MD1003 Aids Walking Speed in Progressive MS, But Carries Risks

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by Steve Bryson, PhD |

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A woman walks as part of an exercise regimen.

High-dose biotin aided walking speed in people with progressive multiple sclerosis after 12 to 15 months as an add-on treatment, an analysis of placebo-controlled clinical trials shows.

However, the therapy failed to improve other measures of disability, and was associated with inaccurate lab test results caused by high levels of biotin in the bloodstream — which can lead to complications due to incorrect diagnoses and treatment, the researchers said.

The review study, “High-dose biotin for multiple sclerosis: A systematic review and meta-analyses of randomized controlled trials,” was published in the journal Multiple Sclerosis and Related Disorders.

Biotin, also known as vitamin B7 or vitamin H, is a compound found in food that is necessary for the body to metabolize proteins, carbohydrates, and fats.

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In MS mouse models, high doses of biotin — 10,000 times higher than the daily recommended dose — prevented the loss of myelin, the protective sheath around nerve fibers that is damaged in people with MS.

MD1003, a pharmaceutical formulation of high-dose biotin that was being developed by MedDay Pharmaceuticals, was tested in the MS-SPI Phase 3 trial (NCT02220933).  Study results suggested that one year of treatment (100 mg capsules three times a day) effectively reduced disability in people with non-active progressive MS compared with a placebo.

These findings supported the Phase 3 SPI2 trial (NCT02936037), designed to confirm MS-SPI data in a larger group of 642 progressive MS patients. However, MD1003 failed to significantly lessen disability in this trial, leading the company to stop MD1003’s clinical development.

Researchers based at the University of the Philippines conducted a review and pooled analysis of all published clinical trials evaluating high-dose biotin versus placebo to clarify its impact on people with progressive MS.

A literature search of medical databases yielded three studies that fit their criteria, covering 889 adult trial participants. In addition to SPI2, the analysis included a study (EudraCT:2013-002113-35) with 154 progressive MS patients, and another (NCT02220244) with 34 participants with progressive disease and 59 with relapsing-remitting multiple sclerosis (RRMS).

Across the studies, there were slightly more women than men, and high-dose biotin and placebo were given as an add-on treatment along with the patients’ disease-modifying therapy (DMT) regimen.

The primary outcome of this pooled analysis was composite improvement of MS-related disability (CIMSD), which was defined as a decrease of at least 0.5 points in severe disability score, measured by the expanded disability status scale (EDSS); a reduction of 1.0 EDSS points for moderate disability; or a decrease of at least 20% in 25-foot walk time (TW25) — the time it takes to walk 25 feet as quickly as possible.

Other outcomes included the individual disability components of the CIMSD, along with fatigue, visual function, finger dexterity, walking ability, cognition, clinical global impression, quality of life, and adverse events. For disability, the two trials that enrolled only progressive MS patients were evaluated.

Analyses found, after 12 to 15 months of high-dose biotin use, no significant differences in CIMSD, EDSS, or the combined EDSS-TW25 composite measure in patients with progressive MS.

However, a significant improvement was seen in the TW25 among progressive MS patients treated with biotin compared with those given a placebo.

The two progressive MS trials also measured the mean change in EDSS. Again, there was no significant change in all EDSS subdomain measures except for the sensory domain, which refers to numbness or loss of sensations.

Across all studies, no sufficient evidence was seen that high-dose biotin significantly improved visual function, fatigue, finger dexterity, cognition, walking ability, clinical global impression, or quality of life. MRI scans assessing brain lesions also showed no differences.

All trials reported adverse events. The pooled examination showed no differences between high-dose biotin and placebo.

The combined analysis reported 31 patients (4.7%) with inaccurate lab test results due to high levels of biotin in the bloodstream, which can affect certain measures involving thyroid markers, cardiac function, cancer markers, or other medications. No placebo group patients showed lab test interference.

“The substantial risk for falsely high or falsely low laboratory test results due to [high-dose biotin] intake can lead to mismanagement and [treatment-related] harm of patients who are asymptomatic or have unrelated symptoms,” the researchers wrote.

“Therefore, neurologists/MS specialists and other clinicians must consider this interference in patients with MS who are investigated for other [co-existing conditions] or are taking medications that are affected by intake of [high-dose biotin] to avoid errors in management.”

Based on “moderate quality evidence,” the team concluded, “our review found potential benefit in favor of [high-dose biotin] administered for 12 to 15 months in terms of TW25 as adjunctive treatment in patients” with progressive MS.