Efficacy of USL255 Across Partial-Onset Seizure Types and Refractory Patient Status: Subgroup Analyses From the PREVAIL Study (P3.263)

OBJECTIVE: Assess the efficacy of USL255, once-daily extended-release topiramate, in patients subdivided by baseline seizure type and antiepileptic drug (AED) use. BACKGROUND: Seizure type, concomitant AED use, and the number of previous AEDs may influence responsiveness of a patient to AED treatment. These analyses attempt to identify effectiveness of USL255 in treatment-resistant patient subgroups. DESIGN/METHODS: In this double-blind, phase 3 study (PREVAIL; NCT01142193), patients with partial-onset seizures (POS) on 1-3 concomitant AEDs were randomized to placebo (n=125) or USL255 (n=124), titrated over 3 weeks (50 mg/week), and maintained at 200 mg/day for 8 weeks. Efficacy assessments included median percent reduction from baseline in weekly POS frequency and 50% responder rate. Subgroup analyses included efficacy by 1) POS seizure type, 2) concomitant AED use, 3) lifetime AED use, and 4) refractory status (‘highly refractory’, 蠅2concomitant AEDs and 蠅4 lifetime AEDs; ‘less refractory’, 1 concomitant AED or <4 lifetime AEDs), although PREVAIL was not powered for statistical analyses in these subgroups. RESULTS: In subjects experiencing disabling seizures (complex partial with/without secondary generalization), USL255 significantly reduced weekly seizure frequency (40.6% vs 17.7%; P P =.001) vs placebo. Both seizure reduction and responder rate were significantly improved in patients concurrently taking 蠅3 AEDs ( P P =.001 and .007, respectively). In patients deemed ‘highly refractory’, reduction in seizure frequency was 2-fold higher with USL255 vs placebo (40.4% vs 18.1%; P =.004) and responder rate was significantly improved (38.5% vs 19.0%; P =.023). CONCLUSIONS: USL255 was efficacious as an adjunctive treatment for POS, with a variety of concomitant AEDs, and in highly refractory patients. Results from the PREVAIL study demonstrate broad and consistent efficacy of USL255, which may provide a significant benefit to patients with epilepsy. Study Supported by: Upsher-Smith Laboratories, Inc. Disclosure: Dr. Blatt has received personal compensation for activities with Upsher-Smith and GlaxoSmithKline, Inc. Dr. Nagaraddi has received personal compensation for activities with Upsher-Smith Laboratories as a consultant, and with UCB Biosciences as a speaker. Dr. Nagaraddi has received research support from Upsher-Smith Laboratories and UCB Biosciences. Dr. Hogan has received research support from Eisai Inc., and Upsher Smith. Dr. Arnold has received personal compensation for activities with UCB Pharma, Upsher-Smith, and Eisai Inc. as a consultant. Dr. Lawson has received personal compensation for activities with Upsher-Smith Laboratories as a consultant. Dr. Lawson has received research support from Upsher-Smith Laboratories. Dr. Anders has received personal compensation for activities with Upsher-Smith Laboratories, Inc. Dr. Clark has received personal compensation for activities with Upsher-Smith Laboratories, Inc. Dr. Halvorsen has received personal compensation for activities with Upsher-Smith Laboratories, Inc. Dr. Halvorsen holds stock in Medtronic Inc., Stryker, Elan Corp., Teva Neuroscience, Gilead, Pfizer Inc., and Amgen Inc. Dr. Chung has received personal compensation for activities with UCB Pharma, Supermus, Esai Inc., Lundbeck Research USA, Inc., Upshire-Smith, and SK Life Science.