Date: 2016-04-21
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the American Academy of Neurology annual meeting
Company: Medday (France)
Product: MD1003 (high doses of pharmaceutical-grade biotin)
Action
mechanism: vitamin. MD1003 is an active pharmaceutical ingredient administered at a dose of 300 mg /day has patent protection in EU and US for dose and use in multiple sclerosis. MD1003 has a mode of action which 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.
MD1003’s proof of concept has been obtained in a pilot open label study involving 23 subjects with primary and secondary progressive MS. 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.
Disease: chronic visual loss resulting from optic neuritis in multiple sclerosis
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country: France, UK
Trial
details: The purpose of this study is to demonstrate the superiority of MD1003 over placebo in the visual improvement of patients suffering from chronic visual loss resulting from multiple sclerosis related optic neuritis. (NCT02220244 )
Latest
news: * On April 21, 2016, MedDay announced full study results from the MS-ON trial which will be presented at the 2016 American Academy of Neurology Annual Meeting. The MS-ON study was designed to investigate whether MD1003 could accelerate recovery following incomplete remission of an acute relapse and/or specifically improve patients with progressive disability. For this purpose, the study enrolled patients with fixed visual loss (?6 months) following an acute optic neuritis in the previous three years (non-progressive chronic optic neuropathy, n=62) together with MS patients showing progressive visual loss assessed at two different visits in the previous three years (progressive optic neuropathy, n=31). The placebo-controlled phase was 24 weeks (65 patients received MD1003 and 28 received a placebo) followed by a 24-week extension phase during which all patients (n=92) received MD1003. The primary endpoint was the mean change from baseline in 100% contrast visual acuity (VA) at 24 weeks of the selected eye (defined as the eye with the worst visual acuity and acute or progressive worsening within the three years prior to inclusion). Final results showed that, overall, patients who received MD1003 improved slightly more than patients who received the placebo (average of 3.1 letters in the MD1003 arm versus 1.8 letters in the placebo arm). However the difference did not reach statistical significance. Patients in both the MD1003 and placebo groups continued to improve during the extension phase (mean of 4.25 letters in the initial MD1003 arm versus 4.0 letters in the placebo arm switched to MD1003).
Prospectively defined subgroup analyses identified that only patients with progressive ON may benefit from MD1003, while no effect was observed in the largest subgroup of patients with non-progressive ON following a relapse. During the placebo-controlled phase, patients in the progressive chronic ON subgroup who received MD1003 improved by a mean of 2.75 letters, while patients who received the placebo worsened by a mean of -1.45 letters. During the 24-week extension phase, patients who were given MD1003 continued to improve (to a mean of 4.55 letters) while those who were initially on placebo stopped worsening after they were switched to the active drug (mean of -1.2 letters at 48 weeks).
* On December 1, 2015, MedDay announced results from a second placebo-controlled study of its lead investigational therapy MD1003. The MS-ON study was designed to investigate the superiority of MD1003 over placebo in the visual improvement of patients suffering from chronic visual loss resulting from optic neuritis (MS-ON). The trial included patients with progressive worsening visual loss (progressive ON, n=31) as well as patients with permanent but non-progressive visual loss following an optic neuritis relapse (non-progressive ON, n=62). Treatment duration was 24 weeks. The primary endpoint was the mean change, in the total study population, in 100% contrast visual acuity (VA) at six months from baseline of the diseased eye defined as the eye with the worst visual acuity and acute or progressive worsening within the 3 years prior to inclusion.
Patients who received MD1003 tended to improve slightly more than patients who received the placebo (3 letters mean improvement in the MD1003 arm versus 1.8 letters in the placebo arm) however the difference did not reach statistical significance and overall the study did not meet its primary endpoint.
Prospectively defined subgroup analyses identified that only patients with progressive ON might have benefited from MD1003 while no effect was observed in the largest subgroup of patients with non-progressive ON following a relapse:
• In the subgroup of patients with progressive ON, 100% contrast VA of the diseased eye improved by a mean of 3 letters in the active arm vs worsening by 1.5 letters in the placebo arm. The evolution of other important endpoints was consistent with the improvement of 100% contrast VA.
• MD1003 had no effect at all in the subgroup of patients with non-progressive ON subsequent to a relapse: the 100% contrast visual acuity improved by 3 letters in both active and placebo arms.
