MedDay reports positive pivotal Phase III study results with MD1003 in patients with Progressive Multiple Sclerosis

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. The study demonstrated 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 (p=0.0051, Fisher’s exact test) in the intent to treat population with 12.6% of patients 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 primary endpoint was supported by secondary analyses showing evidence for a decrease in the risk of disease progression. 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=0.015). 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. The study was not prospectively powered to reach significance for this secondary endpoint.

MD1003 was well tolerated. The overall incidence of adverse events was similar across the two groups. One patient died from suicide in the active arm, however this event was not considered as related to the drug. In 5 patients, abnormal laboratory data indicated that MD1003 may affect the results of immunoassays which use 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 fact that no patient in the placebo group met the primary endpoint indicates that the study bar was designed to be very high. The rapid rate of recruitment into this multi-centre study illustrates the serious need for a well-tolerated drug by patients with primary and secondary progressive multiple sclerosis. The significant proportion of patients showing improvement 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: “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 and MRI studies which might provide additional data about the mechanism of action. Furthermore, 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. Results from this trial are expected later this year and based on previous discussions with regulators we intend to investigate a drug filing thereafter.”

Data presentation and webcast

The data were 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.

A webcast, including a presentation by the Principal Investigator of the study, will take place on Tuesday 28th April at 1200 EST / 1700 CEST. To view the webcast, please call:

UK: +44 207 192 8000

France: +33 176 700 794

USA: +1 866 966 1396

Conference ID: 36018525

Once you have registered your name with the operator, to join the web portion, please visit:

https://webconnect.webex.com/webconnect/onstage/g.php?MTID=e76b5ae67f77c98452bbf31b238d235f4

About MS-SPI:

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.

There were 12 treatment discontinuations in the MD1003 arm and 8 in the placebo arm. All analyses being performed according to the intent to treat (ITT) principle, all randomized patients were analysed according to the treatment arm they were assigned to.

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.

About MD1003

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. 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.

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

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

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Contact information

MedDay Pharmaceuticals
Email: contact@medday-pharma.com
or
Consilium Strategic Communications
Mary-Jane Elliott, Jonathan Birt, Ivar Milligan, Laura Thornton
Tel: +44 (0)20 3709 5700
Email: medday@consilium-comms.co