– Second placebo controlled study with MD1003 in Multiple Sclerosis patients
– Focus on patients with chronic visual loss following optic neuritis (ON)
– Progressive ON sub-group analysis results consistent with ongoing MS-SPI trial and support potential of MD-1003 in the most difficult to treat Progressive Multiple Sclerosis patients
– Latest results confirm the very good safety profile of MD1003
Paris, France, 1 December 2015 – MedDay, a biotechnology company focused on the treatment of nervous system disorders, today announces results from a second placebo-controlled study of its lead investigational therapy MD1003, a highly-concentrated pharmaceutical-grade biotin administered at a dose of 300 mg /day, in the treatment of Progressive Multiple Sclerosis.
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.
The MS-ON results confirmed the very good safety profile of MD1003.
Commenting on the MS-ON results, Prof. Ayman Tourbah, Principal Investigator in the study, CHU de Reims, Neurology, France, said: “The MS-ON provides interesting data suggesting that MD1003 has an impact in patients with progressive optic neuritis. With the lack of a similar signal in the treatment of non-progressive optic neuritis, the study confirms that the under-treated progressive multiple sclerosis population might be the most appropriate target for MD1003. This is also consistent with the positive MS-SPI results reported earlier this year in a different population of MS patients with progressive lower limbs spasticity.”
Frédéric Sedel, CEO of MedDay, commented:
“The MS-ON data provide a better view about the future positioning of MD1003. MedDay will now pursue the development and file MD1003 only in progressive forms of MS, where there is a particular need for a disease modifying therapy and no drug approved so far. Given the original and unique mode of action of MD1003 that targets myelin and energy metabolism, MD1003 could complement other treatment strategies targeting inflammation on the immune system including immunosuppressants or immunomodulatory drugs.”
The MS-ON study is a randomized 2:1, double-blinded, placebo-controlled study conducted in 20 MS reference centres in France and UK. Treatment duration was 24 weeks followed by a pre-planned ongoing extension phase where the placebo was switched to the active. MedDay included MS patients either with visual loss in the last three years either following an optic neuritis relapse (ON relapses, n=62) or in the context of chronic progressive optic neuritis (progressive ON, n=31). All patients had at least one eye with visual acuity ETDRS score ≤ 72 (visual acuity below 5/10 in decimals) for at least 6 months.
The primary endpoint was the mean change in 100% contrast visual acuity at “month 6” from baseline of the diseased eye defined as the eye with the worst visual acuity and showing worsening during the past 3 years.
Other endpoints included 5% contrast visual acuity of all eyes, retinal nerve fiber layer thickness (RNFL) of all eyes measured by optic coherence tomography, visual evoked potentials, automated visual field perimetry, and patient reported outcome measures.
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 followed by a pre-planned 12 months- ongoing extension phase where the placebo was switched to the active.
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). At baseline 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.
The primary endpoint was met (p=0.0051, Fisher’s exact test) in the intent to treat population with 13 patients (12.6%) in the MD1003 arm showing an improvement of EDSS (Expanded Disability Status Scale) or TW25 (a timed 25-foot walk) at Month 9, confirmed at Month 12, compared to none of the patients (0%) in the placebo arm.
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.
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 (p<0.0001 and p=0.0094, respectively).
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 study1 involving 23 subjects with primary and secondary progressive MS.
About progressive MS
MS is the most common disabling neurological disease among young adults, with first symptoms typically manifesting between 20 and 40 years of age. In the majority (85%) of cases, 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, individuals experience a gradual worsening of neurological disability leading to problems with vision, walking, incontinence, cognitive changes, fatigue, and pain. Primary progressive MS (PPMS) characterized by disease progression from onset is less common, affecting 10–15% 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.
Scientific Advisory Board
MedDay is a privately held biotechnology company developing new drugs for nervous system disorders. The company was founded in 2011 by Frédéric Sedel, MD, PhD (Chief Executive Officer); and Guillaume Brion, MD (Chief Operating Officer). In April 2013, InnoBio, a biotechnology fund managed by BPIFrance, and Sofinnova Partners together invested in MedDay. The Company’s most advanced pipeline candidate is MD1003 for the treatment of primary and secondary progressive multiple sclerosis. For more information, please see: medday-pharma.cdmail.biz.
1Sedel, et al. Mult Scler Relat Disord. 2015 Mar;4(2):159-69
For more information, please contact:
Consilium Strategic Communications
Mary-Jane Elliott, Jonathan Birt, Laura Thornton
Tel: +44 (0)20 3709 5700