MD1003 is a highly concentrated oral formulation of a vitamin called biotin. MedDay Pharma, a French biotechnology company, had worked to develop MD1003 as a potential treatment for progressive types of multiple sclerosis (MS), namely primary progressive (PPMS) and secondary progressive MS (SPMS).
MedDay stopped the clinical development of MD1003 in 2020, after clinical trial data showed that the therapy failed to prevent disability worsening, and was associated with inaccurate laboratory test results.
Why MD1003 was expected to work
Biotin — also known as vitamin B7, vitamin H, or coenzyme R — is a vitamin that is needed for normal cell growth. In particular, biotin is important for the function of certain enzymes that make fat molecules.
Preclinical data suggested that high doses of biotin might activate the enzymes necessary for making and repairing myelin, the fatty covering around nerve fibers that is damaged in MS. High doses of biotin may also activate the Krebs cycle (a process used to generate energy) in damaged neurons, providing them with more energy to function.
MD1003 in clinical trials
Results from two clinical trials of MD1003, both funded by MedDay, were promising. In both trials, participants were given either MD1003 (taken as a 100 mg tablet three times per day) or a placebo.
One trial, the Phase 3 MS-SPI study (NCT02220933), enrolled 154 people with “non-active” forms of progressive MS — meaning individuals who were not experiencing any disease relapses. Results showed that a greater proportion of people given MD1003 than a placebo experienced an improvement on either the Expanded Disability Status Scale (EDSS) or a timed walk test. Follow-up data from the trial’s extension study were similarly positive.
The other Phase 3 study, called MS-ON (NCT02220244), enrolled 31 people with progressive MS and 64 with relapsing-remitting MS, all of whom had vision problems due to optic neuritis (inflammation affecting the optic nerve). Results indicated that treatment with MD1003 led to improvements in vision relative to a placebo, but only among progressive MS patients.
Encouraged by these successes, MedDay launched a larger Phase 3 clinical trial called SPI2 (NCT02936037), hoping to confirm the MS-SPI study’s findings of a lessening in disability progression with MD1003 treatment. This trial enrolled 642 adults with non-active, progressive MS.
SPI2 failed to meets its goals: while a slightly greater proportion of MD1003-treated patients had lesser disability or could walk faster at one year and at 15 months than did those on a placebo (12% vs. 9%), this difference was not statistically significant, meaning that the result could be attributable to random chance.
High biotin levels in the body also can affect the accuracy of some medical laboratory tests. Despite multiple approaches taken to decrease the likelihood of such inaccuracies, more than two dozen inaccurate test results were reported over the course of the SPI2 trial. In particular, tests inaccurately suggesting hyperthyroidism, a condition caused by the overactivation of the thyroid gland, were frequent.
An analysis collectively assessing data from MS-SPI, MS-ON, and SPI2 found that, compared to placebo, biotin treatment significantly increased walking speed among patients with progressive MS.
However, the treatment did not significantly affect disability, as measured by EDSS. It also did not significantly impact visual function, fatigue, finger dexterity, cognition, MRI lesions, or quality of life. Nearly 1 in 20 treated patients (4.7%) in the trials had inaccurate test results due to high levels of biotin in the bloodstream, further supporting the decision to discontinue work on MD1003.
Last updated: Oct. 7, 2021
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