Abstracts

SPM 927 (formerly harkoseride) is being developed by Schwarz Biosciences as an oral and intravenous formulation for the treatment of partial seizures and neuropathic pain. An ongoing Phase 2 extension trial (SP615) is assessing the safety and efficacy of SPM 927 following long-term exposure. Subjects with refractory epilepsy who complete primary trials of SPM 927 as adjunctive therapy are included. The aim of this evaluation is to describe the safety and efficacy profile of SPM 927 following 24 weeks in the extension trial. The subjects in the evaluation completed open-label primary trials (SP598 and SP607) before enrolling.
The primary trials enrolled subjects who had uncontrolled partial seizures with or without secondary generalization ([ge] 4 seizures/ 28 days) and had been taking a stable regimen of up to two antiepileptic drugs (AEDs) with or without concurrent vagus nerve stimulation. Subjects were titrated to their maximum tolerated dose. Subsequently, subjects enrolled in the extension, where investigators could increase or decrease the dose of SPM 927 (100 to 600 mg/day) and concomitant AEDs at their discretion. Clinic visits were conducted at Weeks 4, 8, 16, and 24. Efficacy was evaluated by the percent change in seizure frequency from baseline of the primary trial to endpoint (8-week period from Weeks 16 to 24) and the 50% responder rate (percent of subjects with [ge]50% reduction in seizure frequency compared with baseline of the primary trial) at endpoint. Maintenance was assessed by the responder rate at endpoint for subjects who were responders in the maintenance phase of the primary trials.
A total of 68 subjects enrolled in the extension and are included in this analysis. Mean age at entry was 40.2 years. Median years since being diagnosed with epilepsy was 25.1 years.
Of 68 subjects enrolled, 54 had data available at Week 24. Ten subjects discontinued prior to reaching Week 24, 8 for lack of efficacy, 1 for noncompliance, and 1 for an adverse event (dry mucous membranes). The median dose was 400 mg/day SPM 927. For subjects who stayed in the trial for 24 weeks, median dose was 475 mg/day. Adverse events reported were most frequently CNS-related and mild or moderate in severity.
The median percent reduction in seizure frequency for subjects with data available through Week 24 was 53% (44% by LOCF analysis). Of these subjects, 54% were 50% responders at endpoint. Of the subjects who were 50% responders at completion of the primary trial, 75% were responders at endpoint. Two of these subjects were seizure-free throughout the first 24 weeks.
During the first 24 weeks of an ongoing extension trial, SPM 927 has been well tolerated as adjunctive therapy with 1 of 68 subjects discontinuing due to an adverse event. SPM 927 has shown seizure reductions as adjunctive therapy for partial seizures.
[Supported by: Schwarz Biosciences Inc. WR and GM received research grants. GM received consulting fees.]