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Ortho-McNeil Neurologics, Inc. Phase III Data Demonstrate Efficacy and Tolerability of Carisbamate as an Adjunctive Therapy for Partial Onset Seizures



12/8/2008 6:47:06 AM

SEATTLE, Dec. 6 /PRNewswire/ -- Phase III data on carisbamate, an investigational compound recently filed with the FDA for the adjunctive treatment of partial onset seizures (POS) in patients 16 years of age and older, was presented today during the poster sessions of the 32nd Annual Meeting of the American Epilepsy Society.

Results from two identical placebo-controlled clinical trials investigating the efficacy, safety and tolerability of carisbamate as an adjunctive treatment for patients with POS were presented along with results of a pharmacokinetic/ pharmacodynamic (PK/PD) analysis.

"Although several new antiepileptic drugs have become available in the past decade, there is still unmet patient need. Long-term treatment success is not only determined by seizure control, but equally by tolerability, which is reflected by a patient's ability to remain on medication," said Michael Sperling, M.D. of Thomas Jefferson University and an investigator in the trials. "The carisbamate data presented at AES not only demonstrate benefit of carisbamate in reducing seizure frequency in some patients with partial onset seizures, but also shows an impressive tolerability profile."

Adjunctive Therapy of Partial Onset Seizures in Adults

Two identically designed, randomized, double blind, placebo-controlled global studies were presented in the first poster. Patients with an established diagnosis of uncontrolled POS for one year or more were eligible. The subjects remained on stable doses of a prescribed antiepileptic drug (AED) for 8-weeks (baseline phase) and were then randomized to receive carisbamate 200 mg/day, carisbamate 400 mg/day, or placebo on top of these existing AEDs. Efficacy endpoints were median percent reduction in seizure frequency in the double blind phase compared to the baseline phase, and the proportion of patients with 50% or greater reduction in POS frequency during the 12-week double blind phase.

Carisbamate was well tolerated, with minimal central nervous system-related adverse events and a low discontinuation rate. The most common adverse events were dizziness and somnolence. The rate of treatment-emergent adverse events resulting in discontinuation from carisbamate was 3% in each study. Results showed that treatment with carisbamate 400 mg resulted in significant improvement in both efficacy measures compared with placebo in study 1, but not in study 2. Carisbamate 200 mg/day did not differ from placebo in either study. In both studies, concomitant use of enzyme-inducing AEDs lowered plasma levels of carisbamate by up to 44% (40% in study 1 and 44% in study 2). As a result, there were greater percentage reductions in POS frequency among patients treated with carisbamate who received concomitant non-enzyme inducing AEDs.

PK/PD Modeling of the Effect of Carisbamate

A second poster showed results of an analysis of three studies, which evaluated the efficacy of carisbamate, using a PK/PD model to predict the effect of carisbamate over a dose range of 400 mg/day to 1200 mg/day. The relationship between percent reduction of POS from baseline and steady state trough concentration was investigated.

The model showed that seizure reduction increased with greater drug exposure levels. Carisbamate pharmacokinetics were influenced by the co-administration of enzyme-inducing AEDs, which reduced carisbamate exposure by about 33-40%. In all three studies separately, a statistically significant positive relationship between seizure rate reduction and steady state trough concentrations was found. The PK/PD simulations predicted that treatment with 400 mg/day provides clinically meaningful effects for all subjects, with further increase in effect with dosages of 800 mg and 1200 mg/day for patients on enzyme-inducing or non-enzyme inducing AEDs.

The data presented at AES are among the data supporting the New Drug Application (NDA) filed for carisbamate by J&JPRD in October 2008. If approved by the FDA, carisbamate will be marketed by Ortho-McNeil Neurologics, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Carisbamate has received provisional approval by the FDA to be marketed under the brand name of COMFYDE(TM).

About Partial Onset Seizures and Epilepsy

Epilepsy is one of the most common disorders of the nervous system, defined by recurrent unprovoked seizures. It is categorized as "primary generalized" or "partial onset" depending on the specific location of the abnormal electrical activity in the brain that characterizes the disorder. Partial-onset seizures are common and may often be difficult to treat. Partial-onset seizures are most often characterized by simple or complex repetitive movements, but virtually any sensory or emotional symptom can also occur as part of a partial seizure, including complex visual or auditory hallucinations. There are two categories of partial onset seizures: simple partial seizures (in which consciousness is retained), and complex partial seizures (in which consciousness is impaired or lost). Partial seizures can generalize and lead to tonic clonic seizures, during which the patient loses consciousness and is at risk for falling or injury.

About J&JPRD

Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) is a subsidiary of Johnson & Johnson, the world's most broadly-based producer of health care products. J&JPRD is headquartered in Raritan, N.J., and has facilities throughout Europe, the United States and Asia. J&JPRD is leveraging drug discovery and drug development in a variety of therapeutic areas, including CNS, Internal Medicine and Oncology, to address unmet medical needs worldwide. More information can be found at http://www.jnjpharmarnd.com.

About Ortho-McNeil Neurologics

Headquartered in Titusville, NJ, Ortho-McNeil Neurologics, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., a subsidiary of Johnson & Johnson, focuses exclusively on providing solutions that improve neurological health. The company currently markets products for Alzheimer's disease, epilepsy and acute and preventive migraine treatment. In conjunction with internal and external research partners, Ortho-McNeil Neurologics continues to explore new opportunities to develop solutions for unmet health care needs in neurology.

Note Regarding Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the J&JPRD's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 30, 2007. Copies of this Form 10-K, as well as subsequent filings, are available online at http://www.sec.gov, http://www.jnj.com or on request from Johnson & Johnson. J&JPRD does not undertake to update any forward-looking statements as a result of new information or future events or developments.

Contacts: Media Kara Russell: (609) 730-3592 KRussel3@its.jnj.com

Investor Relations Louise Mehrotra: (732) 524-6491 Lesley Fishman: (732) 524-3922

Source: Ortho-McNeil Neurologics


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