Sunovion Pharmaceuticals Inc. Presents Positive Results From Two Phase 3
Studies of Once-Daily Aptiom® (eslicarbazepine acetate) as Monotherapy
Treatment for Partial-Onset Seizures
*Patients with partial-onset seizures poorly-controlled on 1-2 AEDs who
converted to APTIOM monotherapy had a further 30.9%-47.5% reduction in
*Supplemental new drug application planned for spring 2014
MARLBOROUGH, Mass. -- December 9, 2013
Sunovion Pharmaceuticals Inc. (Sunovion) today announced results from two
Phase 3 trials (Studies 093-046 and 093-045) of Aptiom^® (eslicarbazepine
acetate) as a monotherapy treatment in patients with partial-onset seizures.
Study results showed that APTIOM demonstrated seizure control rates superior
to historical controls in patients with partial-onset seizures who were not
well-controlled by current antiepileptic drugs (AEDs). These data were
presented at the 67^th Annual Meeting of the American Epilepsy Society (AES)
taking place December 6-10 in Washington, D.C.
APTIOM was approved on November 8, 2013 by the U.S. Food and Drug
Administration (FDA) as adjunctive treatment of partial-onset seizures. The
efficacy and safety of APTIOM as monotherapy treatment for patients with
partial-onset seizures has not been evaluated by the FDA. APTIOM is not
approved for use as monotherapy.
“We are pleased with the data from these Phase 3 trials investigating APTIOM
as monotherapy treatment for adult patients with partial-onset seizures,” said
Fred Grossman, D.O., FAPA, Senior Vice President, Clinical Development and
Medical Affairs at Sunovion. “Based on the results of the data presented
today, Sunovion plans to seek approval of APTIOM as monotherapy treatment for
patients with partial-onset seizures.”
The objective of the studies was to evaluate the efficacy and safety of APTIOM
as monotherapy treatment for partial-onset seizures in patients who were not
well-controlled by current AEDs. The primary endpoint for both studies was the
proportion of patients with partial-onset seizures meeting pre-defined exit
criteria (signifying worsening seizure control) 16 weeks post-titration of
APTIOM, in comparison to historical controls. Treatment was considered
effective if the upper limit of the 95% confidence interval (CI) for the exit
rate (estimated using Kaplan-Meier methods) was lower than the lower limit of
the pre-specified prediction interval (i.e. 65.3% for a single study and 72.2%
for two independent studies), based on the historical controls.
Key Safety and Efficacy Results
The two completed Phase 3 APTIOM monotherapy trials (Studies 093-046 and
093-045) met their primary endpoints for both doses in each study. In Study
093-046, the exit rates (estimated using Kaplan-Meier methods) were 15.6% (95%
CI: 8.1 to 28.7%) for the 1,200 mg dose arm and 12.8% (95% CI: 7.5 to 21.5%)
for the 1,600 mg dose arm. In Study 093-045, the exit rates were 44.4% (95%
CI: 32.5 to 58.3%) for the 1,200 mg dose arm and 28.7% (95% CI: 21.2 to 38.1%)
for the 1,600 mg dose arm. For these studies, exit rates were lower than the
historical control thresholds of 65.3% (for a single study) and 72.2% (for two
independent studies). A pre-specified secondary endpoint of change from
baseline in standardized seizure frequency during the double-blind treatment
period demonstrated a median reduction in seizure frequency of 36.1% and 47.5%
in the 1,200 mg and 1,600 mg dose arms of Study 093-046, respectively, and
30.9% and 41.5% median reduction in seizure frequency in the 1,200 mg and
1,600 mg dose arms of Study 093-045, respectively.
APTIOM was well-tolerated in both monotherapy studies, with adverse events
generally similar to those observed in prior placebo-controlled adjunctive
trials. The most common treatment-emergent adverse events (TEAEs) in the two
studies were dizziness, headache, fatigue, somnolence, nausea and
nasopharyngitis, occurring in ≥5% of patients in both Studies 093-046 and
093-045. Additional TEAEs reported in Study 093-046 included back pain,
complex partial seizures, insomnia, anxiety and influenza. Additional TEAEs
reported in Study 093-045 included back pain, partial seizures with secondary
generalization, vomiting and blurred vision. In Study 093-046,
discontinuations due to TEAEs were reported in 3.4% and 12.3% of patients in
the 1,200 mg and 1,600 mg dose arms, respectively. Discontinuations due to
TEAEs were reported in 12.3% and 18.0% of subjects in the 1,200 mg and 1,600
mg dose arms, respectively, of Study 093-045. The TEAEs that most frequently
led to discontinuation seen in at least 2% of patients were complex partial
seizures (2.3%) in Study 093-046 and hyponatremia in Study 093-045 (2.1%).
Studies 093-046 and 093-045 were two Phase 3, double-blind,
historical-controlled, multicenter randomized trials with identical study
designs, which evaluated APTIOM monotherapy for treating partial-onset
seizures. Study 093-046, a global study, included 172 patients across 41 study
centers in five countries and included 25% of patients from the United States.
Study 093-045 included 193 patients from 67 study centers across North America
and is the first historically controlled epilepsy monotherapy study conducted
solely in North America.
In both studies, patients with partial-onset seizures 16 years of age or older
who were not well-controlled (≥ four partial-onset seizures in the eight weeks
prior to screening and no four week seizure-free period) with one to two AEDs
were gradually converted to monotherapy treatment with APTIOM and randomized
2:1 to receive APTIOM 1,600 mg once-daily (n=114 in Study 093-046; n=128 in
Study 093-045) or APTIOM 1,200 mg once-daily (n=58 in Study 093-046; n=65 in
Study 093-045). Patients with partial-onset seizures were using one AED (64.5%
in Study 093-046 and 73.6% in Study 093-045) or two AEDs (35.5% in Study
093-046 and 26.4% in Study 093-045).
About Partial-Onset Seizures
Epilepsy is characterized by abnormal firing of impulses from nerve cells in
the brain.^1 In partial-onset seizures, these bursts of electrical activity
are initially focused in specific areas of the brain, but may become more
widespread, with symptoms varying according to the affected areas.^2,3 The
unpredictable nature of seizures can have a significant impact on those with
epilepsy, affecting a number of areas of daily living, including education,
employment, driving and recreation.^4 Reducing the frequency of seizures can
greatly lessen the burden of epilepsy.^4 With approximately one-third of
people living with epilepsy still unable to control seizures, there continues
to be a need for new therapies.^5
APTIOM, a voltage-gated sodium channel inhibitor, is a prescription medicine
approved for use as adjunctive treatment of partial-onset seizures.
The initial research and development of eslicarbazepine acetate was performed
by BIAL-Portela & Ca, S.A. (BIAL), a privately held Portuguese research-based
pharmaceutical company. Subsequently, Sunovion acquired the rights under an
exclusive license to further develop and commercialize eslicarbazepine acetate
in the United States and Canadian markets from BIAL. BIAL gained approval for
eslicarbazepine acetate from the European Commission on April 21, 2009 as
adjunctive therapy in adult patients with partial-onset seizures with or
without secondary generalization and the agent is currently marketed under the
tradename Zebinix® in Europe under a license and co-promotion agreement with
Eisai Europe Limited, a European subsidiary of Eisai Co., Ltd.
Please see Important Safety Information below.
Sunovion Support™, the Sunovion patient assistance program, may help eligible
patients receive APTIOM at no charge to the patient when it becomes available.
Following the launch of APTIOM, more information on this program, including
eligibility criteria, may be found at www.SunovionSupport.com.
APTIOM (eslicarbazepine acetate) is a prescription medicine used with other
medicines to treat partial-onset seizures.
Important Safety Information
Do not take APTIOM if you are allergic to eslicarbazepine acetate, any of the
other ingredients in APTIOM or oxcarbazepine.
APTIOM may cause suicidal thoughts or actions, depression or mood problems.
Call your doctor right away if you experience these or any other effects or
APTIOM may cause serious skin rash or other serious allergic reactions, which
may affect organs or other parts of your body like the liver or blood cells.
Some symptoms may include: swelling of the face, eyes, lips or tongue, trouble
swallowing or breathing, yellowing of the skin or eyes or severe fatigue or
APTIOM may cause the level of sodium in your blood to be low. Symptoms may
include nausea, tiredness, lack of energy, irritability, confusion, muscle
weakness or muscle spasms, or more frequent or more severe seizures.
APTIOM may cause problems that can affect your nervous system including
dizziness, sleepiness, vision problems and difficulties with coordination and
APTIOM may slow your thinking or motor skills. Do not drive or operate heavy
machinery until you know how APTIOM affects you.
Do not stop taking APTIOM without first talking to your healthcare provider.
Stopping APTIOM suddenly can cause serious problems.
APTIOM may cause problems that can affect your liver. Symptoms of liver
problems include yellowing of your skin or the whites of your eyes and nausea
The most common side effects in patients taking APTIOM include dizziness,
sleepiness, nausea, headache, double vision, vomiting, feeling tired, problems
with coordination, blurred vision and shakiness.
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.
About Sunovion Pharmaceuticals Inc. (Sunovion)
Sunovion is a leading pharmaceutical company dedicated to discovering,
developing and commercializing therapeutic products that advance the science
of medicine in the Psychiatry & Neurology and Respiratory disease areas.
Sunovion’s drug development program, together with its corporate development
and licensing efforts, has yielded a portfolio of pharmaceutical products
including Aptiom^® (eslicarbazepine acetate), Latuda^® (lurasidone HCl)
tablets, Lunesta^® (eszopiclone) tablets, Xopenex^® (levalbuterol HCI)
inhalation solution, Xopenex HFA^® (levalbuterol tartrate) inhalation aerosol,
Brovana^® (arformoterol tartrate) inhalation solution, Omnaris^® (ciclesonide)
nasal spray, Zetonna^® (ciclesonide) nasal aerosol and Alvesco^® (ciclesonide)
Sunovion, an indirect, wholly-owned U.S. subsidiary of Dainippon Sumitomo
Pharma Co., Ltd., is headquartered in Marlborough, Mass. More information
about Sunovion Pharmaceuticals Inc. is available at www.sunovion.com.
About Dainippon Sumitomo Pharma Co., Ltd. (DSP)
DSP is a top-ten listed pharmaceutical company in Japan with a diverse
portfolio of pharmaceutical, animal health and food and specialty products.
DSP aims to produce innovative pharmaceutical products in the Psychiatry &
Neurology area and the Oncology area, which have been designated as the focus
therapeutic areas. DSP is based on the merger in 2005 between Dainippon
Pharmaceutical Co., Ltd., and Sumitomo Pharmaceuticals Co., Ltd. Today, DSP
has about 7,000 employees worldwide. Additional information about DSP is
available through its corporate website at www.ds-pharma.com.
LATUDA ^ is a registered trademark of Dainippon Sumitomo Pharma Co., Ltd.
LUNESTA, XOPENEX, XOPENEX HFA, and BROVANA are registered trademarks of
Sunovion Pharmaceuticals Inc. OMNARIS and ALVESCO are registered trademarks of
Takeda GmbH, used under license.
For a copy of this release, visit Sunovion’s web site at www.sunovion.com
©2013 Sunovion Pharmaceuticals Inc. All rights reserved.
^1 National Institutes of Health. “NINDS Epilepsy Information Page.” Accessed
5 September 2013. <http://www.ninds.nih.gov/disorders/epilepsy/epilepsy.htm>.
^2 Epilepsy Foundation. “Partial Seizures.” Accessed 5 September 2013.
^3 Dartmouth Medical School. “Disorders of the Central Nervous System: A
Primer (Chapter 22: Epilepsy).” Accessed 5 September 2013.
^4 IOM (Institute of Medicine). 2012. Epilepsy across the spectrum: Promoting
health and understanding. Washington, DC: The National Academies Press.
^5 Brodie MJ, Barry SJE, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment
response in newly diagnosed epilepsy. Neurology. 2012;78:1548-1554.
Sunovion Pharmaceuticals Inc.
Patricia Moriarty, 508-787-4279
Senior Director, Corporate Communications
Press spacebar to pause and continue. Press esc to stop.