Author Topic: (AAN) Two reports on biotin (MD1003) in progressive MS  (Read 96 times)

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Offline agate

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(AAN) Two reports on biotin (MD1003) in progressive MS
« on: April 27, 2016, 04:29:05 pm »
A group of researchers presented two papers reporting results of clinical trials with biotin (MD1003) that show promising results.

Presented at the annual AAN conference, April 21, 2016 (Vancouver, BC):

Quote
S49.004 - 24-Month-Treatment with-MD1003 (High Doses of Biotin) in Progressive Multiple Sclerosis: Results of the MS-SPI Trial Extension Phase
 
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, 3France, 4Toulouse, France, 5Paris, France, 6Lyon, France, 7Strasbourg, France, 8Nancy, France, 9Clermont Ferrand, France, 10Caen, France, 11Nantes, France, 12Dijon, France, 13Nimes, Cedex 4, France, 14Bordeaux, France, 15Marseille, Cedex 5, France

Disclosures

  A. Tourbah:  I have received consulting and lecturing fees, travel grants from Biogen Idec, MedDay Pharmaceuticals, Sanofi-Genzyme, Novartis, Merck Serono, and Teva Pharma.. C. Lebrun-Frenay: None. M. Clanet: ; Consulting fees and scientific advisory boards from Teva, Merck Serono, Sanofi Genzyme, Biogenidec, none, none, none, none, none, Biogenidec grant to my department (salary resarch technician). C. Papeix:   teva, Novartis, servier, roche. S. Vukusic:  Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma, Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi Aventis and Teva Pharma. J. De Seze: None. M. Debouverie:  Biogen-Idec, Genzyme, Merck-Serono, Novartis The organizations mentioned in this statement did not participate in any aspects of the design, execution, analysis, or write-up of this study. O. Gout:  O.Gout received consulting and lecture fees from Allergan, Almirall, Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Sanofi, and Teva Pharma. P. Clavelou:  Travel : Genzyme, Teva, Novartis Scientific Advisory Board : Almirall, Genzyme, Novartis Speaking : Novartis, Teva, Biogen. G. Defer:  Dr Defer received personal compensation for scientific advisory board from Sanofi-Genzyme and Teva pharmaceutical Industries Ltd and has received funding for travel and/or speaker honoraria from Merck, My institution received grant from Novartis and Merck Serono for helping epidemiological and clinical research in MS. D. Laplaud: Yes, honoraria from Biogen, Novartis, Roche, Genzyme and Merck-Serono, grants from Novartis and Genzyme for financial support in basic science. T. Moreau:  I report receiving consulting fees and speaking fees from Biogen Idec, Sanofi Aventis, Genzyme, Teva Pharma, Bayer Schering, Merck Serono, Novartis and Almirall., I received personal compensation as Editor in Chief for the journal entitled La Lettre du Neurologue. P. Labauge: None. B. Brochet: consulting, serving on a scientific advisory board, speaking: Biogen, Novartis, Teva, Genzyme, Merck Serono Roche, Bayer, Unconditional grants from Biogen, MedDay, Novartis, Teva, Genzyme, Merck Serono Roche, Bayer. F. Sedel:  CEO of MedDay Pharùaceuticals, CEO and chairman of the board of MedDay Pharmaceuticals,  shareholder, co-founbder and CEO of Medday pharmaceuticals, Yes, shareholder, co-founder and CEO of Medday pharmaceuticals. J. Pelletier:  consulting, serving on a scientific advisory board, speaking: Biogen, Novartis, Teva, Genzyme, Merck Serono Roche, Bayer, Unconditional grants from Biogen, Novartis, Merck Serono.

Objectives:

To present the results at 24 months of the MS-SPI trial

Background:

High dose of Biotin, a co-enzyme for acetylCoA carboxylase, a potentially key-enzyme in myelin synthesis was investigated in progressive MS in a randomized placebo-controlled trial (MS-SPI).

Results at 12 months demonstrated improvement of a significant proportion of patients (p=0.005), decreased mean change EDSS (p=0.014) and stabilisation of the clinical global impression of change (p<0.0001).

Methods:

MS-SPI is a randomized, double-blind, placebo-controlled (2:1) trial of oral biotin 300 mg / day in patients with secondary (SPMS) or primary (PPMS) progressive MS.

Duration of the placebo-controlled was 48 weeks. The blinded phase was followed by a 12-months pre-planned extension phase where patients under placebo were switched to receive MD1003.

Patients and physicians remained blinded to the treatment administered during the first phase of the study.

Results:

The last patient will complete the study in December 2015. The database will be locked in January 2016. Full statistical analyses will be available by March 2016. Results of clinical endpoints will be presented and discussed in the context of other trials in progressive MS.

Conclusions:


The 24-month results of the MS-SPI trial will be discussed in the context of development of high doses of pharmaceutical grade biotin as a novel treatment for progressive MS.

_________________
Study supported by MedDay Pharmaceuticals

__________________________________

Quote
S49.005 - Effect of MD1003 (High Doses of Biotin) in Chronic Visual Loss Related to Optic Neuritis in Multiple Sclerosis (MS-ON): Results of a Pivotal Randomized Double Masked Placebo Controlled Study

 
Ayman Tourbah,1Carl Arndt,1Alain Vighetto,2Véronique Deburghgraeve,3Jean Pelletier,4Caroline Papeix,5Christine Lebrun-Frenay,6Pierre Labauge,7Michel Clanet,8Ahmed Toosy,9David Laplaud,10Patrick Vermersch,11Thibault Moreau,12Marc Debouverie,13Pierre Clavelou,14Olivier Heinzlef,15Jerome De Seze,16Gilles Defer,17Frederic Sedel,5Olivier Gout5

1Reims, France, 2Lyon, France, 3Rennes, France, 4Marseille, Cedex 5, France, 5Paris, France, 6Nice, France, 7Montpellier, Cedex 4, France, 8Toulouse, France, 9London, United Kingdom, 10Nantes, France, 11Lille, France, 12Dijon, France, 13Nancy, France, 14Clermont Ferrand, France, 15Poissy, France, 16Strasbourg, France, 17Caen, France

Disclosures

[see Disclosures for the abstract above]

 
Objectives:

To report the results of the MS-ON study evaluating the efficacy of MD1003 over placebo in relapsing remitting or progressive MS patients with visual loss related to optic neuropathy

Background:

MD1003 (High dose of Biotin) has recently demonstrated efficacy in decreasing progression and improving walking disability in patients with primary and secondary progressive multiple sclerosis (MS)

Methods:

This is a randomized, double-blind, multicenter, placebo-controlled (2:1) trial of oral biotin 300 mg / day in MS patients with visual loss related to optic neuropathy. All patients had at least one eye with visual acuity ETDRS score ≤ 72 for at least 6 months.

We included patients either with visual loss following an optic neuritis relapse (ON relapses, n=62) or patients with chronic progressive optic neuritis (progressive ON, n=31).

Treatment duration was 24 weeks. The primary endpoint was the mean change in 100% contrast visual acuity at “month 6” from baseline of the selected eye (defined as the eye with the worst visual acuity and showing worsening during the past 3 years). Other endpoints included visual evoked potentials, automated visual field perimetry, optic coherence tomography and patient reported outcome measures.

Results:

The last patient completed the study in August 2015. The database was locked in late September 2015. Full statistical analyses are awaited.

Baseline characteristics:

93 MS patients (62 with [optic neuritis or ON] relapses and 31 with progressive ON) from 19 sites across France and UK were randomized. Results of primary and secondary endpoints will be presented during the meeting.

Conclusions:

Results will be discussed in the context of development of high doses of pharmaceutical grade biotin as a novel treatment in MS.
________________
The study was supported by MedDay Pharmaceuticals
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

Offline agate

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From Multiple Sclerosis News Today, April 27, 2016--an article about a news release from MedDay Pharmaceuticals, which sponsored both of the studies abstracted above:

Quote
MedDay’s MD1003, a Biotin, Shows ‘Remarkable’ Efficacy in Treating Inactive but Progressive MS in Clinical Trials

  Magdalena Kegel

MedDay recently disclosed full study results from the MS-SPI and MS-ON Phase 2b/3 trials of its drug product MD1003 in patients with multiple sclerosis (MS). Specifically, the trials included people with “not active” progressive MS and those with either relapsing or progressive MS and visual loss, respectively. Data, presented at the recent American Academy of Neurology 2016 Annual Meeting in Vancouver, Canada, demonstrated better efficacy in reversing disease progression than a drug has previously achieved in not-active progressive MS.

MD1003 is a pharmaceutical formulation of high-dose biotin, a type of vitamin B. The drug, which is already commercially available in certain European countries under early access programs, has previously shown efficacy in patients with progressive MS. It acts in MS by increasing a route of cellular energy production, protecting against the breakdown of nerve cell axons. It also activates enzymes that are setting the pace on myelin repair by being involved in the production of myelin constituents.

The MS-SPI trial, focusing on not-active progressive MS, a difficult-to-treat form of the disease, explored the effects of MD1003 in 103 patients, compared to 51 others who received placebo during 12 months. The study continued in a 12-month extension phase, during which all patients received the drug but remained uninformed of whether they had been treated with MD1003 in the first phase.

MS-SPI met its primary endpoint — the proportion of patients who improved on either the Expanded Disability Status Scale (EDSS) or a timed walk test. MedDay reported improvement in 12.6 percent of patients after nine months, confirmed at 12 months, and equivalent to a reversed progression. During the same period, none of the placebo-treated patients improved.

During the extension phase, patients who had been on MD1003 from the start continued improving, with 13.2 percent of them demonstrating less disability at 18 months, and 15.4 percent at 24 months.

“Full results of the MS-SPI study are especially remarkable. This is the first time that a drug has reversed the progression of the disease in a statistically significant proportion of patients,” Professor Ayman Tourbah at CHU de Reims, France, and the studies’ principal investigator, said in a press release. “In addition, if we look at the mean Expanded Disability Scale (EDSS) change, the data compare very favorably with all previous trials that looked at the same endpoint. Almost no progression was observed in patients treated with MD1003 for 24 months, and this has never been observed before.”

Meanwhile, the MS-ON study included patients both with relapsing-remitting (RR) MS and progressive disease. The group consisted of 64 RRMS patients having a fixed visual loss after an acute inflammation of the optic nerve, and with 31 patients with progressive visual loss. During its first phase, running for 24 weeks, 65 patients received MD1003, and 28 received placebo. The first part was followed by an additional study period of 24 weeks, during which all patients received the active drug.

The study found that patients treated with MD1003 improved their eyesight slightly more than placebo-treated patients, but the difference was not statistically significant. Further analysis revealed that only the patients with progressive disease benefited from the treatment.

The studies also demonstrated good safety and tolerability data for MD1003.

“When we compare these results to other trials in progressive MS that involved more than 6000 patients overall, this is clearly the best effect size ever observed. The MS-ON trial failed to reach its primary endpoint, but this is most likely due to a majority of patients with relapsing-remitting MS in this trial. Indeed, if we focus on patients with the progressive chronic neuropathy phenotype, they seem to have benefited from the drug in the same way as patients in the MS-SPI trial. Results from both studies are therefore consistent and point to the fact that targeting neuron and oligodendrocyte metabolism represents a promising and novel disease modifying therapy approach in progressive MS, particularly in patients with a not-active progressive disease,” Professor Tourbah said.

“Taken together, these studies are very promising and provide hope for a condition that has thus far been largely intractable using treatments targeting neuroinflammation,” added Professor Bruce Cree at University of California, San Francisco, and the principal investigator in the prospective U.S. study of MD1003. “That the extension study from the SPI trial showed an apparent durability of effect suggests that high dose biotin may have disease-modifying properties in addition to its proposed role in enhancing energy metabolism.

“Furthermore, the positive impact of high dose biotin points to a new line of inquiry in understanding the pathophysiology of progressive MS,” Professor Cree concluded.

The article can be seen here.
MS Speaks--online for 13 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

 

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