Biopharmaceuticals Neurology

 News Release - December 4, 2006

Phase II Data Shows Ovation's Novel Compound Clobazam to Be Well Tolerated in Patients With Catastrophic Epilepsy

Data Presented at the North American Regional Epilepsy Congress Demonstrate Statistically Significant Reduction in Drop Seizures

SAN DIEGO, Dec. 4 (HSMN NewsFeed) -- Results from the first study in the United States designed to evaluate the safety and efficacy of clobazam as adjunctive therapy in patients with Lennox-Gastaut syndrome (LGS), one of the most severe forms of childhood epilepsy, demonstrated that clobazam is well tolerated. In the trial, clobazam was shown to be effective in significantly reducing drop (or atonic) seizures, the most debilitating of the LGS seizure types, which can result in severe trauma to the brain and body, by 85.3 percent compared to baseline (in the high dose group versus 12 percent in the low dose group; P=.0001). Adverse events leading to the discontinuation of clobazam were rare. Data were presented today at the North American Regional Epilepsy Congress.

"LGS is a devastating form of epilepsy typically treated with potent anti-convulsants that often cause serious adverse events," said Joan A. Conry, M.D., Professor of Neurology and Pediatrics in the Department of Neurology at Children's National Medical Center in Washington, D.C., and a principal investigator in the study. "The prognosis for LGS sufferers is poor so finding effective, less toxic, treatments is essential. These findings are significant because they show the potential of clobazam to reduce the catastrophic impact of LGS for patients in the U.S."

This phase II, multi-center, randomized, double-blind, dose-finding clinical trial was the first study conducted in the U.S. to evaluate the safety and efficacy of clobazam as adjuvant therapy in patients with LGS. Sixty-eight patients (ages 2 to 26 years) with LGS were randomized to two treatment groups with a low dose (target of 0.25 mg/kg/day) of clobazam or a high dose (target of 1.0 mg/kg/day) for a total treatment duration of up to 10 weeks.

Results demonstrated that in the high dose clobazam group more than 83 percent of LGS patients experienced 50 percent or greater reduction in weekly drop seizures from baseline (P=.0001) and 67 percent experienced a reduction of 75 percent or greater (P=.0006). Nearly 15 percent of patients experienced complete elimination (100 percent reduction) of drop seizures during the course of the study though it did not attain statistical significance (P=.0629).

The majority of adverse events (AEs) observed during the study were mild or moderate in severity. In total, 85 percent of patients reported an AE, with 46 percent mild, 35 percent moderate, and 4 percent severe. No serious adverse events resulted in premature discontinuation of clobazam.

After the study's maintenance period, patients either continued in the open-label extension study or were tapered off clobazam for up to three weeks. Of the 68 patients in the study, nearly all (n=61) elected to continue therapy during the open label evaluation and currently remain on treatment with clobazam. The duration on drug to date for the earliest patient dosed continues at 13 months.

"These findings validate what we have seen with clobazam research around the world and reinforces our commitment to develop this new therapy in the U.S. for people with LGS," said Stephen D. Collins M.D., Ph.D., Chief Scientific Officer and Vice President of Clinical Affairs, OVATION Pharmaceuticals. "Clobazam is one of a number of important CNS products coming through our development pipeline. It follows vigabatrin, another novel epilepsy treatment being evaluated for refractory complex partial seizures and infantile spasms. We are both excited and encouraged by these latest data, which shows promise in our ability to help people with such a difficult to treat catastrophic disease."

About Lennox-Gastaut syndrome

Lennox-Gastaut syndrome is a rare but debilitating form of epilepsy that frequently persists into adulthood(1). This form of catastrophic epilepsy, characterized by several seizure types, represents up to 10 percent of all childhood epilepsies(2) and onset typically occurs between three and 10 years of age. Drop attacks (atonic seizures) are frequent in LGS and responsible for most injuries associated with falls. Up to 90 percent of children with LGS are affected by mental retardation and these children commonly experience behavioral and sleep disturbances as well(3).

"The impact of epilepsy, particularly LGS, on a patient and family's life can be both devastating and overwhelming," said Phil Gattone, M.Ed., Board Member and former chief executive officer, Epilepsy Foundation of Greater Chicago Executive Committee. "Without a cure, we can only hope for new therapies that improve seizure control, especially for drop seizures that can cause great harm, and do so with minimal side effects. We are particularly excited about a product like clobazam."

About Clobazam

As a 1,5-benzodiazepine, clobazam has a distinctive chemical structure with associated unique properties when compared with other currently available benzodiazepines. It was initially developed to decrease the adverse effects seen with 1,4-benzodiazepines while still maintaining efficacy. Clobazam in animal models works both by intensifying gamma-aminobutyric acid (GABA)-mediated inhibitory effects and by increasing activity of glutamate transporters.

Currently, clobazam is widely available worldwide with approvals in more than 100 countries for various uses in both children and adults, including the treatment of epilepsy and anxiety. Though not currently approved for use in the U.S., OVATION Pharmaceuticals has undertaken a clinical development program to gain Food and Drug Administration approval for clobazam for the treatment of pediatric and adult patients with refractory epilepsy, specifically in LGS.

About OVATION Pharmaceuticals

OVATION is a fast growing biopharmaceutical company that develops, manufactures and markets medically necessary therapies to satisfy unmet medical needs for patients with severe illnesses. Headquartered in Deerfield, Ill., with products available in more than 85 countries, OVATION is committed to having a significant impact on patients' lives through its focus on central nervous system (CNS), hematology/oncology, and hospital-based therapies. The four new product launches the company expects over the next five years will be fueled by its late-stage CNS pipeline, which is one of the most robust in the industry. OVATION has been recognized for excellence in the global pharmaceutical and biotechnology industries with the 2006 "Pharma Company of the Year" award from Scrip magazine for small to mid-sized enterprises. More information about the company, its products and full prescribing information may be found at http://www.ovationpharma.com .

(1) Beaumanoir A, Blume, W. The Lennox-Gastaut syndrome- Symptomatology During the Seizure Disorder. In: J. Roger MB, C. Dravet, P. Genton, C.A. Tassinari, & P. Wolf, ed. Epileptic Syndromes in Infancy, Childhood, and Adolescence 3rd ed. London: John Libbey & Co., Ltd. 2002:113-135.

(2) Markand ON. Lennox-Gastaut syndrome (childhood epileptic encephalopathy). J Clin Neurophysiol. 2003;20:426-441.

(3) Crumrine PK. Lennox-Gastaut syndrome. J Child Neurol. 2002;17 Suppl 1:S70-75.

Source: OVATION Pharmaceuticals

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