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Concentrated Biotin Improves Survival in Multiple Sclerosis Trial

Pivotal phase III data to be presented at neurology meeting

The primary endpoint has been met in a pivotal phase III study of MD1003, a highly concentrated pharmaceutical-grade biotin administered at a dose of 300 mg/day, in the treatment of patients with primary progressive multiple sclerosis (PPMS).

Detailed data will be presented April 24 at the American Academy of Neurology’s annual meeting, to be held in Washington D.C.

The MS-SPI trial was a randomized, double-blind, placebo-controlled study of MD1003 300 mg/day in patients with progressive MS who had demonstrated progression during the 2 years prior to enrollment. A total of 154 patients with baseline EDSS scores of between 4.5 and 7.0 were enrolled at MS reference centers in France. The duration of treatment was 1 year.

The study’s primary endpoint was the proportion of patients who improved at 9 months, with confirmation at 12 months. Improvement was defined as either a decrease in the Expanded Disability Status Scale (EDSS) (by at least 1 point for a baseline EDSS of 5.5 or less, and by at least 0.5 points for a baseline EDSS of 6.0 or more) or an improvement in TW25 (a timed 25-foot walk) of at least 20%. The comparison for each outcome was the best EDSS and TW25 scores obtained at the screening and randomization visits.

The study’s main secondary endpoints evaluated the effect of MD1003 in stabilizing or slowing down the rate of disease progression. These endpoints include the change in EDSS between month 0 and month 12; the proportion of patients with progression at month 9, confirmed at month 12; and the change in TW25.

MD1003 is an investigational medication thought to have pro-myelinotic effects and to enhance the supply of energy for the transmission of nerve impulses. According to its manufacturer (MedDay Pharmaceuticals), MD1003 has a mode of action that potentially influences two targets related to progressive MS: 1) it activates acetyl-CoA carboxylases (ACC1 and ACC2), the rate-limiting enzymes in the synthesis of fatty acids required for myelin synthesis; and 2) it activates the Krebs cycle in demyelinated axons to increase energy production.

Proof-of-concept data for MD1003 were obtained in a pilot open-label study involving 23 subjects with primary and secondary progressive MS. The results were positive, with up to 90% of subjects exhibiting clinical improvement over time. Treatment efficacy was also assessed using electrophysiology studies and magnetic resonance spectroscopy. The results were published this year in the Journal of Multiple Sclerosis and Related Disorders.

MS is the most common disabling neurological disease among young adults, with first symptoms typically manifesting between 20 and 40 years of age. In most cases (85%), patients experience an initial phase of relapsing-remitting neurological dysfunction (RRMS), which typically evolves into a secondary progressive disease at a later point in the clinical course (SPMS). Once MS is in the progressive phase, patients experience a gradual worsening of neurological disability leading to problems with vision, walking, incontinence, cognitive changes, fatigue, and pain. PPMS, characterized by disease progression from onset, is less common, affecting 10% to 15% of patients.

Despite these different initial clinical phenotypes, the time to reach certain disability milestones and the ages at which the milestones are reached are similar for patients with PPMS and SPMS. Recent guidelines have therefore proposed to group PPMS and SPMS within a single entity called “progressive disease.” The overall prevalence of patients with progressive disease is estimated to be at least 40% of all MS patients.

Source: MedDay Pharmaceuticals; April 17, 2015.

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