Three-Year Data From Sabril® (vigabatrin) Registry Presented at American Epilepsy Society Annual Meeting

  Three-Year Data From Sabril® (vigabatrin) Registry Presented at American
  Epilepsy Society Annual Meeting

Business Wire

SAN DIEGO -- December 03, 2012

Three-year vision data from Lundbeck’s Sabril (vigabatrin) patient registry
were presented as a late-breaking poster presentation at the annual meeting of
the American Epilepsy Society (AES). The data set includes 4,292 patients
enrolled as of August 22, 2012.^1 The U.S. Food and Drug Administration (FDA)
requires a Risk Evaluation and Mitigation Strategy (REMS) because of the risk
of Sabril-induced permanent vision loss, and includes an ongoing patient
registry.

Sabril is indicated as adjunctive therapy for adult patients with refractory
complex partial seizures (CPS) who have inadequately responded to several
alternative treatments and for whom the potential benefits outweigh the risk
of vision loss. Sabril is not indicated as a first-line agent for complex
partial seizures. ^ 2 Sabril is indicated as monotherapy for pediatric
patients 1 month to 2 years of age with infantile spasms (IS) for whom the
potential benefits outweigh the potential risk of vision loss.^3

Of the total patients enrolled in the registry, 2,676 had IS and 1,354 had
refractory CPS.^1 Because of the nature of the registry and vision testing
variability, particularly among IS patients, a clear comparison cannot be
drawn between registry data and clinical trial results.^1

“Continued analyses of this data allow us to further our knowledge of Sabril,
its potential benefits and the risk of permanent vision loss,” said Robert C.
Sergott, MD, lead author of the poster, director of neuro-ophthalmology at the
Wills Eye Institute, and professor of ophthalmology, neurology and
neurosurgery at Thomas Jefferson University Medical College. Dr. Sergott is
also one of two expert neuro-opthalmologists who are part of the Sabril
registry steering committee and who reviewed detailed vision test findings for
technical adequacy and clinical significance. He added, “This registry data
sheds light on Sabril use since it became available in the U.S. in 2009,
including the number of patients who have received the therapy. It also
reports why patients have discontinued Sabril use for reasons including
completion of therapy, physician or patient choice, or vision loss clarified
as a visual field defect.”

A data subset of 718 patients with 1,125 sets of cumulative detailed vision
results reviewed by the neuro-ophthalmologists were also included in the
poster presentation.^1 This subset included all patients who voluntarily
submitted vision results for expert analysis.

“Refractory complex partial seizures and infantile spasms present patients,
their caregivers and physicians with numerous challenges, and considerations
about potential adverse events associated with a particular medicine are just
as important as a therapy’s potential benefits,” said John M. Pellock, MD, an
author on the poster presentation and chairman of the Division of Child
Neurology and professor of neurology, pediatrics and pharmacy and
pharmaceutics at Virginia Commonwealth University. “This prospective,
longitudinal Sabril data provide physicians with more information as they work
with their patients to make informed choices.”

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 Sabril Registry

All patients using Sabril are enrolled in a registry. The registry collects
prescriber specialty, patient demographics, diagnosis, prior and concurrent
anti-seizure medications, periodic ophthalmologic assessment data (i.e., the
results of mandatory monitoring every three months), and the proportion of
patients receiving Sabril for rCPS and IS who respond/do not respond to Sabril
during the treatment initiation phase.

About Infantile Spasms

Infantile spasms is a difficult-to-treat epilepsy syndrome that usually
strikes infants between four to eight months old.^4 Infants suffer spasms that
typically last for one to five seconds^5 and occur in clusters of up to 100
spasms at a time.^4 An estimated 8,500 infants in the U.S. have been diagnosed
with IS,^6 and each year approximately 2,500 new cases of IS are reported in
the U.S. Sabril may not be appropriate for use in all patients with IS.

About Complex Partial Seizures

There are more than two million Americans (AP) affected by epilepsy,^7 and
approximately 35 percent have CPS,^8 the single largest seizure type, which
originates from a single region of the brain and can cause impaired
consciousness.^8 Despite the availability of many antiepileptic treatment
options, approximately 30 to 36 percent of adults with CPS continue to have
seizures.^9,10,11

About Sabril® (vigabatrin)^2,3

Sabril is an oral antiepileptic drug developed in the United States by
Lundbeck. Sabril is available in two formulations — in 500-mg tablets for use
as add-on therapy for adults with refractory CPS and in 500-mg packets of
powder for oral solution for infants with IS.

Indication

SABRIL is indicated as adjunctive therapy for adult patients with refractory
complex partial seizures (CPS) who have inadequately responded to several
alternative treatments and for whom the potential benefits outweigh the risk
of vision loss. SABRIL is not indicated as a first line agent for complex
partial seizures.

SABRIL is indicated as monotherapy for pediatric patients 1 month to 2 years
of age with infantile spasms (IS) for whom the potential benefits outweigh the
potential risk of vision loss.

Important Safety Information

                             WARNING: VISION LOSS

         See full Prescribing Information for complete boxed warning

  *SABRIL causes progressive and permanent bilateral concentric visual field
    constriction in a high percentage of patients. In some cases, SABRIL may
    also reduce visual acuity.
  *Risk increases with total dose and duration of use, but no exposure to
    SABRIL is known that is free of risk of vision loss
  *Risk of new and worsening vision loss continues as long as SABRIL is used,
    and possibly after discontinuing SABRIL
  *Unless a patient is formally exempted, periodic vision assessment is
    required for patients on SABRIL. However, this assessment cannot always
    prevent vision damage
  *Because of the risk of permanent vision loss, SABRIL is available only
    through a special restricted distribution program

SABRIL causes permanent vision loss in infants, children, and adults. Because
assessing vision loss is difficult in children, the frequency and extent of
vision loss in infants and children is poorly characterized.

In adults, SABRIL causes permanent bilateral concentric visual field
constriction in 30% or more of patients that ranges in severity from mild to
severe, including tunnel vision to within 10° of visual fixation, and can
result in disability. In some cases, SABRIL also can damage the central retina
and may decrease visual acuity. The onset of vision loss from SABRIL is
unpredictable and can occur within weeks of starting treatment or sooner, or
at any time during treatment, even after months or years. The lowest dose and
shortest exposure to SABRIL should be used that is consistent with clinical
objectives.

Because of the risk of permanent vision loss, SABRIL should be withdrawn from
patients with IS who fail to show substantial clinical benefit within 2 to 4
weeks of initiation, or sooner if treatment failure becomes obvious, or adult
patients treated for refractory CPS as adjunctive therapy who fail to show
substantial clinical benefit within 3 months of initiation, or sooner if
treatment failure becomes obvious. Patient response to and continued need for
SABRIL should be periodically reassessed.

Unless a patient is formally exempted from periodic ophthalmologic assessment
as documented in the SHARE program, vision assessment is required at baseline
(no later than 4 weeks after starting SABRIL), at least every 3 months while
on therapy and about 3-6 months after the discontinuation of SABRIL therapy.
Once detected, vision loss is not reversible. It is expected that, even with
frequent monitoring, some patients will develop severe vision loss. Drug
discontinuation should be considered, balancing benefit and risk, if visual
loss is documented.

Symptoms of vision loss from SABRIL are unlikely to be recognized by the
patient, parent or caregiver before vision loss is severe. Vision loss of
milder severity, although unrecognized by the patient, parent or caregiver may
still adversely affect function. The possibility that vision loss from SABRIL
may be more common, more severe, or have more severe functional consequences
in infants and children than in adults, cannot be excluded.

SABRIL should not be used in patients with, or at high risk of, other types of
irreversible vision loss or with other drugs associated with serious adverse
ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly
outweigh the risks. The interaction of other types of irreversible vision
damage with vision damage from SABRIL has not been well characterized, but is
likely adverse.

In adult patients treated for CPS, dose adjustment is necessary in patients
with renal impairment.

Abnormal MRI signal changes have been observed in some infants treated for IS
with SABRIL. These changes generally resolved with discontinuation of
treatment and in a few patients the lesion resolved despite continued use.

Antiepileptic drugs (AEDs), including SABRIL, increase the risk of suicidal
thoughts or behavior. Adult patients should be monitored for the emergence or
worsening of depression, suicidal thoughts or behavior and/or any unusual
changes in mood or behavior.

As with all AEDs, SABRIL should be discontinued gradually to avoid withdrawal
seizures.

Vigabatrin is excreted in human milk and may cause serious adverse events in
nursing infants. SABRIL should not be used during pregnancy unless the
potential benefit justifies the potential risk to the fetus. Pregnancy
Registry: To provide information regarding the effects of in utero exposure to
SABRIL, physicians are advised to recommend that pregnant patients taking
SABRIL enroll in the North American Antiepileptic Drug (NAAED) Pregnancy
Registry. This can be done by calling the toll-free number 1-888-233-2334, and
must be done by patients themselves. Information on the registry can also be
found at the website http://www.aedpregnancyregistry.org/.

SABRIL has been shown to cause neurotoxicity, anemia, somnolence and fatigue,
peripheral neuropathy, weight gain and edema. The most commonly observed
adverse reactions reported in 2 add-on clinical studies of adults with
refractory CPS treated with SABRIL as adjunctive therapy with the recommended
dose of 3 g/day (≥10% and at least 5% greater than placebo, respectively) were
dizziness (24% vs 17%), fatigue (23% vs 16%), somnolence (22% vs 13%), tremor
(15% vs 8%), blurred vision (13% vs 5%), and arthralgia (10% vs 3%). A 6 g/day
dose has not been shown to confer additional benefit compared to the 3 g/day
dose and is associated with an increased incidence of adverse events.

The most common adverse events reported by >5% of infants taking SABRIL for IS
occurring more frequently than placebo, respectively, in a randomized,
placebo-controlled IS study with a 5-day double-blind treatment phase (n=40)
were somnolence (45% vs 30%), bronchitis (30% vs 15%), ear infection (10% vs
5%), and acute otitis media (10% vs 0%).

Oral Solution: For more information, please see the full Prescribing
Information including Boxed Warning, Medication Guide and Dosing Instructions.

Solución oral: Para más información, vea por favor la información que
prescribe completa incluyendo la advertencia encajonada, guía de la medicación
y las instrucciones de la dosificación.

Tablets: For more information, please see the full Prescribing Information
including Boxed Warning and Medication Guide.

Tabletas: Para más información, vea por favor la información que prescribe
completa incluyendo la advertencia encajonada y guía de la medicación.

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.

Sources

1.AES Late-Breaker 2012.
2.Sabril® (vigabatrin) Tablets Full Prescribing Information. Deerfield, IL:
    Lundbeck Inc. 2011.
3.Sabril® (vigabatrin) Oral Solution Full Prescribing Information.
    Deerfield, IL: Lundbeck Inc. 2011.
4.National Institute of Neurological Disorders and Stroke. NINDS Infantile
    Spasms Information Page.
    http://www.ninds.nih.gov/disorders/infantilespasms/infantilespasms.htm.
    Last visited 11/14/12.
5.Holmes, Gregory. Epilepsy.com. Infantile Spasms. 2006.
    http://www.epilepsy.com/epilepsy/epilepsy_infantilespasms. Last accessed
    11/14/12.
6.Hurst D. The epidemiology of infantile spasms. In: Dulac O, Chugani H.
    Dalla Bernardina B., eds. Infantile Spasms and West Syndrome.
    Philadelphia, PA: Saunders; 1994.
7.Epilepsy Foundation. About Epilepsy: Statistics.
    http://www.epilepsyfoundation.org/aboutepilepsy/index.cfm/statistics. Last
    accessed 11/14/12.
8.Carroll, Elizabeth. Medscape. Complex Partial Seizures.
    http://emedicine.medscape.com/article/1183962-overview. Last visited
    11/22/11.
9.Kwan P, Brodie MJ. Early identification of refractory epilepsy. New
    England Journal of Medicine. February 3, 2000; 342:314-319.
10.Devinsky O. Patients with refractory seizures. New England Journal of
    Medicine. May 20, 1999;340:1565-70.
11.Rielo, Diego M. Medscape. Vagus Nerve Stimulation. 2011.
    http://emedicine.medscape.com/article/1186123-overview. Last accessed
    11/14/12.

Contact:

Lundbeck
Matt Flesch, (847) 922-2871
 
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