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Update on progress of progressive MS drug MD1003

Posted: Wed Jan 14, 2015 1:05 am
MedDay provides update on progress of progressive MS drug MD1003

MedDay has provided an update on the progress of its lead product MD1003 for the treatment of primary and secondary progressive multiple sclerosis (MS), which is expected to complete its first pivotal study in Q1 2015. A second pivotal study is on track for completion by the end of 2015.... Read More -

Re: Update on progress of progressive MS drug MD1003

Posted: Sat Jan 17, 2015 2:50 am
by NHE
MD1003 appears to be 300 mg/day biotin. It's also in phase 3 for optic neuritis.

Re: Update on progress of progressive MS drug MD1003

Posted: Sat Jan 17, 2015 2:55 am
by NHE
MedDay Pharmaceuticals SAS is developing MD 1003, a concentrated formulation of D-biotin that targets a rate-limiting enzyme in myelination and could stop disease progression in advanced multiple sclerosis. Proof could come with Phase III data early next year.

D-biotin is an FDA-approved food additive. However, the daily dosage of MD 1003 is about 10,000 times the recommended daily dose of the food additive. MedDay has U.S. patents covering the method of use for high-dose D-biotin in MS. An application for the formulation has been filed. ... ced-ms-a12

Re: Update on progress of progressive MS drug MD1003

Posted: Sat Jan 17, 2015 3:02 am
by NHE
More about MD1003...
MD1003 is a highly concentrated formulation of D biotin (vitamin H). The dosage is 300 mg/day corresponding to 10,000 times the recommended daily intake of biotin. As such, MD1003 is no longer a food supplement: because of potential toxicity and new therapeutic properties at this dosage, it is an active pharmaceutical ingredient.

A patent protecting the dose and use in multiple sclerosis (MS) has been allowed in the U.S. and Europe.

Biotin is a key co-factor for enzymes involved in energy production and synthesis of myelin. Biotin has potentially two targets related to progressive MS: (1) it activates the Krebs cycle in demyelinated axons to increase energy production; (2) it activates acetyl-CoA carboxylases (ACC1 and ACC2), the rate-limiting enzymes in the synthesis of long chain fatty acids required for myelin synthesis.

The proof of concept has been obtained in a pilot open label study involving 23 subjects with primary and secondary progressive MS. Results were remarkably positive with up to 90% of the subjects who exhibited clinical improvement over time. Treatment efficacy was also assessed using electrophysiology studies and magnetic resonance spectroscopy in some patients.
Two phase 2b/3, placebo-controlled, pivotal studies are ongoing, involving 250 patients and 21 MS reference centers in France and the UK ( Identifiers: NCT02220933 and NCT02220244). ... ne/md1003/

Re: Update on progress of progressive MS drug MD1003

Posted: Tue Mar 17, 2015 12:51 am
by NHE
Related research: Biotinidase knockout mice experience acute demyelination. Treatment with biotin reverses symptoms.

Neurological deficits in mice with profound biotinidase deficiency are associated with demylination and axonal degeneration.
Neurobiol Dis. 2012 Sep;47(3):428-35.
  • Biotinidase deficiency is an autosomal recessively inherited disorder characterized by neurological and cutaneous abnormalities. We have developed a transgenic knock-out mouse with biotinidase deficiency to better understand aspects of pathophysiology and natural history of the disorder in humans. Neurological deficits observed in symptomatic mice with biotinidase deficiency are similar to those seen in symptomatic children with the disorder. Using a battery of functional neurological assessment tests, the symptomatic mice performed poorly compared to wild-type mice. Demyelination, axonal degeneration, ventriculomegaly, and corpus callosum compression were found in the brains of untreated, symptomatic enzyme-deficient mice. With biotin treatment, the symptomatic mice improved neurologically and the white matter abnormalities resolved. These functional and anatomical findings and their reversal with biotin therapy are similar to those observed in untreated, symptomatic and treated individuals with biotinidase deficiency. The mouse with biotinidase deficiency appears to be an appropriate animal model in which to study the neurological abnormalities and the effects of treatment of the disorder.

Re: Update on progress of progressive MS drug MD1003

Posted: Tue Mar 17, 2015 2:28 am
by NHE
High doses of biotin in chronic progressive multiple sclerosis: A pilot study
Multiple Sclerosis and Related Disorders, 2015
  • Background: No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis.

    Objectives: The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS.

    Study design:Uncontrolled, non-blinded proof of concept study

    Methods: 23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100–300 mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures.

    Results: In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset.

    Conclusions: These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going.

Re: Update on progress of progressive MS drug MD1003

Posted: Wed Mar 18, 2015 8:28 am
by ton
MedDay will present data from the pivotal Phase III clinical trial of progressive multiple sclerosis at the annual meeting of the AAN

The Effect of MD1003 (High Doses of Biotin) in Progressive Multiple Sclerosis will be presented at the plenary session of clinical trials at the annual meeting of The American Academy of Neurology (AAN), on Friday April 24 at 12:00 p m:
Results of a Pivotal Phase III Randomized Double Blind Placebo Controlled Study
Ayman Tourbah, MD, PhD
CHU of Reims, Reims, France

Re: Update on progress of progressive MS drug MD1003

Posted: Sun Apr 12, 2015 3:57 pm
by CureOrBust
Admittedly I have not read the following, but a quick scan showed it appeared to have a lot of background info about biotin. I am on my way pout, so will read it later myself. I thought I would share (and serve as a record for myself), sorry if the info is already posted above. ... -time.html