Post-Hoc Analysis of Open-Label Extension Study Assesses the Use of ONFI® (Clobazam) CIV and the Potential for Tolerance

DEERFIELD, Ill.–(BUSINESS WIRE)–Results from a post-hoc analysis of an open-label extension (OLE) study
evaluating the potential of developing tolerance to adjunctive ONFI
(clobazam) CIV in patients with Lennox-Gastaut syndrome (LGS) were
published online in Neurology. Tolerance can occur with repeated
administration of a medication – resulting in diminished efficacy and
the need for higher doses to maintain clinical effect. ONFI is a
benzodiazepine indicated for adjunctive treatment of seizures associated
with LGS in patients 2 years of age or older.

The post-hoc analysis was conducted to determine the change in mean
dosages over the first two years of the OLE (OV-1004) study based on
responder rates and baseline seizure quartiles in the Phase III lead-in
Study (OV-1012). A dosage increase of greater than or equal to 40
percent, plus loss of response, was defined as tolerance for individual
patients.

LGS is a severe epilepsy syndrome that can persist over many years, and
patients need treatment options that have demonstrated efficacy,” said
Barry Gidal, PharmD, University of Wisconsin School of Pharmacy & Dept.
of Neurology, and lead investigator of the post-hoc analyses. “One
question that many clinicians have is whether antiepileptic drug therapy
can lose effectiveness due to the development of pharmacologic
tolerance. This study is important because it is the first to examine
the potential of developing tolerance to ONFI.”

To read the full study, see the “Ahead
of Print”
section of the Neurology website. The study will
also be published in the upcoming October print issue of Neurology.

Lundbeck initially presented results from this study at the American
Epilepsy Society (AES) Annual Meeting in December, 2015.

About ONFI (clobazam) CIV

ONFI is an oral antiepileptic drug developed in the United States by
Lundbeck, and is available in 10 and 20 mg tablets, and as a 2.5 mg/mL
Oral Suspension. ONFI is a 1,5-benzodiazepine. 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.1

About Lennox-Gastaut syndrome

LGS is a rare and severe form of epilepsy that is typically diagnosed in
childhood and often persists into adulthood.2,3 LGS is
associated with multiple types of seizures, and daily seizures are
common.3 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 injury.2

Use

ONFI (clobazam) CIV 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.

Important Safety Information

  • Do not take ONFI if you have a known allergy to ONFI or its
    ingredients.
  • ONFI can make you sleepy or dizzy, slow your thinking, and make you
    clumsy which may get better over time. 
    Do not drive, operate
    heavy machinery, or do 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. ONFI may make your sleepiness or dizziness
    much worse.
  • ONFI can cause withdrawal symptoms. Do not suddenly stop 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
    (CIV) because it can be abused or lead to dependence.
  • Serious skin reactions have been seen with ONFI and may require
    stopping its use. 
    A serious skin reaction can happen at any
    time during your treatment with ONFI. Call your healthcare provider
    immediately if you have skin blisters, rash, sores in the mouth, hives
    or any other allergic reaction.
  • 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 of
    depression, especially sudden changes in mood, behaviors, thoughts, or
    feelings, and especially if they are new, worse, or worry you.
  • Tell your healthcare provider about all of your medical conditions
    including liver or kidney problems, lung problems (respiratory
    disease), depression, mood problems, or suicidal thoughts or behavior.
  • 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 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.
  • Tell your healthcare provider about all the medicines you take,
    including prescription and over-the-counter medicines, vitamins, and
    herbal supplements. Taking ONFI with certain other medicines can cause
    side effects or affect how well they work. ONFI may make your birth
    control medicine less effective. Talk to your healthcare provider
    about the best method to use. Do not start or stop ONFI or other
    medicines without talking to your healthcare provider.
  • ONFI oral suspension should be kept in its original bottle in an
    upright position and used within 90 days of first opening the bottle.
    After 90 days, safely throw away any unused ONFI oral suspension.
  • The most common side effects seen in patients taking ONFI include:
    sleepiness; drooling; constipation; cough; pain with urination; fever;
    acting aggressive, being angry or violent; difficulty sleeping;
    slurred speech; tiredness; and problems with breathing.

For more information, please see the full
Prescribing Information
Medication
Guide
, and Instructions
for Use
.

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.

ONFI is a registered trademark of Lundbeck.

About Lundbeck

Lundbeck is a global pharmaceutical company specialized in psychiatric
and neurological disorders. For more than 70 years, we have been at the
forefront of research within neuroscience. Our key areas of research
focus are depression, schizophrenia, Parkinson’s disease and Alzheimer’s
disease.

An estimated 700 million people worldwide are living with psychiatric
and neurological disorders and far too many suffer due to inadequate
treatment, discrimination, a reduced number of working days, early
retirement and other unnecessary consequences. Every day, we strive for
improved treatment and a better life for people living with psychiatric
and neurological disorders — we call this Progress in Mind.

Our approximately 5,000 employees in 55 countries are engaged in the
entire value chain throughout research, development, manufacturing,
marketing and sales. Our pipeline consists of several late-stage
development programs and our products are available in more than 100
countries. We have research centers in China and Denmark and production
facilities in China, Denmark, France and Italy. Lundbeck generated core
revenue of DKK 14.6 billion in 2015 (EUR 2 billion; USD 2.2 billion).

In the U.S., Lundbeck employs nearly 1,000 people focused solely on
accelerating therapies for brain disorders, including epilepsy. With a
special commitment to the lives of patients, families and caregivers,
Lundbeck U.S. actively engages in hundreds of initiatives each year that
support our patient communities.

For additional information, we encourage you to visit our corporate site www.lundbeckus.com
and connect with us on Twitter at @LundbeckUS.

Sources

1. 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.

2. Van Rijckevorsel K. Treatment of Lennox-Gastaut syndrome: Overview
and Recent Findings. Neuropsychiatric Disease and Treatment.
2008;4(6);1001‒1019.

3. Arzimanoglou A, French J, Blume WT, et al. Lennox-Gastaut syndrome: a
consensus approach on diagnosis, assessment, management, and trial
methodology. Lancet Neurology. 2009;8(1):82‒93.

CLB-C-00004

Contacts

Lundbeck
Rachel Vann, 224-507-8401
Public Relations, Senior
Manager
rvan@lundbeck.com

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