Dexpramipexole Effects on Functional Decline in ALS Patients in a Phase II Study: Subgroup Analysis of Demographic and Clinical Characteristics (P04.149)

Abstract

Objective: We conducted post hoc analyses of data from a two-part, Phase II study of oral dexpramipexole to explore potential differential treatment effects in a variety of patient subgroups. Background In the study, dexpramipexole was well tolerated for up to 9 months and showed dose-dependent trends in abating functional decline and improving survival in ALS patients. Design/Methods: Post-hoc analyses were performed on data from Part 2 of the study. After a study drug washout, ALS patients (n=92) were randomized to high- (300 mg) or low-dose (50 mg) dexpramipexole for 24 weeks. We evaluated the effects of dexpramipexole on the slope of the revised ALS Functional Rating Score (ALSFRS-R) in various patient subgroups. Subgroup variables included: riluzole use vs no riluzole use, gender, and site of symptom onset (bulbar vs limb). Other subgroups were formed using continuous variables dichotomized on mean baseline values: age ( Results: Overall, there was a 21% reduction in the ALSFRS-R decline favoring the 300-mg vs 50-mg dexpramipexole group (p=0.177). This statistical trend was recapitulated in all subgroups analyzed. For example, patients taking riluzole who received 300-mg vs 50-mg dexpramipexole showed reduced ALSFRS-R declines (−1.08 vs −1.30) as did men taking 300-mg vs 50-mg dexpramipexole (−1.08 vs −1.22). Likewise, patients with a baseline ALSFRS-R Conclusions: These results suggest that the slightly larger benefit of 300-mg vs 50-mg dexpramipexole on functional decline is uniform across a diverse study population regardless of baseline demographic and clinical characteristics. Supported by: Sponsored by Biogen Idec. Medical writing assistance, funded by Biogen Idec, was provided by Linda Goldstein at UBC Scientific Solutions. Disclosure: Dr. Rudnicki has received research support from Biogen Idec. Dr. Berry has nothing to disclose. Dr. Ingersoll has received personal compensation for activities with Knopp Biosciences LLC as an employee. Dr. Ingersoll holds stock and/or stock options in Knopp Biosciences LLC, which sponsored research in which Dr. Ingersoll was involved as an investigator. Dr. Archibald has received personal compensation for activities with Knopp Biosciences LLC as an employee. Dr. Archibald holds stock and/stock options in Knopp Biosciences LLC, which sponsored research in which Dr. Archibald was involved as an investigator. Dr. Cudkowicz has received personal compensation for activities with Synapse, Trophos, and Acclerson as a data safety monitoring board chair or an advisory board member. Dr. Kerr has received personal compensation for activities with Teva Neuroscience, Biogen Idec, and Pfizer Inc as a speaker. Dr. Kerr has received compensation for serving as a co-founder of Nerveda Inc. Dr. Kerr has received research support from Nerveda Inc. Dr. Dong has received personal compensation for activities with Biogen Idec as an employee.