Phase III Data Demonstrate Efficacy and Tolerability of Carisbamate as an Adjunctive Therapy for Partial Onset Seizures

Sunday, December 7, 2008 General News
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SEATTLE, Dec. 6 Phase III data on carisbamate, aninvestigational compound recently filed with the FDA for the adjunctivetreatment of partial onset seizures (POS) in patients 16 years of age andolder, was presented today during the poster sessions of the 32nd AnnualMeeting of the American Epilepsy Society.

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

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

Adjunctive Therapy of Partial Onset Seizures in Adults

Two identically designed, randomized, double blind, placebo-controlledglobal studies were presented in the first poster. Patients with anestablished 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 carisbamate200 mg/day, carisbamate 400 mg/day, or placebo on top of these existing AEDs.Efficacy endpoints were median percent reduction in seizure frequency in thedouble blind phase compared to the baseline phase, and the proportion ofpatients with 50% or greater reduction in POS frequency during the 12-weekdouble blind phase.

Carisbamate was well tolerated, with minimal central nervoussystem-related adverse events and a low discontinuation rate. The most commonadverse events were dizziness and somnolence. The rate of treatment-emergentadverse events resulting in discontinuation from carisbamate was 3% in eachstudy. Results showed that treatment with carisbamate 400 mg resulted insignificant improvement in both efficacy measures compared with placebo instudy 1, but not in study 2. Carisbamate 200 mg/day did not differ fromplacebo in either study. In both studies, concomitant use of enzyme-inducingAEDs 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 POSfrequency among patients treated with carisbamate who received concomitantnon-enzyme inducing AEDs.

PK/PD Modeling of the Effect of Carisbamate

A second poster showed results of an analysis of three studies, whichevaluated the efficacy of carisbamate, using a PK/PD model to predict theeffect of carisbamate over a dose range of 400 mg/day to 1200 mg/day. Therelationship between percent reduction of POS from baseline and steady statetrough concentration was investigated.

The model showed that seizure reduction increased with greater drugexposure levels. Carisbamate pharmacokinetics were influenced by theco-administration of enzyme-inducing AEDs, which reduced carisbamate exposureby about 33-40%. In all three studies separately, a statistically significantpositive relationship between seizure rate reduction and steady state troughconcentrations was found. The PK/PD simulations predicted that treatment with400 mg/day provides clinically meaningful effects for all subjects, withfurther increase in effect with dosages of 800 mg and 1200 mg/day for patientson enzyme-inducing or non-enzyme inducing AEDs.

The data presented at AES are among the data supporting the New DrugApplication (NDA) filed for carisbamate by J&JPRD in October 2008. If approvedby the FDA, carisbamate will be marketed by Ortho-McNeil Neurologics, adivision of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Carisbamate hasreceived provisional approval by the FDA to be marketed under the brand nameof 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 "primarygeneralized" or "partial onset" depending on the specific location of theabnormal 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 complexrepetitive movements, but virtually any sensory or emotional symptom can alsooccur as part of a partial seizure, including complex visual or auditoryhallucinations. There are two categories of partial onset seizures: simplepartial seizures (in which consciousness is retained), and complex partialseizures (in which consciousness is impaired or lost). Partial seizures cangeneralize and lead to tonic clonic seizures, during which the patient losesconsciousness 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 producerof health care products. J&JPRD is headquartered in Raritan, N.J., and hasfacilities throughout Europe, the United States and Asia. J&JPRD isleveraging drug discovery and drug development in a variety of therapeuticareas, including CNS, Internal Medicine and Oncology, to address unmet medicalneeds worldwide. More information can be found at

About Ortho-McNeil Neurologics

Headquartered in Titusville, NJ, Ortho-McNeil Neurologics, Division ofOrtho-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 andacute and preventive migraine treatment. In conjunction with internal andexternal research partners, Ortho-McNeil Neurologics continues to explore newopportunities 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 thePrivate Securities Litigation Reform Act of 1995. These statements are basedon current expectations of future events. If underlying assumptions proveinaccurate or unknown risks or uncertainties materialize, actual results couldvary materially from the J&JPRD's expectations and projections. Risks anduncertainties include general industry conditions and competition; economicconditions, such as interest rate and currency exchange rate fluctuations;technological advances and patents attained by competitors; challengesinherent in new product development, including obtaining regulatory approvals;domestic and foreign health care reforms and governmental laws andregulations; and trends toward health care cost containment. A further listand description of these risks, uncertainties and other factors can be foundin Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscalyear ended December 30, 2007. Copies of this Form 10-K, as well as subsequentfilings, are available online at, or onrequest from Johnson & Johnson. J&JPRD does not undertake to update anyforward-looking statements as a result of new information or future events ordevelopments.Contacts: Media Kara Russell: (609) 730-3592 Investor Relations Louise Mehrotra: (732) 524-6491 Lesley Fishman: (732) 524-3922

SOURCE Ortho-McNeil Neurologics

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