MD1003 is a highly concentrated oral formulation of biotin (also known as Vitamin H or Vitamin B7) currently under clinical investigation as a treatment for primary and secondary progressive multiple sclerosis (PPMS and SPMS). A promising treatment, it is being developed by the French biotechnology company MedDay Pharma, and thought to have both pro-myelinogenic effects and to enhance the supply of energy for nerve impulse transmission.
How MD1003 Works
Biotin is an important component of the Vitamin B12 complex and is involved in cell growth, the production of fatty acids and the metabolism of fats and amino acids, as well as the activation of enzymes required for energy production and the synthesis of myelin at cellular level. It has been hypothesized that large concentrations of biotin (300 mg/day) administered at a cellular level might be useful in the repair and regeneration of myelin sheaths, which are damaged in patients with MS. According to MedDay, MD1003 potentially influences two targets related to progressive MS: it activates acetyl-CoA carboxylases (ACC1 and ACC2), the rate-limiting enzymes in the synthesis of fatty acids required for myelin synthesis, and it activates the Krebs cycle in demyelinated axons to increase energy production.
In April 2016, MedDay released full results from two Phase 2b/3 clinical trials — MS-SPI and MS-ON — of MD1003. The trials, respectively, tested the drug in people with “not active” progressive MS and those with either relapsing or progressive MS and visual loss. Data, which was presented at the American Academy of Neurology 2016 Annual Meeting in Vancouver, Canada, demonstrated better efficacy in reversing disease progression than a drug has previously achieved in not-active progressive MS.
The MS-SPI trial (NCT02220933 and NCT02220244), conducted in France and focusing on not-active progressive MS in 154 PPMS and SPMS patients, met its primary endpoint — the proportion of patients who improved on either the Expanded Disability Status Scale (EDSS) or a timed walk test. MedDay reported improvement in 12.6 percent of patients after nine months, confirmed at 12 months, and equivalent to a reversed progression. During the same period, none of the placebo-treated patients improved. In the trial’s extension phase, patients who had been on MD1003 from the start continued improving, with 13.2 percent of them demonstrating less disability at 18 months, and 15.4 percent at 24 months.
The MS-ON study was conducted across centers in France and the U.K. It involved 93 patients with progressive visual worsening (optic neuritis), and both progressive and relapsing MS forms, treated for 24 weeks with biotin concentrate at a dose of 300mg/day. The primary endpoint was the mean change, in total study population, in 100% contrast visual acuity at six months from baseline of the diseased eye. Study results found a slight improvement, but not a significant one, in treated patients over placebo (although a greater effect was noted in progressive MS patients). A good safety profile for biotin was also confirmed.
“Full results of the MS-SPI study are especially remarkable. This is the first time that a drug has reversed the progression of the disease in a statistically significant proportion of patients,” Professor Ayman Tourbah at CHU de Reims, France, and the studies’ principal investigator, said in the April announcement of the results.
A Phase 3 study (NCT02936037) to demonstrate the effect of MD1003 300 mg over placebo in the disability of people with progressive MS with gait impairment is currently recruiting an estimate of 600 participants. Its primary objective is the proportion of participants that improve Expanded Disability Status Scale (EDSS) or time to walk 25 feet at the end of the study (15 months). The estimated primary completion date is September 2018.
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