The biotin trial results are out

Biotin is an emerging therapy for the treatment of secondary progressive MS.
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Re: Paraphrasing

Post by 1eye » Fri May 01, 2015 9:28 am

I have written a quick description of the talk. No direct quotes. Apologies to those who read this when it was only partially submitted.
I have also fixed some things due to Sharon's comments, below...

This is all paraphrasing and editorial: there are no direct quotations.

The usual suspects have managed to taint only one of the MedDay group (Dr. Tourbah). Either a spy in their midst or a counter-spy maybe. Actually it's the top name on the paper, so maybe he's just being completely transparent, and collecting fees. He was the one speaking and answering questions.

BTW it's quicker to download it if you can, from either place.

They had already done one trial before this one, so they may have ongoing data, because they probably kept those patients on the drug. Same with this study and subsequent ones, which they will report at a future meeting. We will see therefore, if the improvements continue.

The primary purpose was to test effects on the Expanded Disability Scale (EDSS), and timed walking speed measurements.

He said MS might be caused by virtual hypoxia: a mismatch between energy demand and energy production, caused by the inability of mitochondria to consume oxygen. Not clear if this is limited to the brain; I think not, eventually, but maybe the divide is between brain/spine and rest of nervous system. That would mean it follows the CSF (Cerebro-Spinal Fluid) from brain to spine (it does, all the way to mice, in other experiments).

They weren't taking DMDs, introduced withing 3 years, though they could if introduced less recently, or Fampridine (improves walking speed in relapsing-remitting patients), if introduced within 3 months. The fact that these were not RR patients may mean it works for them too, indicating they are treating the same disease (relapsing and progressive diseases share the same cause).

154 patients, 1/3 placebo, had 2 adverse events in each group, with 1 suicide, not related.

13 treated patients improved by trial standards, and none in placebo group.

Twice as many patients improved in EDSS as in walking. This is because EDSS is defined more by ability to walk at all, than by speed of walking.

Number of improved patients was statistically significant. Looking at the EDSS graph, it looked like progression was halted. This means something to me because I have always said, halt the progression and I'll do the rest.

This is borne out by slight improvement overall in average EDSS.

Improvements in EDSS at 3 months continued until 9 months, with a deviation at 3 from placebo, of 67%, illustrating the end of placebo effect. Continuation of the improvement lasted for the full 9 months.

When combined with the results of the other study, the results on EDSS are similar.

For timed walking, on average the treated patients were 6 seconds faster than the placebo group. This might not seem like much, and it doesn't get me out of my walker, but I can probably do that myself once I stop backsliding. The trend looks like I will stop backsliding.

Twice as many placebo people as the treated ones, had adverse events, but biotin appears to change the results of antibody tests, so the tests themselves will have to be reconsidered for people on Biotin.

There were questions both from audience and phone calls.

The question session contained:

Will you get marketing approval?
We have to do two more studies, and then European approval, then (possibly) one more, for the US, depending on whether they like what we have done by the end of the year.

Note re Sharon's update: Are they waiting till 2017 to give the other DMD vendors a chance to make some more money before they go to market?

Any other improvements?
We are testing for them. Some look like they do improve.

Cognition?
Yes we have seen this, seems significant. Some others look good too.

Do you plan to look at relapsing-remitting? If not,why not?
Not specifically, but we do have some R-R patients in our Optic Neuritis study who have permanent ON problems, so if they improve, we will know it does not matter whether they have remissions of other symptoms or not. So we will test both. Biotin does not seem to care. It is a tough requirement, but we are hopeful.

Does it rebuild myelin, or stop progression?
Both. We think it modifies the primary disease. We aren't sure if it does both, repair myelin, and decrease virtual hypoxia, but we think it will.

Should people start buying biotin?
:-)
Don't know what people will do, but reasons they shouldn't are: a) it might be toxic in those doses, especially for rabbits and pregnant women, and b) because it also seems to dramatically change the results of medical tests including thyroid and pregnancy tests. Plus medical grade biotin at these doses is more of a guarantee of purity, and even whether it is biotin at all.

Can you combine it with other DMDs?
Yes, many subjects did, with no problems.

Is your research platform able to look at CSF?
No; we couldn't ask them to have spinal taps, but research will continue.

Can you predict who will benefit?
No.
Last edited by 1eye on Fri May 01, 2015 2:14 pm, edited 5 times in total.
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Re: The biotin trial results are out

Post by Sharon » Fri May 01, 2015 11:34 am

Nice summary 1 Eye...just a few corrections and additions.

Tourbah is the Principal Investigator

The first pilot study:
MD1003’s proof of concept has been obtained in a pilot open label study1 involving 23 subjects with primary and secondary progressive MS. Results were positive with up to 90% of subjects exhibiting some clinical improvement over time.
http://www.medday-pharma.com/news-and-e ... sclerosis/

The CEO of MedDay confirmed today that the drug will not be available before 2017 (specific date unavailable because of time limitations with the approval process)

1 eye said
Should people start buying myelin
I think you meant Biotin. :-) In my opinion, the OTC Biotin should not be considered. In order to get the high dosage you are taking a quantity of tablets and we all know that OTC supplements are not all the same, plus you are high dosing yourself with the fillers used in the tablets. If someone is planning on trying the Biotin, use a reliable compounding pharmacy (send them the research)...and, of course you will need a script from a doctor to get the order. The MedDay drug has no secret ingredients in it -- it is a high dose of a pharmaceutical grade of Biotin.

i eye said
Is your research platform able to look at CSF?
This was a question I asked. I was interested to know if they used their research platform in this study. This is from the MedDay website
The SPECMET metabolomics platform screens cerebrospinal fluid (CSF) from patients with CNS disorders to identify metabolic pathways that are disrupted. The goal of this approach is to identify approved or shelved compounds that are known to target the aberrant pathway.
The answer was "no" it was not used because the patients would have had to undergo an invasive spinal tap.
IMHO - The research platform is an interesting concept and hopefully will be successful in the long term.

More to learn.....MedDay will be presenting at the EAN conference June 20, 2015. Abstract will be available on the EAN website June 13, 2015. Presentation is during one of the Oral Sessions, so this will be another opportunity for a detailed report.

Sharon

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Re: The biotin trial results are out

Post by 1eye » Fri May 01, 2015 1:56 pm

As I said I did all the compounding myself, and the source was at least North American, so it might be pure.
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Re: The biotin trial results are out

Post by 1eye » Sun May 03, 2015 8:47 am

BTW Suzanne (She Who Must Be Obeyed) points out that MedDay is an English/French pun (M'aider).
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Re: The biotin trial results are out

Post by lyndacarol » Sun May 03, 2015 8:59 am

1eye wrote:BTW Suzanne (She Who Must Be Obeyed) points out that MedDay is an English/French pun (M'aider).
Thanks to Suzanne for pointing this out! How clever! This never occurred to me.

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Re: The biotin trial results are out

Post by eric593 » Sun May 03, 2015 9:41 am

lyndacarol wrote:
1eye wrote:BTW Suzanne (She Who Must Be Obeyed) points out that MedDay is an English/French pun (M'aider).
Thanks to Suzanne for pointing this out! How clever! This never occurred to me.
I don't understand????

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Re: The biotin trial results are out

Post by jimmylegs » Sun May 03, 2015 9:47 am

if you say medday fast it would sound the same as m'aidez or the perhaps more familiar 'mayday'
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!

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Re: The biotin trial results are out

Post by 1eye » Sun May 03, 2015 10:49 am

jimmylegs wrote:if you say medday fast it would sound the same as m'aidez or the perhaps more familiar 'mayday'
That's because http://tinyurl.com/okagcaz
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Re: The biotin trial results are out

Post by jimmylegs » Sun May 03, 2015 11:25 am

yes, shockingly, it's not a coincidence ;)
take control of your own health
pursue optimal self care at least as actively as a diagnosis
ask for referrals to preventive health care specialists eg dietitians
don't let suboptimal self care muddy any underlying diagnostic picture!

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Re: The biotin trial results are out

Post by 1eye » Sun May 03, 2015 3:37 pm

From http://www.thisisms.com/forum/chronic-c ... ml#p234140
and http://www.nutri-facts.org/eng/vitamins ... -a-glance/
Vitamin B7 deficiency is extremely rare, which is probably due to the fact that biotin is synthesized by beneficial bacteria in the human digestive tract.



Groups at risk of biotin deficiency include patients maintained on total intravenous nutrition, hemodialysis patients, diabetes mellitus patients, and patients with an impaired uptake of vitamins from food. In addition, pregnancy may be associated with marginal biotin deficiency.



Symptoms include hair loss, dry scaly skin, cracking in the corners of the mouth, swollen and painful tongue, dry eyes, loss of appetite, fatigue, insomnia, and depression.
Could it be that modern antibiotics are killing off the same gut bacteria that provide natural B7 and that modern MS is somehow related to a vitamin B7 deficiency caused by excessive antibiotic use?

I suffered a bad bout of Osteomyelitis when I was 12 (interestingly, same leg that's worst now). It had only been recently that they had been treating it with antibiotics. My father had it and had to have a finger-bone operation, after which he could no longer fret a violin. In my case, they used a very long course of antibiotics. During that same time I was also on IV feeding for about 2 weeks.

What about diabetes, which my Dad had, and my brother has now (same brother who had the bone marrow transplant

Watch out for anonymous non-medical testimonials:

From a bulk biotin vendor site:
On 4/26/2015 william said...

Growing evidence from recent studies in France support the role of biotin in ameliorating the course of demyelinating neurological disorders such as ms, cidp, and idiopathic neuropathy.
I have begun a 12 month trial using the pure form of biotin at 300mg a day..at 9 months and 12 months I will report any changes in function.
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Re: The biotin trial results are out

Post by Jimpsull » Mon May 04, 2015 1:27 am

I like the comment about biotin not caring whether its RRMS or SPMS. Hopefully insurance companies won't be able to insist we take one or the other (DMD or MD1003).

It is unfortunate that we feel the need to classify our MS as either or when in all cases it is most likely both. I have seen SPMS patients have exacerbations (relapses) and I have been progressing as an RRMS patient. What separates a bad week from a relapse? Most likely not mechanism but only scale. So if your relapses are too small to be seen by your Nuero you must be SPMS?

I don't think so, but I'm sure the insurance companies do. If copaxone is doing its job (lowering relapse rate) and the patient is still progressing - does that mean they no longer need copaxone? That's a load of hogwash - but the insurance companies will surely note that glatrimar isn't FDA approved for SPMS. Ok, no worries, this patient will soon be able to take biotin (MD1003). Until they have a relapse and realize that SPMS and RRMS are not either or but both and.

Which is why I am taking copaxone AND d-biotin (10 mg 20x daily with sunflower seeds)

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Re: The biotin trial results are out

Post by 1eye » Mon May 04, 2015 12:07 pm

More paraphrasing, this time from the folks at the AUTOIMMUNE DIGEST. I promise not to repeat this info...

My only comment is that they are definitely leaving no posteriors uncovered
Vitamin Promising in Progressive Multiple Sclerosis
Washington, DC — A regimen of high doses of biotin, a water-soluble B vitamin, appears to be effective in patients with primary or secondary progressive multiple sclerosis (MS), according to emerging research.

A new phase 3 study of the investigational drug MD1003 (MedDay Pharmaceuticals), a highly concentrated pharmaceutical-grade biotin, found that patients with progressive MS taking the drug had significant improvement at 9 months, which was confirmed at 12 months, compared with those taking placebo.

"We are encouraged that the primary endpoint was met despite the very high bar for treatment response," said the study's principal investigator, Professor Ayman Tourbah, of CHU de Reims, Neurology, France, in a press release.

The results, he said, suggest that MD1003 "could be an important and efficacious treatment for primary and secondary progressive multiple sclerosis."

Currently, there are no effective therapies for progressive MS.

The results were presented at the Clinical Trials Plenary Session during the American Academy of Neurology (AAN) 67th Annual Meeting and again during a subsequent webcast.

Two Mechanisms

Biotin is a coenzyme for carboxylases, which are enzymes critical in energy metabolism and production of fatty acids. It targets two mechanisms that might be involved in progressive MS: promoting myelination and increasing energy production.

It's hypothesized that biotin may help to slow, stop, or even reverse the progression of disability associated with demyelination.
In his presentation, Dr Tourbah referred to a small uncontrolled "proof of concept" study of 23 patients with progressive MS who were treated with a mean of 300 mg of biotin per day for about 9 months. In this study, 22% of patients had a significant clinical improvement on the Expanded Disability Status Scale (EDSS).

The new study included 154 patients aged 18 to 75 years (mean age, about 51 years) with primary or secondary progressive MS and an EDSS score of 4.5 to 7. During the previous 2 years, they must have had a progression on the EDSS of at least 1 point if their baseline EDSS score was 4.5 to 5.5, and of 0.5 point if their baseline EDSS score was 6 to 7.

Patients were randomly assigned to placebo (n = 51) or to oral MD1003 (n = 103), which is tasteless and colorless. The mean dose of the drug was 300 mg/day. About 41% of the treatment group and 55% of the placebo group were also taking fampridine, a drug used to manage MS symptoms.

Patients were followed for a mean of 9 months and up to 36 months. Twelve patients in the treatment group and eight patients in the placebo group discontinued the study but were included in the intention-to-treat (ITT) analysis.

Main Outcome
The main outcome was improvement at 9 months, and confirmed at 12 months, using either a change in EDSS score of at least 1 point (if baseline EDSS was 4.5 to 5.5) and 0.5 point (if baseline EDSS was 6 to 7) or a decrease in timed 25-foot walk (TW25) of 20% compared to baseline.

In the ITT population, 12.62% of the MD1003 group and 0.0% of the placebo group met this criteria (P = .0051). In the per protocol population, 14.9% of the MD1003 and 0.0% of the placebo group met the primary endpoint (P = .0093).

Interestingly, said Dr Tourbah, twice as many patients met the primary endpoint with the EDSS (76.9%) than with the TW25 (38.5%).
The results were supported by secondary analyses that showed evidence of a decrease in the risk for disease progression. In the treatment group, there was a mean EDSS decrease of 0.03 at month 12, compared with a mean increase of 0.13 in the placebo group (P = .014).

"Overall, these results show patients in the MD1003 group not only did not progress but even slightly improved within 12 months," commented Dr Tourbah.

He also reported that in the MD1003 group, only 4.21% of patients exhibited EDSS progression at month 9, confirmed at 12 months, compared with 13.64% in the placebo group (P = .07). This represents a 67% difference in risk for progression in the active group. (The study was not prospectively powered to reach significance for this secondary endpoint.)

No characteristics appeared to differ between the patients taking the drug who had disease progression and those who didn't experience disease progression, said Dr Tourbah.

Similar Safety Profile
Infections and infestations were documented in 34.0% of the treatment and 33.3% of the placebo group and nervous system disorders were seen in 28.2% of the treatment and 39.2% of the placebo group.

The placebo group had twice as many MS relapses (7.8% vs 3.9%) and more gastrointestinal disorders (23.5% vs 12.6%) and musculoskeletal and connective tissue disorders (19.6% vs 12.6%) as did the treatment group.

The two groups had about the same rate of psychiatric disorders, at just under 10%. There was one suicide in the treatment group and none in the placebo group.

No one in the placebo group but five patients in the treatment group had "apparent hyperthyroidism," or low thyroid-stimulating hormone. Dr Tourbah explained that a high biotin plasma concentration interferes with immunoassays using biotinylated antibodies.
"This requires a specific management plan," linked to a prescription for this drug, to ensure that patients and physicians are aware of this problem, he said.

A false laboratory test result could create problems clinically for patients getting pregnancy tests, or various screening tests.
This adverse event is "a main issue" with the study, commented Lily Jung Henson, MD, a neurologist specializing in MS at Swedish Medical Center, Seattle, Washington. But despite this concern, the drug was reasonably well tolerated, "which is critical," she said when asked her view of the new study.

The fact that the drug may affect axonal metabolism "is exciting" said Dr Jung Henson. She also noted that the advisory board involved with the study included several well-known experts in the field.

Supplement Form
Although biotin is found in some foods, including peanuts, liver, and certain green leafy vegetables, no dietary source is very high in this vitamin. Biotin is also available in supplement form. The usual daily dose is 30 to 100 micrograms.

During the webcast, Frédéric Sedel, MD, chief executive officer of MedDay, warned against MS patients with severe disease rushing off to the health food store or pharmacy to buy biotin. For one thing, it's potentially teratogenic.

"There should be a warning here that pregnant women or those who are planning to become pregnant should not take this drug or very high doses of this vitamin," he said.

As well, unlike the drug used in the study, biotin found on the shelf may be low grade and perhaps not even be biotin. In some cases, said Dr Sedel, patients get vitamin E when they think they're buying biotin.

MedDay will release further results of this phase 3 study, including data on quality of life, fatigue, and other outcomes, at the upcoming European Academy of Neurology meeting in Berlin, Germany.

The company is carrying out another phase 3 study of biotin in patients with MS — including those with relapsing/remitting as well as those with progressive disease — who have vision loss from chronic optic neuritis. After release of those results later this year, the company plans to meet with the US Food and Drug Administration (FDA) to discuss a possible drug approval plan, said Dr Sedel.

There are no FDA-approved treatments for progressive MS, except for mitoxantrone approved for secondary progressive MS, Dr Jung Henson said. That agent carries a very significant risk of heart damage and leukemia, she noted.

"I don't think anyone uses it anymore," she said. "Obviously this new drug is a needed therapy option."

The study was sponsored by MedDay Pharmaceuticals. In the last year, Dr Tourbah has received consulting and lecturing fees, travel grants, and research support from MedDay, Biogen Idec, Sanofi-Genzyme, Novartis, Merck Serono, Teva Pharma, and Roche. Dr Jung Henson has no conflicts with respect to MedDay. She receives research funding from Novartis, Genzyme, Biogen, and Opexa and speaks for Novartis, Biogen, Genzyme, Serono, Teva, and Pfizer. She sits on the board of managers for Fast Forward, which is part of the National Multiple Sclerosis Society.

American Academy of Neurology (AAN) 67th Annual Meeting. Clinical Trials Plenary Session. Presented April 24, 2015.
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Re: The biotin trial results are out

Post by Simvic » Tue May 05, 2015 5:59 pm

Biotin Suggestion - we can undertake a clinical trial with minimal cost, time and great impact

For many PPMSers, the Biotin results released in April/15 have given hope - unfortunately,with clinical data confirmation, regulator approvals and available regulatory approved supply, Biotin does not appear to be happening in the near future - things take time - it sounds like it will be at least 2016-2017

As a result, many PPMSer, who don't have time to wait, are beginning to self dose on over the counter and/ or internet available Biotin - this all has challenges as we know ie bioactivity, fillers, etc

I suggest that Biotin be released now to a very interested PPMS population in a more controlled method with clinical oversight

The challenge is how do we do this quickly, safely and at minimal expense and yet meet the needs of so many PPMSers that have no treatment options?

I suggest tagging on to an existing PPMS clinical trial with existing screened PPMS for eligibility in a placebo-control double blinded study that has already collected extensive biometric (MRI, blood, urine, sight, mobility, 25WT, 9Peg, math)

This way the study population is already willing and available globally and the infrastructure of MS centers, hospitals, doctors and labs is already established

Right now Roche's Ocrelizumab trial - a global trial involving over 660 PPMS for the last 3 years which screened patients + collected biometrics, in a double blind placebo control trial - is winding up in Sept/15 with some sites already finished - data analysis is to be done in the fall of 2015 and open label, if significant, in 2016

I suggest that Roche, MedDay, the Progressive Alliance and the NIH work together and try Biotin as an intervention 'add on' to the Roche-Ocrelizumab study - the study population exists and is ready to go, the infra structure of clinics, clinic visits, physicians, trial co-ordinators, biometric sampling and bioemetric analysis are all in place - the patient data for the last 3 years also exists which can be compared against the Biotin intervention - even is Roche will not turn over the data, the patient population and intrastucture exists

Lets use what we have and get goiing

I'm cross referencing this post to Bart's Blog

Thanks

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Re: The biotin trial results are out

Post by Jimpsull » Tue May 05, 2015 11:09 pm

Those with open minded pcp can probably get a script filled for d-biotin at a compounding pharmacy. Have them write it for nerve damage or balance or for some symptom. If they write it for ms it may expose the pharmacy to patent infringement charges.

One reason I prefer good otc d-biotin is because it avoids the patent issue.

http://enhancedbiotintrial.blogspot.com ... t.html?m=1

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Re: The biotin trial results are out

Post by 1eye » Wed May 06, 2015 9:11 am

even is Roche will not turn over the data, the patient population and intrastucture exists
If the NIH is involved, I think the data is automatically public. I hope we have passed the days when vendors kept data like this a secret. If there are adverse events, that is even more of a reason for publication, if the stuff is available OTC. Beware of vendors who say they have found a reason for something that they don't own not to be used: that is just as much a conflict of interest as someone saying a treatment they do happen to own should be used. Let the patients decide, within reason, especially if they are the payers.

I just can't see a business case for Roche getting involved. Maybe if they were very altruistic, and maybe if MedDay were offering a piece of the action, but otherwise, why would they?
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