MedDay reports positive pivotal Phase III study results with MD1003 in patients with Progressive Multiple Sclerosis - Primary endpoint met with a higher proportion of patients showing an improvement in EDSS or TW25 at Month 9 and confirmed at Month 12 in the active arm (p = 0.0051) -‐ Decreased mean EDSS progression demonstrated at Month 12 (p = 0.015) - MD1003 generally well tolerated Paris, France, April 24 2015 -‐ MedDay, a biotechnology company focused on the treatment of nervous system disorders, today announced positive results from the pivotal Phase III clinical trial, MS-‐SPI, which showed evidence of the efficacy and safety of MD1003, a highly-‐concentrated pharmaceutical-‐grade biotin administered at a dose of 300 mg per day in the treatment of primary and secondary progressive multiple sclerosis, a major area of unmet medical need. The primary endpoint was met with a proportion of MS patients showing an improvement in EDSS or TW25 at Month 9 and confirmed at Month 12 (p = 0.0051). The primary endpoint was supported by evidence of a substantial decrease in the risk of disease progression. The MS-‐SPI study was 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 within the two years prior to inclusion and with EDSS ranging from 4.5 to 7. Patients with disease modifying therapy (DMT) introduced less than 3 months prior to inclusion; fampridine introduced less than 1 month prior to inclusion; or evidence of relapse or Gadolinium-‐MRI activity within the past year were excluded from the study. Patient enrolment commenced in October 2013 and was completed in January 2014 with 166 patients screened. 154 were randomized (103 in the MD1003 arm and 51 in the placebo arm -‐ randomization 2:1). Characteristics of the patients between the two patient groups demonstrated no statistical difference. There were 12 treatment discontinuations in the active arm and 8 in the placebo arm. All analyses were performed according to the intent to treat principle and as such all randomized patients were analysed according to the treatment arm they were assigned to. The primary endpoint for the study was defined as the proportion of patients who improved at 9 months (M9), with confirmation 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. Overall the primary criteria was met, with 13 MD1003-‐treated patients (12.6%) demonstrating improvement on EDSS or TW25 at M9, confirmed at M12, versus none in the placebo group (p=0.0051, Fisher’s exact test). The primary endpoint was supported by a decrease in the mean EDSS change between M0 and M12 in the whole MD1003 group (-‐0.03) compared to the whole placebo group (+0.13, p=0.015). In the MD1003 arm, 4% of patients treated with MD1003 showed EDSS progression at M9 confirmed at M12 vs 13% in the placebo group (p=0.07) which makes a decreased risk of progression of 67% in the active arm within the studied period. The overall incidence of adverse events were similar across the two groups. One patient died from suicide in the active arm, however this event was not considered to be related to the drug. An interference was noticed in some patients between high plasma concentrations of biotin and immunoassays using biotinylated antibodies and substrates. Prof. Ayman Tourbah, Principal Investigator of the study, CHU de Reims, Neurology, France, said: "We are encouraged by the outcomes of this pioneering and stringently designed MS-‐SPI trial. The rapid rate of recruitment into this multi-‐centre study demonstrates the serious need for a well-‐
tolerated drug by patients with primary and secondary progressive multiple sclerosis. The proportion of patients showing improvement after nine months and confirmed at twelve months, coupled with the decrease in risk of disease progression demonstrated here, makes MD1003 a potentially important new therapy for patients and clinicians in the field of MS.” Commenting on the results of the study, Frederic Sedel, Chief Executive Officer of MedDay, said: “These results are very encouraging. This is the first time that a drug has been able to decrease the rate of disease progression in addition to improving a significant proportion of patients with progressive MS. We look forward to the analyses of other secondary endpoints, as well as to the results of the 24 month extension phase which will provide data about the sustainability of the effect. MRI studies using conventional and non-‐conventional techniques will provide additional data about the mechanism of action. A second Phase III placebo-‐controlled trial is underway in MS patients with permanent visual loss following optic neuritis. Results are expected later this year.” The data was presented for the first time today at The American Academy of Neurology (AAN) Annual Meeting by the Principal Investigator at the Clinical Trials Plenary Session, Washington DC. The detailed data is expected to be published in a peer review journal in due course. About MD1003 MD1003 is an investigational medicine thought to have both pro-‐myelinotic 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. 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. Scientific Advisory Board Prof. Alan Thompson (Chairperson, UCL, UK); Prof. Jack Antel (McGill, Canada); Dr Robert Fox (Cleveland, USA); Prof. Reinhard Hohlfeld (Munich, Germany); Prof. Jean Pelletier (Marseille, France); Prof. Per Soelberg Sorensen (Denmark); and Prof. Ayman Tourbah (Reims, France, Principal Investigator in the study). About MedDay 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: www.medday-‐pharma.com. Reference 1
Sedel, et al. Mult Scler Relat Disord. 2015 Mar;4(2):159-‐69 For more information, please contact: MedDay Pharmaceuticals Email: contact@medday-‐pharma.com Consilium Strategic Communications Mary-‐Jane Elliott, Jonathan Birt, Ivar Milligan, Laura Thornton Tel: +44 (0)20 3709 5700 Email: medday@consilium-‐comms.com