Washington, DC—Patients with primary and secondary progressive multiple sclerosis (MS) showed improvements in standard measures of physical and neurologic disability after taking high doses of biotin (300 mg daily) for
1 year, according to results of a phase 3 clinical trial presented at the 2015 annual meeting of the American Academy of Neurology.
“The primary end point of this study was the proportion of patients who improved at month 9 and confirmed at month 12 [P = .005],” said Ayman Tourbah, MD, PhD, CHU de Reims, Hospital Maison Blanche and Faculté de Médecine, URCA, in Reims, France. “That primary end point was met, and supportive analyses indicated a decreased risk of progression in patients under MD1003 [biotin].”
A disabling, inflammatory, and demyelinating disease of the central nervous system, MS often begins with a relapsing-remitting period that is followed several years later by a secondary phase, according to Dr Tourbah. In primary onset progressive MS, however, the disease progresses from onset, with patients experiencing gradual disease worsening. Although past treatments have demonstrated efficacy on patients with relapsed disease corresponding to the inflammatory component of the disease, the treatments have failed to show significant and sustained impact on disability, which is mostly related to axonal loss and neurodegeneration.
According to Dr Tourbah, biotin, a water-soluble vitamin, acts as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acid synthesis.
“Biotin is thought to act in MS through 2 possible mechanisms,” Dr Tourbah explained. “On one hand, it promotes myelination by activating acetylCoA carboxylase, a potentially key enzyme in myelin synthesis….On the other hand, high doses of biotin may feed the Krebs cycle to increase ATP [adenosine triphosphate] synthesis and energy production.”
In other words, biotin has the potential to protect neurons from degeneration while increasing energy supply to oxygen-deprived cells in a state of virtual hypoxia.
After positive results came from a 23-patient pilot study, researchers initiated MS-SPI, a randomized, double-blind, multicenter, placebo-controlled trial, to study the efficacy of biotin over placebo in progressive MS-related myelinopathy.
A total of 154 patients with a baseline Expanded Disability Status Scale (EDSS) score of between 4.5 and 7 were enrolled from 16 MS reference centers across France. Over the course of 1 year, high-concentrated, pharmaceutical-grade biotin (MD1003) was taken orally at a total daily dose of 300 mg by 103 patients in the active arm. The remaining 51 patients were given placebo. According to Dr Tourbah, “MD1003 has no taste and no color, and thus cannot be recognized by patients.”
The primary end point of the study was the proportion of patients who improved at month 9 and confirmed at month 12 using either EDSS or a timed 25-foot walk (TW25) compared with baseline measures. EDSS was considered improved if it decreased by at least 1 point from baseline EDSS ≤5.5 and 0.5 points for EDSS ≥6. TW25 was considered improved if it decreased by at least 20% compared with baseline measures.
At the end of the study, 13 patients in the active arm met the primary end point, whereas no patients did so in the placebo arm. According to Dr Tourbah, this difference was significant.
“The active-treated arm showed mean change in EDSS that improved at the initial phase and remained improved throughout the duration of the study,” noted Dr Tourbah. “Concerning the placebo group, after the initial phase where the mean EDSS decreased, it then worsened at all the other time points of the study.…After 12 months, the difference between the 2 groups in the mean change in EDSS was statistically significant. Overall, this shows that patients under MD1003 not only did not progress, but they even slightly improved.”
Although twice as many patients met the primary end point with the EDSS than with the TW25 end point, Dr Tourbah still interpreted the latter’s measures as indicative of the same positive trend.
“Patients under placebo showed worse progression than patients under MD1003,” said Dr Tourbah. “The difference [with TW25] was not statistically significant, but this is probably due to large variations in measure.”
Finally, there were no major differences between groups concerning the most frequent adverse events, including infections, nervous system disorders, or gastrointestinal disorders. Although both arms had patients with relapsed disease, twice as many patients had relapsed disease in the placebo group than in the active treatment arm.
“The primary end point, which was the percentage of patients who improved under high doses of biotin, was met. The safety profile between groups was similar,” concluded Dr Tourbah. “In the active arm, 12.6% of patients improved over a year, and supportive analyses showed a decreased risk for progression in patients under MD1003. This study supports the fact that under MD1003 and as compared with placebo, a significant proportion of patients improve and fewer patients worsen.”