drug Administration (FDA) has approved Onfi™ (clobazam) as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS) in patients two years and older¹. Onfi™ (pronounced “ON-fee”) will be available in US pharmacies in early January 2012 and is a federally controlled schedule four substance (C-IV). 

LGS is a rare and severe form of epilepsy that is typically diagnosed in childhood and often persists into adulthood^2,3,4. LGS is associated with multiple types of seizures with periods of frequent seizures, and daily seizures are common⁵. Some of these seizures, including atonic, tonic and myoclonic seizures, may cause falls, or “drop seizures” (also referred to as “drop attacks”), which may result in injury⁶.

The FDA approval of Onfi™ was based on two multicenter controled studies similar in terms of disease characteristics and prior treatment of patients, including a pivotal phase III clinical study in 238 patients with a current or prior diagnosis of LGS. Named the CONTAIN Trial, the study’s primary endpoint was the percent reduction in the weekly frequency drop seizures (atonic, tonic, or myoclonic) from the 4-week baseline period compared to the 12-week maintenance period. A Phase II dose-ranging study was also conducted (n=68) that was consistent with results of the CONTAIN Trial.¹

"We are pleased with the FDA approval of Onfi™ as it represents yet another milestone for Lundbeck in the US and for our continued efforts to develop new business opportunities for the benefit of patients as well as the company," says Executive Vice President Anders Gersel Pedersen, Head of R&D at Lundbeck, and continues: "Onfi™ has in the largest clinical study ever conducted in LGS patients showed very solid clinical data which was further supported by several key secondary efficacy endpoints.”

The most common adverse reactions in the CONTAIN Trial included sleepiness or tiredness, fever, drooling, acting aggressive, irritability, lack of coordination and constipation.¹ The adverse reactions leading to discontinuation in ≥ 1 percent in the CONTAIN trial in decreasing order of frequency included tiredness, sleepiness, lack of coordination, acting aggressive, fatigue and difficulty sleeping.¹

In conjunction with approval of the LGS indication, and as a result of the FDA's orphan designation for Onfi™ in the treatment of LGS, the FDA has also granted Onfi™ a seven-year exclusivity period during which the FDA is prohibited from approving any other formulation for LGS unless the other formulation is demonstrated to be clinically superior to Onfi™.

About Onfi™ (clobazam)
Onfi™ is an oral antiepileptic drug developed in the United States by Lundbeck, and will be available in 5 mg, 10 mg, and 20 mg tablets¹. Onfi™ is a 1,5 benzodiazapene. The exact mechanism of action for Onfi™ is not fully understood, but is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABAA receptor.

Important Safety Information

• Onfi is a prescription medicine used along with other medicines to treat seizures associated with Lennox-Gastaut syndrome in people 2 years of age or older.
• Onfi™ can make you sleepy or dizzy and can slow your thinking and make you clumsy which may get better over time. Do not drive, operate heavy machinery, or other dangerous activities until you know how Onfi™ affects you. Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking Onfi™ without first talking to your healthcare provider as your sleepiness or dizziness may get much worse.
• Onfi™ can cause withdrawal symptoms. Do not stop suddenly taking ONFI without first talking to a healthcare provider. Stopping Onfi™ suddenly can cause seizures that will not stop (status epilepticus), hearing or seeing things that are not there (hallucinations), shaking, nervousness, and stomach and muscle cramps.
• Onfi™ can be abused and cause dependence.  Physical dependence is not the same as drug addiction. Talk to your healthcare provider about the differences. Onfi™ is a federally controlled substance (C-IV) because it can be abused or lead to dependence. 
• Like other antiepileptic drugs, Onfi™ may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Call your healthcare provider right away if you have any symptoms, especially sudden changes in mood, behaviors, thoughts, or feelings, and especially if they are new, worse, or worry you.
• If you are pregnant or plan to become pregnant, Onfi™ may harm your unborn baby.  You and your healthcare provider will have to decide if you should take Onfi^TM while you are pregnant.
• Onfi™ can pass into breast milk. You and your healthcare provider should decide if you should take Onfi™ or breast feed.  You should not do both. 
• The most common side effects seen in Onfi™ patients include: sleepiness;  drooling; constipation; cough; pain with urination; fever; acting aggressive, being angry or violent; difficulty sleeping; slurred speech; tiredness and problems with breathing.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

For more information and to see full Prescribing Information including Medication Guide go to www.LundbeckInc.com.

About Lennox-Gastaut Syndrome
Lennox-Gastaut syndrome (LGS) is a rare and severe form of epilepsy characterized by multiple types of seizures, mental retardation or regression, and abnormal electroencephalogram (EEG) with generalized slow spike and wave discharges (1.5-2 Hz)^{2, 4, 8}. Responsible for 1-4 percent of all childhood epilepsies⁸, LGS typically occurs between two and eight years of age (peak onset occurs from 3-5 years)². Eighty percent of those with LGS will have continued seizures throughout childhood and into their adult years³. LGS is associated with multiple seizure types, including atonic, tonic and myoclonic seizures, which can all cause falls, or "drop seizures", that are associated with a high rate of recurrent injuries⁶. Prognosis for individuals with LGS varies, and complete recovery, including freedom from seizures and normal development, is uncommon⁴.

Sources

1. Onfi^TM Full Prescribing Information. Deerfield, IL: Lundbeck Inc. October 2011.
2. Van Rijckevorsel, Kenou et al. Treatment of Lennox-Gastaut syndrome: overview and recent findings. Neuropsychiatric Disease and Treatment. 2008: 4(6) 1001-1019.
3. Arzimanoglou, Alexis et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. The Lancet. 2009: 8(1) 82-93.
4. NINDS. Lennox-Gastaut Syndrome Information Page. http://www.ninds.nih.gov/disorders/lennoxgastautsyndrome/lennoxgastautsyndrome.htm. Last accessed 9/16/11.
5. Borggraefe I, Noachtar S. Pharmacotherapy of Seizures Associated with Lennox-Gastaut Syndrome. Clinical Medicine Insights: Therapeutics. 2010:2 15-24.
6. Dulac, Olivier and Jerome Engel. Lennox-Gastaut Sydnrome. International League Against Epilepsy. http://www.ilae-epilepsy.org/Visitors/Centre/ctf/lennox_gastaut.cfm. Last accessed 9/16/11.
7. Hancock, Eleanor and Helen Cross. “Treatment of Lennox-Gastaut syndrome.” Cochrane Collaboration 2009.
8. Medscape. Lennox-Gastaut Syndrome. http://emedicine.medscape.com/article/1176735-overview. Last accessed 10/11/10

Financial guidance
The content of this release will have no influence on the Lundbeck Group's financial guidance for 2011 which was provided on 24 February 2011 in connection with the release of the financial results for 2010.

Lundbeck contacts

About Lundbeck

H. Lundbeck A/S (LUN.CO, LUN DC, HLUKY) is an international pharmaceutical company highly committed to improving the quality of life for people suffering from central nervous system (CNS) disorders. For this purpose, Lundbeck is engaged in the research, development, production, marketing and sale of pharmaceuticals across the world. The company’s products are targeted at disorders such as depression and anxiety, schizophrenia, insomnia, epilepsy and Huntington’s, Alzheimer’s and Parkinson’s diseases.

Lundbeck was founded in 1915 by Hans Lundbeck in Copenhagen, Denmark. Today Lundbeck employs approximately 5,900 people worldwide. Lundbeck is one of the world’s leading pharmaceutical companies working with CNS disorders. In 2010, the company's revenue was DKK 14.8 billion (approximately EUR 2.0 billion or USD 2.6 billion). For more information, please visit www.lundbeck.com.

Onfi™ is a trademark of Lundbeck Inc.