Biotin Trial in SPMS and PPMS

[Apollo]

Please note this very successful trial involved only 23 patients! If you are a SPMSer or PPMSer thinking about adding a large amount of Biotin to your supplements please speak with your doctor first. We will learn more about this trial in April when the company presents at the AAN meeting. Right now, it looks exciting.

http://finance.yahoo.com/news/medday...070000161.html

Quote, " MD1003 is a highly-concentrated pharmaceutical-grade biotin. The dosage is 300 mg/day corresponding to 10,000 times the recommended daily intake of biotin. As such, MD1003 is an active pharmaceutical ingredient and has patent protection in EU and US for dose and use in multiple sclerosis. 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 acetyl-CoA carboxylases (ACC1 and ACC2), the rate-limiting enzymes in the synthesis of long chain 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 study involving 23 subjects with primary and secondary progressive MS. Results were positive with up to 90% of subjects exhibiting clinical improvement over time." End Quote.

[myoak]

The Phase 3 trail involving 150 patients will be reported on at the AAN meeting Friday April 24.
The report MAY hold bombshell good news of progressive MSers improving on Biotin!

We will soon know.

[myoak]

GREAT NEWS!!! HUGE SUCCESS!!!


MedDay announces its pivotal Phase III study of MD1003 in patients with Progressive Multiple Sclerosis meets primary endpoint

~ Detailed Phase III data will be presented at AAN Annual Meeting in Clinical Trials Plenary Session on April 24th 2015 ~

April 17, 2015 04:00 AM Eastern Daylight Time
PARIS--(BUSINESS WIRE)-- "MedDay, a biotechnology company focused on the treatment of nervous system disorders, today announces that the primary endpoint was met in its pivotal clinical trial MS-SPI. MS-SPI investigated the efficacy and safety of MD1003, a highly-concentrated pharmaceutical-grade biotin administered at a dose of 300 mg/day, in the treatment of progressive multiple sclerosis.

The primary endpoint for the study was defined as the proportion of patients who improved at 9 months, with confirmation at 12 months.

Detailed data will be presented for the first time at the Clinical Trials Plenary Session at The American Academy of Neurology (AAN) Annual Meeting, Washington DC, on Friday April 24th at 1200 EST.

This treatment has every reason to believe it will work across the spectrum of MS; SPMS, PPMS, and RRMS!

[ActiveMSers]

This does appear darn exciting! - Dave

From Reuters:

French firm's drug succeeds in pivotal trial for progressive MS

LONDON, APRIL 17

(Reuters) - An experimental drug comprising of a high-dose formulation of the food additive biotin has successfully helped patients with progressive multiple sclerosis in a major clinical trial, its French maker said on Friday.

Biotin, also known as vitamin H, is already an approved food additive but the pharmaceutical-grade dose used in biotech company MedDay's drug MD1003 is 300 mg a day, which is 10,000 times the recommended daily food intake.

While there have been a number of recent advances in the treatment of relapsing-remitting multiple sclerosis (MS), there are currently no effective treatments to slow or stop the gradual increase in disability in people with progressive MS.

The progressive form the disease affects around 40 percent of MS patients.

MedDay said a pivotal Phase III study with MD1003 met its goal of improving disability scores in patients after nine months and one year of treatment, potentially paving the way for the medicine to reach the market next year.

Full details of the study results will be present at the annual meeting of the American Academy of Neurology in Washington on April 24.

http://www.reuters.com/article/2015/...0XD2AO20150417

[ActiveMSers]

For a detailed look at the drug and trial, check out MS News Today's article. The double blind placebo trials going on now will be especially telling. - Dave

MedDay, a Paris, France based biotechnology company specializing in treatment of neurological disorders, has released more information regarding the design of its (MS-SPI) clinical trial that is investigating the efficacy and safety of the investigational medicine MD1003 in treatment of primary and secondary progressive multiple sclerosis (MS).

pederwabergProgressive MS is a serious and severely disabling condition with a high unmet medical need,” says Dr. Peder Walberg, CEO of Medical Need, a company that identifies and satisfies unmet medical needs of individual patients and / or situations in health care, in close collaboration with research institutions, industrial partners, health care professionals, patient organizations and other key stakeholders. Dr. Walberg observes that “MD-1003 has shown great promise for these severely affected patients which currently have a very poor prognosis and may represent a significant break-through in the treatment of progressive MS.”

MD1003 is a highly-concentrated pharmaceutical-grade biotin (vitamin H) which at a dosage of 300 mg/day corresponds to 10,000 times the official recommended daily intake (RDA) for biotin. At such doses, MD1003 is no longer considered a food supplement because of potential toxicity and its new therapeutic properties at this dosage recategorize it as an active pharmaceutical ingredient.

http://multiplesclerosisnewstoday.co...ple-sclerosis/

[undisclosEd]

I was just reading about this on a message from MS-UK that I received this morning. This is the most exciting news that I have heard yet, especially considering the fact that it is a Trial III report, and the drug company MedDay is in France and already has US patents for the drug. The drug is Biotin, also identified as vitamin H.

Find the headline that reads:

Drug succeeds in trial (17/04/15)

Here is the link, I hope that it works.

http://www.ms-uk.org/MSnews

[ActiveMSers]

MedDay announces its pivotal Phase III study of MD1003 in patients with Progressive Multiple Sclerosis meets primary endpoint

~ Detailed Phase III data will be presented at AAN Annual Meeting in Clinical Trials Plenary Session on April 24th 2015 ~

April 17, 2015 04:00 AM Eastern Daylight Time
PARIS--(BUSINESS WIRE)--MedDay, a biotechnology company focused on the treatment of nervous system disorders, today announces that the primary endpoint was met in its pivotal clinical trial MS-SPI. MS-SPI investigated the efficacy and safety of MD1003, a highly-concentrated pharmaceutical-grade biotin administered at a dose of 300 mg/day, in the treatment of progressive multiple sclerosis.

“The trial design and dosing were discussed with US and European regulators and we are pleased the results demonstrate evidence of improvement at one year in patients with progressive worsening MS”

The primary endpoint for the study was defined as the proportion of patients who improved at 9 months, with confirmation at 12 months. Detailed data will be presented for the first time at the Clinical Trials Plenary Session at The American Academy of Neurology (AAN) Annual Meeting, Washington DC, on Friday April 24th at 1200 EST.

"We are encouraged that the primary endpoint was met despite the very high bar for treatment response. This result, which will be disclosed at AAN on April 24th along with supportive analyses and safety data, suggests that MD1003 could be an important and efficacious treatment for primary and secondary progressive multiple sclerosis," said Prof. Ayman Tourbah, Principal Investigator of the study, CHU de Reims, Neurology, France.

"The trial design and dosing were discussed with US and European regulators and we are pleased the results demonstrate evidence of improvement at one year in patients with progressive worsening MS,” said Frédéric Sedel, MD, Chief Executive Officer of MedDay.

About MS-SPI

MS-SPI is a randomized, double-blind, multicenter, placebo-controlled (2:1) trial of MD1003, 300 mg/day, in patients with progressive MS who have demonstrated progression in the two years prior to enrolment.

A total of 154 patients with a baseline EDSS (Expanded Disability Status Scale) score of between 4.5 and 7 were enrolled from 16 MS reference centers across France. Treatment duration was one year.

The primary endpoint for the study was defined as the proportion of patients who improved at nine months (M9), with confirmation 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.

The main secondary endpoints evaluate the effect of MD1003 in stabilizing or slowing down the rate of progression. These endpoints include the change in EDSS between M0 and M12, the proportion of patients with progression at M9 confirmed at M12 and the change in TW25.

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.

Full session details and data presentation listings for the 2015 Annual Meeting can be found through the AAN website: www.aan.com/conferences/2015-annual-meeting.

About MD1003

MD1003 is an investigational medicine thought to have both pro-myelinotic 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 study involving 23 subjects with primary and secondary progressive MS. Results were positive with up to 90% of subjects exhibiting clinical improvement over time. Treatment efficacy was also assessed using electrophysiology studies and magnetic resonance spectroscopy. Results were published this year in the Journal of Multiple Sclerosis and Related Disorders. For more information on the study, please see: http://www.msard-journal.com/article...006-1/abstract.

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.

[myoak]

MD1003 Biotin HIGHLIGHTS

“First time a drug has decreased the rate of disease progression in addition to improving a significant proportion of patients with progressive MS.

“ ….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.

“ …only 4% of patients treated with MD1003 exhibited EDSS progression at Month 9 confirmed at Month 12 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.”

IMO, there is no reason to believe Biotin will not show similar improvements in RRMS, also.

This trial involved 154 people for 12 months. It will be exciting to see the results of more people, longer duration, and all forms of MS on MD1003, Biotin.

This is the best news I've seen in MS for a long, long time!

[Mouse]

Hold yer horses..

Whilst this sounds like fabulous news (and I really hope it is) this data has not yet been published or peer-reviewed. We have to wait & see.

Personally, I think the use of the 67% figure is very misleading.

4% of the Biotin-treated patients and 13% of the placebo group progressed.

If we do the maths - originally there were 103 patients in the treatment group, and 51 taking placebo. 12 patients dropped out of treatment, and 8 dropped out of placebo - leaving 91 taking biotin and 43 taking sugar pills.

Of these groups, 4% of 91, i.e. 4 patients progressed on the biotin and 13% of 43, i.e. 7 patients progressed on the placebo.

These numbers sound far less convincing.

The difference between 4 and 7 from treatment groups of this size give a p-value of 0.07. This is not a statistically significant difference between the two treatment groups.

It is very common for companies for overstate their results before the data has been rigorously analysed and peer reviewed, and I would hate for anybody to get their hopes up based on this data released by the company themselves.

[ActiveMSers]

Mouse is spot on (are you the same Mouse as often featured at the site below?). You took the words right out of my mouth. "Over-hyped" is how this result is best described. Leading MS prof at MS Research breaks it down here:

http://multiple-sclerosis-research.b...is+Research%29

[Mouse]

No, I'm not Prof Baker, but I'm glad his group agrees!

[I'm a scientist, recovering academic & I teach experimental design, scientific rigour, ethics & welfare in research involving the use of animals, hence 'Mouse'.]

[myoak]

My bad if I contributed to “over-hyping” the Biotin News. If there is one thing we all benefit from it is a critical look at presentations by drug companies. Often because of time constraints I post using direct quotes when commentary should be made for context.

The first point is that this Biotin trial was very small, 154 began and twenty of those dropped out leaving 134. There was no effort by the company or anyone else to disguise the number of participants. Everyone should understand this was a small trial.

4% experienced disease progression in the Biotin group of 91 (N = 91) and 13% experienced disease progression in the placebo group (N= 43). The absolute risk reduction was 9% and the relative risk reduction was 67%.

It is easy to get confused looking only at relative risk reduction. However, listing relative risk reduction of disease progression is the common practice with all MS meds. It tends to make them look better than they actually are, IMO.

Let’s keep in mind that the biotin trial figures were given at one year. Below are figures from a two year trial of teriflunomide, Aubagio. I am not making a direct comparison to Biotin because trial length was different. But rather providing another illustration of absolute and relative risk.

Let’s look at the figures from the TEMSO trial. http://www.nejm.org/doi/full/10.1056/NEJMoa1014656

20.2% experienced disease progression on 14 mg of teriflunomide (N= 358) and 27.3% experienced disease progression in the Placebo group (N=363). The absolute risk reduction with 14mg of Aubagio was 7.1% and the relative risk reduction was 29.8%.

It is always important to keep in mind that absolute risk and relative risk are quite different but keep in mind that MS meds are most often presented in terms of relative risk. I wish they weren’t because it can be confusing.

IMHO, from looking at one year results of teriflunomide it appears that the Biotin trial has every chance of succeeding as well or better than teriflunomide and with far fewer side effects.

BTW, the relative risk reduction on Avonex at two years is about 37% and that in RRMS, not progressive forms. MS meds are helpful but not that great, IMO.

The big news, IMO, was that the Biotin trial was in SPMS and PPMS. That was the real news. Any treatment improving progressive MS deserves special note in my book. Current MS meds do not seem to have much effect, if any, in progressive MS trials, IMO.

I realize people have different opinions about this trial but I have no interest and less time for contention so in the interest of congeniality will not address this issue again. It’s ok to have differing opinions. I will close with a couple quotes and let people form their own opinion about over-hype, under-hype, or no hype. Let the chips fall where they may.

“First time a drug has decreased the rate of disease progression in addition to improving a significant proportion of patients with progressive MS.

“ ….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.”

[teena marie]

This is great. Always interesting to have input. I'm a research nurse and enjoy these discussions. I agree it's the first time there has been something for progressive MS. Also with relatively few side effects. I'm not sure how others feel but I would say don't stop.

Teena Marie

[fightback]

Biotin

After checking with my doctors I started taking Biotin 3 months ago at 5 mg/day. I have been steadily increasing the dosage and I am now at 150 mg/day. It has definitely improved some of my plumbing issues, easier to empty my bladder and eased the constipation as well as decreasing some of the numbness and tingling. Walking has not improved but I am headed back to physical therapy for some remedial walking instruction. No bad side effects so far. My doctors told me that if I ran into any problems with it, it would all be out of my system within a day or two after stopping it. I continue on headed to 300 mg/day which is where the clinical study found the most beneficial effect.

[undisclosEd]

There is a group on Facebook now named;
Biotin for Progressive MS. The group has grown to over 2500 members now and is a great resource for all things related to adding Biotin to your list of MS medications.