MD1003, also known as 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 does MD1003 work?
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. It is also involved in the activation of enzymes required for energy production and the synthesis of myelin at the 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. MD1003 has two potential mechanisms that could have an effect on progressive MS. MD1003 can activate two acetyl-CoA carboxylases (ACC1 and ACC2), the rate-limiting enzymes in the synthesis of fatty acids required for myelin synthesis. It also activates the Krebs cycle in demyelinated axons, an essential process that results in increased energy production.
MD1003 in clinical trials
In April 2016, MedDay released full results from two Phase 2b/3 clinical trials of MD1003— MS-SPI (NCT02220933) and MS-ON (NCT02220244). The trials tested the drug in people with “not active” progressive MS and those with either relapsing or progressive MS and visual loss, respectively. 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), 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 results of the MS-SPI trial have been published in the Multiple Sclerosis Journal.
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. The results were formally published in 2018 in the journal CNS Drugs.
“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), nicknamed SPI2, investigated the effect of three 100 mg doses per day of MD1003 over placebo in the change in disability of people with progressive MS with gait impairment. 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). Topline results of the study showed that MD1003 failed to meet the primary and secondary endpoints of the study in the 642 patients tested. The results of the study were going to be presented at the 2020 American Academy of Neurology (AAN) Annual Meeting but it was canceled due to COVID-19.
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