Author Topic: News about biotin (vitamin H), MD1003  (Read 562 times)

0 Members and 2 Guests are viewing this topic.

Offline agate

  • Administrator
  • *****
  • Posts: 9822
  • MS diagnosed 1980
  • Location: Pacific Northwest
News about biotin (vitamin H), MD1003
« on: March 16, 2015, 01:41:10 pm »
A megadose of biotin is being tried for progressive MS. Biotin, also known as vitamin H, happens to be one of the ingredients in my daily multivitamin (30mcg/day, which is 10% of the RDA).

From Multiple Sclerosis News Today, March 13, 2015:

Quote
Two Progressive MS Phase III Trials to be Presented at AAN Annual Meeting

ALISA WOODS, PHD

Myelin — the fatty substance that wraps around nerve cells — is lost in multiple sclerosis (MS). Is there any way to get it back or to stop the deterioration of myelin? Researchers at MedDay Pharmaceuticals think that their drug may provide the solution. Known as MD1003, the medication targets the process of forming myelin, called myelination. It may stop the disease from progressing.

MedDay has announced that data from the first pivotal Phase III study using MD1003, a highly-concentrated pharmaceutical-grade biotin for use in primary and secondary progressive multiple sclerosis, will be presented at the Clinical Trials Plenary Session at The American Academy of Neurology (AAN) Annual Meeting, Washington DC on Friday April 24th at 1200 EST.

Two multi-center double-blind placebo-controlled trials in progressive MS examining the effects of MD1003 will be featured. The studies have been ongoing in France and the UK. Researchers completed the first pivotal Phase III study in 150 patients in early 2015. The second study should be finished by the end of the year.

...

The D-biotin used in MD1003 is actually an FDA-approved food additive. The daily dosage of MD 1003 is approximately 10,000 times greater than the recommended daily dose of D-biotin. Biotin is also called vitamin H, and is a component of B vitamins. Biotin helps the body metabolize fats and carbohydrates, but may also play a crucial role in maintaining nervous system function.

In nerve cells that have lost myelin, MD1003 may increase energy production by activating what is known as the krebs cycle. It could also activate enzymes that help to increase the production of new myelin.

In a pilot study of 23 people with primary and secondary progressive MS, up to 90% of the participants showed clinical improvement over time. This provides hope that the treatment will be successful, but larger studies are needed both to assure that MD1003 is effective, and for regulatory approval. Following positive Phase III clinical trials the medication may be made available for prescribing and use by people with MS.

Scientists are also studying MD1003 for use in a rare neurodegenerative disorder called X-linked adrenoleukodystrophy.

MedDay is a biotechnology company based in Paris, France that develops new drugs for nervous system disorders. Frédéric Sedel, MD, PhD (Chief Executive Officer), a leading neurologist and neuroscientist started MedDay in 2011 along with Guillaume Brion, MD (Chief Operating Officer).

About the author:

Alisa G. Woods, Ph.D., MS is an Assistant Professor of the Biochemistry & Proteomics Group in the Department of Chemistry & Biomolecular Science at Clarkson University in Potsdam, NY.

The article can be seen in its entirety here.
« Last Edit: October 02, 2015, 07:06:26 am by agate »
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

  • Administrator
  • *****
  • Posts: 9822
  • MS diagnosed 1980
  • Location: Pacific Northwest
Results for experimental progressive MS therapy
« Reply #1 on: April 13, 2015, 03:57:06 pm »
More on MD1003 in Multiple Sclerosis News Today, April 10, 2015:

Quote
Results for Experimental Progressive Multiple Sclerosis Therapy

 PATRICIA SILVA, PHD
   
MedDay recently announced in a news release that it is preparing to release the design and results of its clinical trial to assess the safety and efficacy of MD1003 in primary and secondary progressive multiple sclerosis (MS) treatment. Data on the Phase III clinical trial (MS-SPI) will be presented on Friday April 24th 2015 at the Clinical Trials Plenary Session at The American Academy of Neurology (AAN) Annual Meeting in Washington DC. The results are highly anticipated, as there are still high unmet therapeutic needs for people with the progressive form of the disease.

...

Progressive MS is estimated to affect at least 40% of all MS patients. It is characterized by a gradual, steady progression of disability, leading to impairment in vision and walking, pain, fatigue, incontinence and cognitive changes. Patients usually have a poor response to treatment and there is little or no recovery. Progressive MS can be either primary, where patients develop this form of the disease from the time of diagnosis, or secondary, where patients initially experience a relapsing-remitting phase of neurological dysfunction that later evolves into a secondary progressive disease. Primary progressive MS only affects 10 to 15% of MS patients, while the majority of patients (85%) develop secondary progressive MS.

MD1003 is an experimental drug that has pro-myelinotic properties and is thought to improve the supply of energy for nerve impulse transmission. MD1003 acts by activating acetyl-CoA carboxylases (ACC1 and ACC2), which are the rate-limiting enzymes in the long chain fatty acids synthesis required for myelin formation, and by activating the Krebs cycle in demyelinated axons to increase energy production.



MS-SPI is a multi center, randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of MD1003 at a dose of 300 mg/day in patients diagnosed with progressive MS for at least 2 years prior to enrollment in the study. In total, 154 MS patients from 16 MS reference centers in France who had a baseline Expanded Disability Status Scale (EDSS) score of 4.5 to 7 were evaluated. The study was carried out for 12 months.

Patients were evaluated for the stabilization or slowing down of MS progression at nine months (M9) and 12 months (M12) after MD1003 treatment. Improvement was established as a decrease in EDSS score or an improvement of at least 20% in a timed 25-foot walk test (TW25).

“This trial was particularly ambitious. This is the first time that a study in progressive MS has evaluated the proportion of patients improved at M9 and confirmed at M12. This challenging clinical endpoint was designed during discussions with European and US regulators. We look forward to presenting the results of the trial at AAN later this month,” said the Chief Executive Officer of MedDay, Dr. Frédéric Sedel in the news release.


_______________________

Patricia Silva, PhD

Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.


The article can be seen here.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

  • Administrator
  • *****
  • Posts: 9822
  • MS diagnosed 1980
  • Location: Pacific Northwest
More on biotin
« Reply #2 on: April 22, 2015, 09:08:48 pm »
More on biotin in Multiple Sclerosis and Related Disorders, 4 (2015), "High doses of biotin in chronic progressive multiple sclerosis: A pilot study"--available here.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

  • Administrator
  • *****
  • Posts: 9822
  • MS diagnosed 1980
  • Location: Pacific Northwest
Presented at the AAN annual conference in Washington, DC:

Quote
[PL2.002] Effect of MD1003 (High Doses of Biotin) in Progressive Multiple Sclerosis: Results of a Pivotal Phase III Randomized Double Blind Placebo Controlled Study

Ayman Tourbah,1Christine Lebrun Frenay,2Gilles Edan,3Michel Clanet,4Caroline Papeix,5Sandra Vukusic,6Jerome De Seze,7Marc Debouverie,8Olivier Gout,5Pierre Clavelou,9Gilles Defer,10David Laplaud,11Thibault Moreau,12Pierre Labauge,13Bruno Brochet,14Frederic Sedel,5Jean Pelletier15

1Reims, France, 2Nice, France, 3Rennes, France, 4Toulouse, France, 5Paris, France, 6Lyon, France, 7Strasbourg, France, 8Nancy, France, 9Clermont Ferrand, France, 10Caen, France, 11Nantes, France, 12Dijon, France, 13Montpellier, France, 14Bordeaux, France, 15Marseille, France.

OBJECTIVE:

To evaluate the efficacy of Biotin 300 mg/day over placebo in patients with progressive multiple sclerosis (PMS).

BACKGROUND:

Biotin is a water-soluble 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 key-enzyme in myelin synthesis. In one previous open-label pilot study involving 23 patients, it was found that high doses of biotin (100 to 600 mg/day) resulted in progressive and sustained improvement of disability in primary and secondary PMS patients.

DESIGN/METHODS:

This is a randomized, double-blind, multicenter, placebo-controlled (2:1) trial of oral biotin 300 mg / day in patients with secondary or primary PMS with EDSS between 4.5 and 7 and evidence of EDSS progression within the past two years. Treatment duration was 48 weeks. The primary endpoint was the proportion of patients who improved at M9 and confirmed at M12, defined as decreased EDSS (by at least 1 point for EDSS ≤5.5 and .5 point for EDSS ≥6) or improved TW25 of at least 20%. Other endpoints included MSWS, CGI, % patients with stable or worsened EDSS, SF36, FIS, 9HPT.

RESULTS:

The last patient is scheduled to complete the study January 2015. Baseline characteristics: 154 subjects from 16 sites across France were randomized; mean age 51.4; mean disease duration 16.6 years; 41% had PPMS and 59% had SPMS. The mean EDSS score was 6.1. The database will be locked by March 2015. Detailed results from primary and other outcomes will be presented.

CONCLUSIONS:

This trial will evaluate the efficacy of Biotin 300 mg/d in a randomized, placebo-controlled trial. Effects of treatment with high doses of biotin in patients with PMS will be discussed in the context of future development of high doses of biotin as a novel potential treatment in PMS.

________________________
Category - MS and CNS Inflammatory Disease: Clinical Science

Session: PL02: Plenary: Clinical Trials Plenary Session (12:00 PM-1:30 PM)
Date/Time: Friday, April 24, 2015 - 12:00 pm

The abstract can be seen here.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

  • Administrator
  • *****
  • Posts: 9822
  • MS diagnosed 1980
  • Location: Pacific Northwest
From Medscape Neurology Commentary, May 1, 2015--two neurologists summarizing the results of the AAN conference presentation about biotin:

Quote
Dr Cree: Returning to progressive MS, we saw the disappointing results of the INFORMS study, another trial in primary progressive MS in which there was no benefit.  My understanding is [that the results of the biotin study in progressive MS were] positive.

Dr Krieger: That is my understanding too. This is perhaps the surprise of the meeting. This study looked at very high doses of biotin supplementation—300mg daily. In contrast, a normal biotin supplement would typically be 1 mg. They tested a dose of 300 mg of biotin daily vs placebo in secondary progressive MS.

They chose improvement in disability, as measured by the Expanded Disability Status Scale (EDSS), as the primary outcome. We know from the press release that the top-line result was met. It's a positive trial of approximately 150 patients. We are eagerly going to look at the data this afternoon, see what the side-effect profile looks like, and figure out where this could fit in in the treatment of progressive disease.

Dr Cree: It's remarkable, because typically we think about progressive trials in MS as trying to prevent worsening of disability. Here is a trial that looks at improvement in function, which is remarkable if this winds up being true. With respect to mechanism of action, are there any ideas about what this compound might be doing?

Dr Krieger: We are going to have to learn that as we go. There are a couple of hypothesized mechanisms of action. One relates to the effect of biotin on mitochondrial function and energy metabolism in the cells. Another relates to the possibility that it could stabilize lipid formation, which is obviously important in a demyelinating disease. But we don't know. And the trial is much smaller than the typical modern phase 3 trial. It's about one tenth of the size of other progressive phase 3 trials. We will have to see what the clinical impact of these data will be.

Dr Cree: It can still give hope to our patients with progressive MS.

About the two participants:

Quote
Authors
Bruce C. Cree, MD, PhD, MCR
   
Associate Professor of Clinical Neurology, Clinical Research Director, University of California, San Francisco



Disclosure: Bruce Cree, MD, PhD, MCR, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Biogen Idec; EMD Serono; Genzyme/sanofi-aventis; MedImmune; Novartis; Teva

Received research grant from: Acorda; Avanir; Biogen Idec; EMD Serono; Hoffman La Roche; Novartis
Stephen Krieger, MD
Assistant Professor of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York



Disclosure: Stephen Krieger, MD, has disclosed the following relevant financial relationships:

Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Amgen Inc.; Dendreon Corporation; Johnson & Johnson Pharmaceutical Research & Development, LLC; Medivation, Inc.; Myriad; Watson Pharmaceuticals, Inc.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

  • Administrator
  • *****
  • Posts: 9822
  • MS diagnosed 1980
  • Location: Pacific Northwest
A distributor for MD1003 (biotin) for management of MS has been named--Durbin in the UK. From Multiple Sclerosis News Today, September 25, 2015:

http://multiplesclerosisnewstoday.com/2015/09/25/new-ms-drug-distributed-global-supply-chain-distributor-durbin/
« Last Edit: October 02, 2015, 02:52:23 pm by agate »
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.