MedDay reports additional positive data from Phase III trial of MD1003 to treat progressive multiple sclerosis

The data, to be announced on Saturday 20th June at The 1st Congress of the European Academy of Neurology (EAN), shows an improvement of the Clinical Global Impression of change observed after 12 months of treatment with MD1003 and confirms the positive results presented at the American Academy of Neurology in April 2015.

The Clinical Global Impression of change is a 7 point scale that requires the clinician to assess how much the patient’s illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. During the MS-SPI trial, the Clinical Global Impression of change has been assessed by the clinician (clinician global impression, CGI) as well as by the patient (subject global impression, SGI) after 12 months of treatment. Mean CGI and SGI scores assessed at month 12 were statistically significantly better in the intervention group compared with the placebo group.

These important results confirm the previously reported data of MS-SPI where the primary endpoint was defined as the proportion of patients who improved either on EDSS or on timed 25-foot walk (TW25) at M9, with a confirmation of the improvement at 12 months (M12) was met (p=0.0051).

The mean change of EDSS between M0 and M12 decreased in the MD1003 group (-0.03) compared to progression in the placebo group (+0.13, p=0.014). In the MD1003 arm, only 4% of patients treated with MD1003 exhibited EDSS progression at M9 confirmed at M12 vs 13% in the placebo group (p=0.07), which equates to a 67% decreased risk of progression in the active arm within the studied period.

Commenting on these new results, Prof. Ayman Tourbah, Principal Investigator in the study, CHU de Reims, Neurology, France, said: "Results on CGI and SGI confirm the clinical meaningfulness of the primary and secondary endpoints based on walking assessment. The fact that both CGI and SGI improved very significantly in the active arm compared to the placebo adds consistency to the results."

Frederic Sedel, Chief Executive Officer of MedDay, added: "We are pleased to announce further positive findings which confirm the promising MD1003 Phase 3 data announced earlier this year at AAN. MD1003 remains the only drug to date that has demonstrated an ability to decrease the rate of disease progression and improve a significant proportion of patients with progressive MS.

"A second Phase III placebo-controlled trial is underway looking at the effect of MD1003 in MS patients with permanent visual loss following optic neuritis and we look forward to announcing data from this trial later this year and potentially investigating a drug filing thereafter."

The MS-SPI study is a randomized 2:1, double-blinded, placebo-controlled study conducted in 16 MS reference centres in France. Treatment duration was one year.

The patient population was defined as patients suffering from primary progressive Multiple Sclerosis (PPMS) or secondary progressive Multiple Sclerosis (SPMS) with EDSS progression in the two years prior to inclusion and with EDSS ranging from 4.5 to 7.

Patients excluded from the study included those with disease modifying therapy (DMT) introduced in the 3 months prior to inclusion, patients with fampridine introduced in the month prior to inclusion, or patients with evidence of relapse or Gadolinium-MRI activity within the past year.

Patient enrolment commenced in October 2013 and was completed in January 2014 with 166 patients screened and 154 patients randomized (103 in the MD1003 arm and 51 in the placebo arm). There were no statistically significant differences in the characteristics of the patients in the two patient groups.

The primary endpoint of the study was defined as the proportion of patients who improved at 9 months (M9), with a confirmation of the improvement at 12 months (M12). Improvement was defined as either a decrease in EDSS (by at least 1 point for baseline EDSS =5.5 and 0.5 points for EDSS =6) 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 randomisation visits.

MD1003 is an investigational medicine thought to have both pro-myelinogenic effects and to enhance the supply of energy for nerve impulse transmission. 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 some clinical improvement over time. Treatment efficacy was also assessed using electrophysiology studies and magnetic resonance spectroscopy.