Results of Long-Term, Open-Label Extension Study Evaluating ONFI® (clobazam) CIV Presented at American Epilepsy Society Annual

  Results of Long-Term, Open-Label Extension Study Evaluating ONFI® (clobazam)
  CIV Presented at American Epilepsy Society Annual Meeting

   Longest and largest study of an AED in LGS assessed safety and efficacy
                              through six years

Late-breaker presentation at AES focuses on data in patients who received ONFI
                               for three years

Business Wire

SAN DIEGO -- December 03, 2012

Data from a long-term, open-label extension study (OLE) evaluating ONFI
(clobazam) Tablets CIV for the adjunctive treatment of drop seizures
associated with Lennox-Gastaut syndrome (LGS) were presented as a
late-breaking poster at the annual meeting of the American Epilepsy Society
(AES).^1 A 1,5-benzodiazepine, ONFI was approved by the U.S. Food and Drug
Administration (FDA) in 2011 for the adjunctive treatment of seizures
associated with LGS in adults and children as young as two.^2

This study enrolled patients with a current or previous diagnosis of LGS aged
2 to 60 years old. Patients had previously completed one of two double-blind
clinical trials evaluating ONFI as adjunctive therapy for drop seizures
associated with LGS, and qualifying patients were given the option of tapering
off ONFI or continuing in the OLE. Of 306 patients previously enrolled in
these two earlier studies, 267 entered the OLE during the enrollment period of
Dec. 28, 2005 through Dec. 15, 2009. Approximately 70 percent (188 of 267) of
these patients remained in the study until its conclusion on March 23, 2012.^1

The primary efficacy endpoint of the study was median percentage decrease in
average weekly rate of drop seizures measured at eight separate time points
from month 3 through three years, compared with last assessment before first
dose of ONFI. Results from this endpoint include 113 patients who received
ONFI for three years.^1 Further results for those patients who received ONFI
for greater than three years are expected to be published during 2013.

“While LGS represents a small percentage of patients an epilepsy specialist
typically treats, the diagnosis often requires a significant amount of time,
resources and attention because of the frequency and severity of seizures,”
said Yu-tze Ng, director of epilepsy at the University of Oklahoma College of
Medicine and lead investigator of the study. “It’s important to collect
long-term data because these challenging seizures associated with LGS
typically continue throughout the patient’s life.”

LGS is a rare and severe form of epilepsy that is typically diagnosed in
childhood and often persists into adulthood.^4,5,6 LGS is associated with
multiple types of seizures with periods of frequent seizures, and daily
seizures are common.^7 Some of these seizures, including atonic, tonic and
myoclonic seizures, may cause falls and are called “drop seizures” (also
referred to as “drop attacks”), which may result in injury.^8

“There is no quick fix for LGS. The diagnosis takes patients, their families
and health care teams on a long-term journey from childhood diagnosis into the
adult years, from one seizure type to the next, while multiple AEDs are used
to manage the condition,” said Juliann Paolicchi, MD, director of the
pediatric comprehensive epilepsy program at Weill Cornell Medical Collegein
New York, as well as co-investigator of the study. “We are pleased that
Lundbeck was able to partner with a group of clinical researchers to
investigate the use of ONFI for this difficult to treat disorder.”

The most common adverse events experienced in this OLE (≥15%) included upper
respiratory infection, pyrexia, somnolence, pneumonia, fall and otitis media.
A total of 79 (29.6%) patients discontinued the study for the following
reasons: patient/parent/caregiver request (33 patients), lack of efficacy
(15), adverse events (10), death (9) and “other reasons” (12).^1

About the Presentation

This study was presented at AES on Saturday, Dec. 1, 11:45 a.m. – 1:45 p.m.,
during Poster Session 1 at the San Diego Convention Center in Hall B, Ground
Level.

About the Study

This multicenter, open-label extension study of ONFI (clobazam) was designed
to assess the long-term safety and efficacy of open-label ONFI as adjunctive
therapy for patients with seizures associated with LGS. The study included 267
qualifying patients who had completed one of two randomized controlled trials
– a Phase II dose-ranging study (N=68) or a pivotal Phase III study (N=238;
CONTAIN Trial).^1

Patients were eligible to continue on to the open-label study if no more than
14 days elapsed since their last dose in the dose-ranging study (Phase II) or
the CONTAIN Trial.^1 For patients from the CONTAIN Trial, ONFI was started at
a target dosage of 0.5 mg/kg/day (maximum 40 mg/day). This dosage was
maintained for 48 hours, and thereafter adjusted per clinical need. For
patients from the dose-ranging study who chose to continue in the open-label
study, the unblinded physician adjusted or maintained the dosage the patient
was previously receiving. ^ 1

About ONFI^® (clobazam) Tablets CIV

ONFI is an oral antiepileptic drug developed in the United States by Lundbeck,
and is available in 5-mg, 10-mg, and 20-mg tablets. ONFI is a
1,5-benzodiazepine.^2 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
GABA[A ]receptor.^9

Indication

ONFI is indicated for the adjunctive treatment of seizures associated with
Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.

Important Safety Information

  *ONFI causes somnolence and sedation. In clinical trials, somnolence or
    sedation were reported at all effective doses and were dose-related. In
    general, somnolence and sedation begin within the first month of treatment
    and may diminish with continued treatment. Prescribers should monitor
    patients for somnolence and sedation, particularly with concomitant use of
    other central nervous system (CNS) depressants. Prescribers should caution
    patients against engaging in hazardous activities requiring mental
    alertness, such as operating dangerous machinery or motor vehicles, until
    the effect of ONFI is known.
  *ONFI has a CNS depressant effect. Patients should be cautioned against the
    simultaneous use with other CNS depressant drugs or alcohol, and cautioned
    that the effects of other CNS depressant drugs or alcohol may be
    potentiated.
  *As with all Antiepileptic drugs (AEDs), ONFI should be gradually withdrawn
    to minimize the risk of precipitating seizures, seizure exacerbation or
    status epilepticus. Withdrawal symptoms have been reported following
    abrupt discontinuation of ONFI; the risk of withdrawal symptoms is greater
    with higher doses.
  *Patients with a history of substance abuse should be under careful
    surveillance when receiving ONFI or other psychotropic agents because of
    the predisposition of such patients to habituation and dependence. In
    clinical trials, cases of dependency were reported following abrupt
    discontinuation of ONFI. The risk of dependence increases with increasing
    dose and duration of treatment.
  *AEDs including ONFI increase the risk of suicidal thoughts or behavior in
    patients. Patients, their caregivers, and families should be informed of
    the risk and advised to monitor and report any emergence or worsening of
    depression, suicidal thoughts or behavior, or any unusual changes in mood
    or behavior, or thoughts of self-harm. If these symptoms occur, consider
    if it may be related to the AED or illness because epilepsy itself can
    increase these risks.
  *The most commonly observed adverse reactions reported in an LGS
    randomized, double-blind placebo-controlled, parallel group clinical trial
    who received clobazam as adjunctive therapy (≥10% in any treatment group;
    low, medium or high dose and at least 5% greater than placebo
    respectively) were somnolence or sedation (32% vs. 15%), somnolence (25%
    vs. 12%), pyrexia (17% vs. 3%), lethargy (15% vs. 5%), drooling (14% vs.
    3%), aggression (14% vs. 5%), irritability (11% vs. 5%), ataxia (10% vs.
    3%) and constipation (10% vs. 0%).

For more information, please see the ONFI full Prescribing Information and
Medication Guide.

About Lundbeck in the U.S.

A wholly-owned subsidiary of H. Lundbeck A/S, Lundbeck in the U.S. is
headquartered in Deerfield, Illinois,and is committed to accelerating our
work in central nervous system (CNS) disorders, including challenging seizure
disorders. Additionally, Lundbeck employees actively support and participate
in hundreds of epilepsy awareness events each year as part of their ongoing
commitment to make a difference for those impacted by epilepsy. For more
information, please visit lundbeckus.com.

About Lundbeck

H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is an international pharmaceutical
company highly committed to improving the quality of life for people suffering
from psychiatric and neurological 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, psychotic disorders, 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 6,000 people worldwide. Lundbeck is one of the
world's leading pharmaceutical companies working with psychiatric and
neurological disorders. In 2011, the company's revenue was DKK 16.0 billion
(approximately EUR 2.2 billion or USD 3.0 billion). For more information,
please visit www.lundbeck.com.

ONFI is a registered trademark of Lundbeck.

Sources

1. AES Late-Breaker 2012.

2. ONFI Full Prescribing Information. Deerfield,IL: Lundbeck Inc. October
2011.

3. Ng YT, Conry JA, Drummond R, Stolle J, Weinberg M, on behalf of the OV-1012
Study Investigators. Randomized, phase III study results of clobazam in
Lennox-Gastaut Syndrome. Neurology. 2011;77:1473–81.

4. Van Rijckevorsel, Kenou et al. Treatment of Lennox-Gastaut syndrome:
overview and recent findings. Neuropsychiatric Disease and Treatment. 2008:
4(6) 1001-1019.

5. Arzimanoglou, Alexis et al. Lennox-Gastaut syndrome: a consensus approach
on diagnosis, assessment, management, and trial methodology. The Lancet. 2009:
8(1) 82-93.

6. Cherian, K. Lennox-Gastaut Syndrome. Medscape. 2012.
http://emedicine.medscape.com/article/1176735-overview. Last accessed
11/14/12.

7. Borggraefe I, Noachtar S. Pharmacotherapy of Seizures Associated with
Lennox-Gastaut Syndrome. Clinical Medicine Insights: Therapeutics. 2010:2
15-24.

8. Dulac, O, Engel, J. Lennox-Gastaut Sydnrome. International League Against
Epilepsy. http://www.ilae-epilepsy.org/Visitors/Centre/ctf/lennox_gastaut.cfm.
Last accessed 9/16/11.

9. Sankar R. GABAA Receptor Physiology and its Relationship to the Mechanism
of Action of the 1,5-Benzodiazepine Clobazam. CNS Drugs. 2012;26:229–44.

Contact:

Lundbeck
Matt Flesch, (847) 922-2871
 
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