New Data Show Efficacy and Safety of Eslicarbazepine Acetate in the Treatment of Epilepsy

Update: Aptiom (eslicarbazepine acetate) Now FDA Approved - November 8, 2013

MARLBOROUGH, Mass.--(BUSINESS WIRE)--Sep 24, 2008 - Sepracor Inc. (Nasdaq: SEPR) announced that positive data from three Phase III studies presented today at the 8th European Congress of Epileptology in Berlin, demonstrated that eslicarbazepine acetate, a novel once-daily anti-epileptic agent, significantly reduced the frequency of partial seizures in patients with refractory partial epilepsy, in combination with other anti-epileptic agents.(1), (2), (3)

In addition, treatment with eslicarbazepine acetate significantly improved patient quality of life, reduced depressive symptoms and demonstrated sustained reduction in partial seizure frequency during a one-year, open-label period.(4), (5), (6)

"When assessing the potential of anti-epileptic agents, it is as important to consider the implications on the quality of a patient's day-to-day life, as well as effective seizure control," said Professor E. Ben-Menachem, University of Goteborg, Sweden and lead clinical investigator for eslicarbazepine acetate. "In addition to sustained reductions in seizure frequency, eslicarbazepine acetate demonstrated a significant improvement in patient quality of life and reduction in depressive symptoms."

"These data suggest that eslicarbazepine acetate has the potential to become an important treatment option for patients in North America whose seizures are not adequately controlled with existing anti-epileptic agents," said Mark H.N. Corrigan, M.D., Executive Vice President, Research and Development at Sepracor. "In addition, we plan to conduct monotherapy and pediatric studies with the goal of broadening eslicarbazepine acetate's potential use."

Epilepsy is one of the most common neurological diseases and, according to the Epilepsy Foundation, an estimated 2.7 million people in the U.S. have epilepsy. Treatment of partial seizures, the most common type of epilepsy, presents a constant challenge with over half of patients not achieving adequate seizure control with current anti-epileptic drugs.(7)

Eslicarbazepine acetate, a new anti-epileptic drug candidate that selectively inhibits the rapid-firing nerve cells that cause seizures, has been developed to address the need for a new anti-epileptic agent that offers a reduction in seizure frequency combined with an acceptable tolerability profile. Eslicarbazepine acetate is currently under review by the EMEA (European Medicines Agency) for the treatment of partial-onset seizures with or without secondary generalization in combination with other anti-epileptic drugs. An NDA submission to the U.S. Food and Drug Administration is targeted for the end of 2008 or early 2009.

About the trials

The three Phase III, multi-center, randomized, double-blinded, placebo-controlled trials involved more than 1,000 patients from 23 countries. Patients had a history of at least four partial seizures per month despite treatment with up to three concomitant anti-epileptic drugs.(1), (2), (3)

During the trials, patients were randomized to eslicarbazepine acetate or placebo and after a 2-week titration period, were assessed over a 12-week maintenance period, with continued follow-up over a one- year, open-label period.(1), (2), (3), (6)

Efficacy

Over the 12-week maintenance period, eslicarbazepine acetate 800 mg and 1200 mg reduced seizure frequency by over one-third, and was significantly more effective than placebo. This significant decrease in seizure frequency was sustained over the one-year, open-label treatment period and was consistent regardless of baseline therapy.(1), (2), (3) Similar positive findings were observed in the responder rate (> or = 50% decrease in seizure frequency) for eslicarbazepine acetate 800 mg and 1200 mg that ranged between 32 percent and 43 percent across all three Phase III trials.(1), (2), (3)

Tolerability

In these studies, the safety profile of eslicarbazepine acetate was favorable. The majority of treatment-related adverse events were mild or moderate in severity and after six weeks, no relevant differences in the incidence of adverse events were apparent between patients treated with eslicarbazepine acetate and patients treated with placebo. In patients treated with eslicarbazepine acetate, the incidence of central nervous system side effects was low.(1), (2), (3)

Quality of life and depressive symptoms

The effect of eslicarbazepine acetate on quality of life was analyzed using the Quality of Life Epilepsy Inventory-31 (QOLIE-31) scale. There was a statistically and clinically significant improvement from baseline during long-term, open-label therapy, including:(4)

-- 16 percent mean relative improvement in overall quality of life (p<0.0001);

-- 51 percent improvement in worry about seizures (p<0.0001); and

-- 41 percent improvement in social function (p<0.001).

Improvement in depressive symptoms was also measured using the Montgomery Asberg Depression Rating Scale (MADRS). Eslicarbazepine acetate demonstrated a significant improvement in depressive mood and symptoms from baseline (p<0.0001).(5)

About partial seizures and their treatment

Epilepsy is one of the most common neurological diseases and, according to the Epilepsy Foundation, an estimated 2.7 million people in the U.S. have epilepsy. Treatment of partial seizures, the most common type of epilepsy, presents a constant challenge - up to 58 percent of patients with partial seizures do not achieve seizure control with current anti-epileptic drugs.(7)

Furthermore, adverse events, such as dizziness and somnolence, are highly prevalent with existing anti-epileptic agents and may affect as many as 97 percent of patients.(8) Hence, there is a need for new anti-epileptic agents that offer effective reduction in seizure frequency combined with a favorable safety profile.

Epilepsy is characterized by abnormal firing of impulses from nerve cells in the brain. In partial-onset epilepsy, these bursts of electrical activity are initially focused in specific areas of the brain, but may become more generalized; the symptoms vary according to the affected areas. Nerve impulses are triggered via voltage-gated sodium channels in the nerve cell membrane.

About Eslicarbazepine Acetate

Eslicarbazepine acetate is a novel voltage-gated sodium channel blocker that has been studied to reduce the frequency of partial-onset seizures when used in combination with other anti-epileptic drugs. This treatment has the potential to be a new therapeutic option for patients who continue to suffer partial seizures despite receiving treatment with other anti-epileptic agents, with the potential for additional benefits in terms of improvements in quality of life and depressive symptoms.(1), (2), (3), (4), (5), (6)A Marketing Authorization Application for eslicarbazepine acetate was submitted to the EMEA in March 2008 by its innovator, Bial - Portela & Ca, S.A., a privately held Portuguese pharmaceutical company. Eslicarbazepine acetate, which Bial plans to market in the European Union under the name ZEBINIX(TM), is under review for the treatment of partial-onset seizures with or without secondary generalization, in combination with other anti-epileptic drugs. Sepracor acquired the rights to commercialize eslicarbazepine acetate for the U.S. and Canadian markets.

References

1. Elger C, Halasz P, Maia J et al. Efficacy and safety of eslicarbazepine acetate as add-on treatment in adults with refractory partial-onset seizures: BIA-2093-301 Study. Abstract and oral communication, presented at the 8th European Congress on Epileptology, Berlin, Germany, 21-25 September 2008.

2. Hufnagel A, Ben-Menachem E, Gabbai A et al. Efficacy and safety of eslicarbazepine acetate as add-on treatment in adults with refractory partial-onset seizures: BIA-2093-302 Study. Abstract and oral communication, presented at the 8th European Congress on Epileptology, Berlin, Germany, 21-25 September 2008.

3. Lopes-Lima J, Gil-Nagel A, Maia J et al. Efficacy and safety of eslicarbazepine acetate as add-on treatment in adults with refractory partial-onset seizures: BIA-2093-303 Study. Abstract and oral communication, presented at the 8th European Congress on Epileptology, Berlin, Germany, 21-25 September 2008.

4. Cramer J, Maia J, Almeida L, Soares-da-Silva P. Quality-of-life improvement during long-term treatment with eslicarbazepine acetate. Abstract and poster, presented at the 8th European Congress on Epileptology, Berlin, Germany, 21-25 September 2008.

5. Hodoba D, Czlonkowska A, Cramer J. Depressive symptoms improvement during long-term treatment with eslicarbazepine acetate. Abstract and poster, presented at the 8th European Congress on Epileptology, Berlin, Germany, 21-25 September 2008.

6. Guekht A, Elger C, Halasz P et al. Long-term treatment of partial epilepsy with eslicarbazepine acetate: results of a 1-year open-label extension study. Abstract and oral communication, presented at the 8th European Congress on Epileptology, Berlin, Germany, 21-25 September 2008.

7. Brodie MJ. Management strategies for refractory localization-related seizures. Epilepsia 2001;42(Suppl 3):27-30

8. Mei PA, Montenegro MA, Guerreiro MM, Guerreiro CA. Pharmacovigilance in epileptic patients using antiepileptic drugs. Arq Neuropsiquiatr 2006 Jun;64(2A): 198-201. Epub 2006 Jun 9

About Sepracor

Sepracor Inc. is a research-based pharmaceutical company dedicated to treating and preventing human disease by discovering, developing and commercializing innovative pharmaceutical products that are directed toward serving large and growing markets and unmet medical needs. Sepracor's drug development program has yielded a portfolio of pharmaceutical products and candidates with a focus on respiratory and central nervous system disorders. Currently marketed products include LUNESTA(R) brand eszopiclone, XOPENEX(R) brand levalbuterol HCl Inhalation Solution, XOPENEX HFA(R) brand levalbuterol tartrate Inhalation Aerosol, BROVANA(R) brand arformoterol tartrate Inhalation Solution, OMNARIS(TM) brand ciclesonide Nasal Spray and ALVESCO(R) brand ciclesonide HFA Inhalation Aerosol. Sepracor's corporate headquarters are located in Marlborough, Massachusetts.

Forward-Looking Statement

This news release contains forward-looking statements that involve risks and uncertainties, including statements with respect to the safety, efficacy and potential benefits of eslicarbazepine acetate, the possible submission of an NDA for eslicarbazepine acetate in late 2008 or early 2009, eslicarbazepine acetate potentially becoming an important treatment option for patients in North America whose seizures are not adequately controlled with existing anti-epileptic agents, Sepracor's plan to conduct monotherapy and pediatric studies with the goal of broadening eslicarbazepine acetate's potential use, and eslicarbazepine acetate's potential for additional benefits in terms of improvements in quality of life and depressive symptoms. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: clinical benefits, efficacy and safety of eslicarbazepine acetate; the timing and success of submission, acceptance, and approval of regulatory filings for eslicarbazepine acetate; unexpected delays in commercial introduction of, and the commercial success of, eslicarbazepine acetate; the success of Sepracor's alliance with Bial; the scope of Bial's and/or Sepracor's patents and the patents of others; the ability of Sepracor and Bial to attract and retain qualified personnel; and certain other factors that may affect future operating results that are detailed in Sepracor's quarterly report on Form 10-Q for the quarter ended June 30, 2008 filed with the Securities and Exchange Commission.

In addition, the statements in this press release represent Sepracor's expectations and beliefs as of the date of this press release. Sepracor anticipates that subsequent events and developments may cause these expectations and beliefs to change. However, while Sepracor may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Sepracor's expectations or beliefs as of any date subsequent to the date of this press release.

Zebinix is a trademark of Bial - Portela & Ca, S.A. Lunesta, Xopenex, Xopenex HFA and Brovana are registered trademarks of Sepracor Inc. Omnaris is a trademark and Alvesco is a registered trademark of Nycomed GmbH. For a copy of this release or any recent release, visit Sepracor's web site at www.sepracor.com.

Contact

Sepracor Inc.
Jonaé R. Barnes, 508-481-6700
Sr. Vice President, Investor Relations &
Corporate Communications

 

Posted: September 2008

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