Positive Preclinical Data with MD1003 (high dose pharmaceutical grade biotin) in X-Linked Adrenoleukodystrophy to be presented at European Committee for Treatment and Research in Multiple Sclerosis 2016
– Identification of novel molecular mechanisms of action of MD1003 in neurodegeneration
Paris, France, 14 September 2016 – MedDay, a biotechnology company focused on the treatment of nervous system disorders, today announces that new preclinical data in adrenoleukodystrophy will be presented during a poster session at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in London, UK.
The poster presentation entitled “MD1003 halts axonal degeneration and locomotor disability in a model of X-linked adrenoleukodystrophy” will take place during “Poster Session 1” on Thursday 15th September 2016 between 15.45 – 17.00 BST.
The study, which was conducted by The Neurometabolic Diseases Lab led by Professor Aurora Pujol, investigated whether MD1003 could improve the clinical signs of the disease (axonal degeneration and locomotor deficits), and aimed to identify by which molecular and biochemical mechanisms it operates.
The results show both preclinical safety and efficacy in two mouse models of X-ALD and reveal that MD1003 halted the late-onset axonopathy, which are the main contributors to disability in progressive neurodegenerative diseases such as X-ALD. Specifically, MD1003 normalized ATP and mtDNA levels in Abcd1– mice spinal cords. This induction of mtDNA is correlated to an increase of mitochondrial biogenesis factors and to inhibition of the alternative NFkB pathway (NFkB2) and downstream cytokine production. Most importantly, the treatment of MD1003 halted the locomotor disability as assessed by treadmill and bar-crossed tests in the mouse model of X-ALD (Abcd1/Abcd2 null mice).
Commenting on the results, Frederic Sedel, CEO of MedDay, said: “We are pleased with the encouraging early results from this preclinical study of MD1003 in X-linked Adrenoleukodystrophy. These data demonstrate the potential for MD1003 to provide treatment for patients with neurological diseases beyond progressive multiple sclerosis.”
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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. It 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 was obtained in a pilot open label study1 involving 23 subjects with primary and secondary progressive MS.
Following the proof of concept trial, the pivotal clinical trial called MS-SPI met its ambitious endpoint which was reversion progression in patients with not-active progressive MS, a particularly difficult –to treat population2. 12.6% of patients in the MD1003 arm showing a confirmed reversion of progression at M9 (confirmed at M12), compared to none (0%) in the placebo arm (p=0.0051). During the 12-month extension phase, patients initially on MD1003 exhibited sustained improvement. The mean EDSS decreased between M0 and M12 in the MD1003 group (-0.03) compared to progression in the placebo group (+0.13, p=0.014). During the extension phase, the values remained relatively constant compared to baseline in patients maintained on MD1003 indicating sustained efficacy. The efficacy demonstrated on EDSS was also supported by the mean clinical global impression of change scale (CGI) evaluated both by the clinician and by the patient.
A second placebo controlled trial with MD1003 in MS patients was conducted to assess the visual improvement of patients suffering from chronic visual loss resulting from optic neuritis (MS-ON). Progressive ON sub-group analysis results showed to be consistent with the MS-SPI trial, and support the potential of MD1003 in the most difficult to treat patients with progressive MS. These data also reconfirmed the good safety profile of MD1003.
X-ALD is a monogenic neurometabolic disorder caused by inactivation of the peroxisomal transporter of very long-chain fatty acids ABCD1. In mice, ABCD1 loss causes late onset axonal degeneration in the spinal cord in association with locomotor disability resembling the most common phenotype in patients, adrenomyeloneuropathy. Increasing evidence indicates that oxidative stress, bioenergetic failure and inflammation play major roles in the pathogenesis of X-ALD.
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). The Company’s most advanced pipeline candidate is MD1003 for the treatment of primary and secondary progressive multiple sclerosis. MedDay is well funded by investors including Sofinnova Partners, InnoBio, Edmond de Rothschild Investment Partners and Large Venture. For more information, please see: medday-pharma.cdmail.biz.
1Sedel, et al. Mult Scler Relat Disord. 2015 Mar;4(2):159-69
2Tourbah, et al. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study. Mult Scler. 2016 Sep 1. [Epub ahead of print]
For more information, please contact:
Consilium Strategic Communications
Mary-Jane Elliott, Jonathan Birt, Laura Thornton, Melissa Gardiner
Tel: +44 (0)20 3709 5700
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