Conference Coverage
WASHINGTON, DC—Biotin may result in clinical improvement among patients with progressive multiple sclerosis (MS) and decrease the risk of progression, according to a study described at the 67th Annual Meeting of the American Academy of Neurology. The drug appears not to be associated with any significant adverse events.
Many MS therapies have reduced relapses effectively but have failed to produce significant and sustained reductions in disability. In an open-label study published in 2015, patients with progressive MS who received high doses of biotin had 22% clinical improvement, mainly in the Expanded Disability Status Scale (EDSS). Ayman Tourbah, MD, PhD, Professor of Neurology at Centre Hospitalier Universitaire in Reims, France, and colleagues subsequently conducted a Phase III trial of MD1003, a highly concentrated pharmaceutical grade of biotin, at 16 MS reference centers.
Ayman Tourbah, MD, PhD
Comparing MD1003 and Placebo
Eligible participants were between ages 18 and 75, had primary or secondary progressive MS, had an EDSS score between 4.5 and 7, and had disease progression within the previous two years, as measured by EDSS. Patients were excluded from the study if they had initiated a new disease-modifying therapy during the three months before enrollment or if they had received symptomatic treatment with fampridine within one month of enrollment.
The researchers screened 166 patients and included 154 of them in a two-to-one randomization. In all, 103 patients received daily 300-mg doses of MD1003, and 51 patients received placebo. Slightly more patients in the active arm had primary progressive MS, compared with the placebo group. Also, slightly more patients were taking fampridine in the placebo group, compared with the active group. The researchers noted no other differences between the treatment arms.
The study’s primary end point was the proportion of patients with improvement at month nine that was confirmed at month 12 using EDSS or the Timed 25-Foot Walk (T25FW), compared with baseline measures. EDSS improvement was defined as a decrease of at least one point for patients with a baseline EDSS between 4.5 and 5.5, and as a decrease of at least 0.5 points for patients with a baseline EDSS between 6 and 7. T25FW was considered improved if it decreased by at least 20%, compared with baseline.
Treated Patients Had Sustained Improvement
At the end of the study, 13 patients in the active arm had met the primary end point, compared with none of the patients in the placebo arm. The difference between groups was statistically significant. Twice as many patients met the primary end point with the EDSS, compared with the T25FW. The investigators found no major differences between the group of patients treated with MD1003 and the group of patients who met the primary end point.
A secondary analysis indicated that mean EDSS improved at the initial phase of the trial for participants in the treatment arm, and their improvement was sustained throughout the study. The placebo group had an initial improvement in mean EDSS, but EDSS worsened at all subsequent time points. After 12 months, the difference between the two groups in the mean change in EDSS was statistically significant.
In addition, 13.6% of patients in the placebo group had EDSS progression that was confirmed at two subsequent visits. In contrast, 4.2% of patients receiving MD1003 had progression at month nine that was confirmed at month 12. The difference between groups was not statistically significant, however. Nevertheless, the data indicate a 67% decrease in the risk of progression for patients receiving MD1003, compared with controls, said Dr. Tourbah. Similar trends were observed for the T25FW.
The researchers found no difference in adverse events between the treatment groups. Twice as many patients in the placebo group had relapses, compared with the active arm. High doses of biotin may interfere with immunoassays that use biotinylated antibodies or substrates, however, thus requiring patients and physicians to be informed adequately.
Biotin is a water-soluble coenzyme that is thought to promote myelination and enhance energy supply. “High doses of biotin may feed the Krebs cycle to increase adenosine triphosphate synthesis and energy production, thus possibly reversing virtual hypoxia and protecting neurons from degeneration,” said Dr. Tourbah.
—Erik Greb