Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial

Cree BAC, et al

Published in The Lancet Neurology

Methodology

Multicentre randomised, double-blind, placebo-controlled phase 3 trial of MD1003 300 mg/day for 12 months with 3-month confirmation in progressive MS, with confirmed EDSS or timed 25-foot walk improvement at months 12 and 15 as the primary endpoint.

Key Findings

In SPI2, 642 patients with progressive multiple sclerosis received MD1003 (high-dose biotin, 300 mg/day) or placebo for 15 months; the proportion with confirmed improvement in disability was 12% with biotin versus 9% with placebo (not significant), with no benefit on walking time or EDSS progression, and biotin caused clinically important interference with laboratory assays including falsely abnormal thyroid results.

Conclusions

High-dose biotin does not improve disability in progressive multiple sclerosis, definitively overturning promising earlier phase results, and carries a real risk of laboratory test interference.

Limitations

Fifteen-month duration may be short for progressive MS disability change; disability improvement endpoint is demanding; biotin assay interference complicated safety monitoring; results apply to a specific pharmacological dose far above nutritional intake.