Effect of MD1003 (high dose Pharmaceutical grade Biotin) in the Treatment of Progressive MS: Earlier Treatment Results in Lower Disability Over 48 Months (P3.2-063)

Objective: To evaluate the effects of MD1003 during the open-label extension phase of the MS-SPI study.

Background: MS-SPI was a 12-month (M) double-blind study of MD1003 (n=103) vs placebo (n=51) in patients (pts) with nonactive progressive multiple sclerosis (PMS). As reported previously, expanded disability status scale (EDSS) and/or timed 25-foot walk improvement, mean EDSS (mEDSS) score, and clinical/subject global impression (CGI/SGI) score were all significantly (P<0.05) in favor of MD1003 vs placebo (Tourbah et al., 2016). In the open-label extension phase, all pts received MD1003. Here, we present data at 48M of follow-up (shown as MD1003>MD1003 [MM] vs placebo>MD1003 [PM]).

Design/Methods: A total of 133 pts (MM: 91; PM: 42) entered the extension phase. We assessed time to first decreased/increased EDSS (Kaplan-Meier), mEDSS change from baseline, and CGI/SGI.

Results: In time to first decreased/increased EDSS analyses up to 12M, the results favored MD1003 over placebo (hazard ratio [HR], 3.55 and 0.42, respectively), though they were not significant (P>0.05) in this relatively small study. In similar analyses up to 48M, the probability of improvement/worsening again favored MD1003 over placebo (HR, 2.47, P>0.05 and 0.80, P>0.05, respectively). Throughout the extension phase, the mean change in EDSS score was numerically lower in the MM group (vs PM group); the difference in mEDSS score between the MM and PM groups was significant at M18 (P<0.05) and M30 (P<0.05) but not at other timepoints. In the extension phase, CGI and SGI scores remained stable for MM pts and improved for PM pts upon switching to MD1003.

Conclusions: Results from the MS-SPI study at 4 years of follow-up indicate that 1) delayed MD1003 treatment results in higher disability over time, 2) pts show improvement when switching from placebo to MD1003, and 3) the effects of MD1003 observed in the double-blind phase are sustained over time.

Disclosure: Dr. De Seze has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Sanofi-Genzyme, Teva, Novartis, Roche, Chugai, and Alexion. Dr. De Seze has received research support from Sanofi. Dr. Edan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck, Novartis, Sanofi, Roche, LFB, Bayer AG. Dr. Edan has received research support from Novartis, Sanofi, Merck, Biogen, Roche and Teva. Dr. Moreau has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Biogen, Merck, Roche, MedDay, Teva, and Sanofi-Genzyme. Dr. Moreau has received research support from Novartis, Biogen, Merck, Roche, MedDay, Teva, and Sanofi-Genzyme. Dr. Brochet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Biogen, Genzyme, Medday. Dr. Brochet has received research support from Teva, Biogen, MedDay, Novartis, Roche, Actelion, Sanofi-Genzyme, Merck, Bayer. Dr. SEDEL has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with MedDay. Dr. SEDEL holds stock and/or stock options in MedDay stocks as part of employee’s compensation, which sponsored research in which Dr. SEDEL was involved as an investigator. Dr. Tourbah has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, MedDay, Merck Serono, Roche, Sanofi-Genzyme, Teva. Dr. Tourbah has received research support from Biogen, Novartis, MedDay, Merck Serono, Roche, Sanofi-Genzyme, Teva.