Dexpramipexole effects on functional decline and survival in subjects with amyotrophic lateral sclerosis in a Phase II study: Subgroup analysis of demographic and clinical characteristics

Abstract

Our objective was to explore treatment effects in patient subgroups using post hoc analyses of data from part 2 of the dexpramipexole Phase II study. Subjects with amyotrophic lateral sclerosis (ALS) received dexpramipexole 300 mg/day or 50 mg/day for 24 weeks. Treatment effects on the slope of the revised ALS Functional Rating Score (ALSFRS-R) and Combined Assessment of Function and Survival (CAFS) were evaluated in dichotomized subgroups: riluzole use, gender, site of symptom onset. Other subgroups were dichotomized using median baseline values for age, ALSFRS-R, slow vital capacity, symptom duration, diagnostic delay, and progression rate. Results showed that there was a 21% reduction in ALSFRS-R decline favoring the 300-mg vs. 50-mg arm (p = 0.177); mean CAFS ranking was significantly higher in the 300-mg vs. 50-mg arm (52.4 vs. 41.1; p = 0.046). Trends were recapitulated in virtually all subgroups. Generally, ALSFRS-R decline was reduced and CAFS rankings were higher in the 300-mg vs. 50-mg arm across subgroups. CAFS rankings were significantly higher in the 300-mg vs. 50-mg arm among subjects with ALSFRS-R scores ≤35, symptom duration <18.7 months, or progression rate ≥ 0.7 points/month (p < 0.03). In conclusion, the observed benefit of 300- vs. 50-mg dexpramipexole on functional decline and survival was generally consistent among subjects regardless of baseline characteristics.

Key words::

• Amyotrophic lateral sclerosis
• dexpramipexole
• ALSFRS-R
• CAFS
• Phase II

Disclosure of interest: S. A. Rudnicki has served as a consultant and study investigator for Knopp Biosciences LLC. J. D. Berry has served as a consultant for Biogen Idec and receives funding from the MDA and ALS Therapy Alliances. E. Ingersoll and D. Archibald are employees of Knopp Biosciences LLC. M. E. Cudkowicz served on an advisory board for Biogen Idec, is a DSMB member for Trophos and consultant for GSK and Shire; she was also the recipient of the 1996 AAN Clinical Research Training Fellowship. D. A. Kerr and Y. Dong are employees of Biogen Idec. The authors alone are responsible for the content and writing of the paper.

The Phase II study was sponsored and conducted by Knopp Biosciences LLC. This report was sponsored by Biogen Idec. Medical writing assistance funded by Biogen Idec was provided by Linda Goldstein of UBC Scientific Solutions.