The phase II multi-center, randomized, double-blind dose-finding study performed in the United States involved 68 patients (2 to 26 years of age) with LGS. Patients 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.
Data from the phase II clobazam clinical trial showed both clinically relevant and statistically significant results. There was a significant difference between the treatment groups in the percent reduction in weekly drop seizures from baseline to maintenance period (p-value=0.0001). Atonic or drop seizures are the most debilitating of the LGS seizure types and can result in severe trauma to the brain and limbs.
The data from the study show the mean percent reduction in weekly drop seizures from baseline for the high dose group was 85.3 percent and the reduction for the low dose group was 12 percent. More than 83 percent of patients from the high dose group have 50 percent or greater reduction in weekly drop seizures rate from baseline.
"These data support worldwide clinical experience with this agent - as well as findings from more than 20 previous studies - suggesting that clobazam has the potential to play a significant role in the treatment of patients with Lennox-Gastaut syndrome in the United States," said Joan 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. "We look forward to the results from further clinical trials confirming these findings." Clobazam is approved and widely used in other countries for various uses in both children and adults, including the treatment of epilepsy and anxiety, but has yet to be approved in the United States.
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, occurs in 3 to 10 percent of all childhood epilepsies(2) and onset typically occurs between 3 and 10 years of age. Seventy-five 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 data from this first U.S. trial with clobazam are highly encouraging, revealing the tremendous potential for this therapy in this country for people suffering from Lennox-Gastaut syndrome," said Jeffrey S. Aronin, President and Chief Executive Officer of OVATION. "This trial demonstrates continued progress in our development program designed to bring innovative medicines to critically ill patients with high unmet medical needs. This study is another important milestone in our development programs. It brings us one step closer to our goal of launching five new drugs over the next five years, as did the successful launch of our first U.S. FDA-approved product earlier this year."
Data from the phase II study will be presented at the American Epilepsy Society meeting in December.
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.
(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.
Contact: OVATION Pharmaceuticals, Inc. Sally Benjamin Young, 847-282-5770
Source: OVATION Pharmaceuticals, Inc.
