Friday, 24 April 2015

MD1003 High Dose Biotin Results

The MS-SPI study with MD1003 was a randomized 2:1, double-blinded, placebo-controlled study conducted in 16 MS reference centres in France. Treatment duration was one year.

The patient population was defined as patients suffering from primary progressive Multiple Sclerosis (PPMS) or secondary progressive Multiple Sclerosis (SPMS) with EDSS progression in the two years prior to inclusion and with EDSS ranging from 4.5 to 7. Patients excluded from the study included those with disease modifying therapy (DMT) introduced in the 3 months prior to inclusion, patients with fampridine introduced in the month prior to inclusion, or patients with evidence of relapse or Gadolinium-MRI activity within the past year.

Patient enrolment commenced in October 2013 and was completed in January 2014 with 166 patients screened and 154 patients randomized (103 in the MD1003 arm and 51 in the placebo arm). There were no statistically significant differences in the characteristics of the patients in the two patient groups.

There were 12 treatment discontinuations in the MD1003 arm and 8 in the placebo arm. All analyses being performed according to the intent to treat (ITT) principle, all randomized patients were analysed according to the treatment arm they were assigned to.

The primary endpoint of the study was defined as the proportion of patients who improved at 9 months (M9), with a confirmation of the improvement 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 primary endpoint was met (p=0.0051, Fisher’s exact test) in the intent to treat population with 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.

The primary endpoint was supported by secondary analyses showing evidence for a decrease in the risk of disease progression. The mean change of EDSS between M0 and M12 decreased in the MD1003 group (-0.03) compared to progression in the placebo group (+0.13, p=0.015). In the MD1003 arm, only 4% of patients treated with MD1003 exhibited EDSS progression at M9 confirmed at M12 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. One patient died from suicide in the active arm, however this event was not considered as related to the drug


CoI. None. However be warned this data is from the company website and not peer-reviewed.
ProfG was there and can give you his thoughts

37 comments:

  1. what's your take on the results?
    It's not as good as they championed really is it

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  2. Can you give us your thoughts on these results? Those of us in the MS community have so many questions!

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  3. On balance, isn't this a positive result? 67% of people in study had disease progression halted as of month 12 - a big deal. Granted it would have been nicer if more than 12% improved. However, until today, I have yet to see a study where there was improvement to the EDSS. As progressive MS has no approved treatments, this study is a big step in the right direction. Perhaps improvement takes more time.

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    1. I think the numbers are saying most people didn't progress noticeably in the short time frame used in this study. But some did. And if you compare the numbers of people who progressed, there were a lot more in the placebo group. In fact, 67% more. That said, I still think it's a big deal. In previous studies, they show all of us progress--even those of us with RRMS. I wonder if biotin would be a good idea for all of us to take alongside our vitamin D.

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    2. It is not 67% of people the difference was 4% worsening in drug verses 13% on placebo showin worsening

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    3. So isn't it promising that only 4% of biotin had progression whereas 13% of placebo did? Isn't that statistically significant? Dammit, I hate having to defend crap results!

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  4. It seems to me that biotin helps to slow progression (by adding extra energy to cells?) but there is hardly any significant improvement hence probably little remyelination:

    so biotin is okay as neuroprotectant but not the magic bullet for restoring lost myelin - am I right?

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  5. I have asked about this on the forum before - whether the degree to which an individual's nerves are "coated" in scar tissue could result in a "ceiling" of benefit from a remyelination agent. So perhaps it would be important to start taking biotin early on. And perhaps it does take a long, long time to work. PPMS took many years to start causing me really serious issues. I am wondering why people with progressive MS benefit from biotin: Is it the lack of ability to absorb it from a normal diet? Biotin is often bound to a protein in foods, I understand. /NS

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  6. Wow, this is the best yet in progressive MS!

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  7. I would like more details. Was there any difference between those at lower EDSS levels versus higher levels. What about MRI evidence ? The improvements could continue over time / after all the damage took years to appear it os not going to magically go away in only 12 months.

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    1. we will have to wait until the data is actually pulished

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  8. IF IT MAKES HALF IT SAYS FOR ME IT´S OK!... THE ONLY QUESTION IS WHEN IT WILL BE AVAILABLE MAN?

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  9. Very welcome news; not yet replicated independently but i'm convinced. I have always suspected that 'mitochrondrial insufficiency' was implicated in ms, if the underlying theory holds then this treatment should relieve spasticity and fatigue in all MSers?

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  10. Huuuummm ... Well if I understand the high doses of Biotin could halt disease progression (interesting if this neuroprotective effect is confirmed, could be used together with the DMT's including for RRMS, right?) And that's something (67% is an "interesting number"). Would have more a neuroprotective effect, right? ... Now what to say regarding the MRI lesions and remyelination?

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    1. It doesn't sound like neuroprotection but symptom control or remyelination

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    2. What do you make of this as neuropototection

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952353/

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    3. Ps I have been in contact with the company and they believe it to slow progression and improve disability

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    4. Anon 4.07. A study on testosterone so not much use for females...if ProfG doesn't respond I will
      Anon 4.19. Based on what ProfG said they would say neuroprotective over symptom control because of price

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    5. Hi Barts blog
      I know that it's no use for women but we have heard for years how men have it worse than women with Ms and I'm sure that disregarding a possible treatment for men because it's not applicable for women would be met with distain

      What are your thoughts on the study? Would surely link the age degeneration thing

      And if you can slow atrophy to normal levels then wouldn't thhat slow disability?

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    6. 1. Its i Prof G in box to discuss
      2. Yes i agreed

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    7. At the least its got to be worth having a blood test and taking the treatment if needed? Especially if it can slow atrophy which is what you guy's keep saying contributes to disability
      It's also seen in spinal injuries that people have lower testosterone ?

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    8. Is is agreed on the slowing of disability?
      Also is it grey or white matter attacked in ppms?

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    9. Any answer prof G?

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    10. Re; "Testosterone trial for men."

      The preliminary data needs to be firmed up; is low testosterone levels a risk factor for developing MS and/or is it a potential disease-modifying therapy. I think data is emerging to support the hypothesis that low testosterone levels may be a risk factor for developing MS in both sexes. I agree testosterone may also have disease-modifying effects, but the side effect profile of long term testosterone therapy are worrying; higher incidence of cancers, in particular prostate, and cardiovascular disease. With regard to the latter there is currently a class action lawsuit against several Pharma companies in the US for promoting testosterone supplementation therapy for low testosterone levels in men,

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  11. Awesome the best thing in progressive ms by a long shot

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  12. I'm whelmed. 12.7% isn't exactly hang from the rafters news but the 67% stop sounds like a good enough reason to buy a bottle and monkey around with it.

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    1. Sorry to burst the bubble but it is not 67% stop, it was 13% placebo verses 4% drug with worsening

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    2. Think I'm lost in translation: "I'm whelmed" is American slang for 'not at all enthused'/the opposite of being overwhelmed. Those are shitty numbers, even more so with the placebo. Two countries, language, etc.Have some cheese, good mousedoc.

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    3. I got the whelmed but many people took the 67% as the big news, so the moral here is we have to wait until we see the data before we get too excited about news.

      The biotin has had a positive effect on some people work out why and find out if benefit can had earier in MS.

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    4. I'll still try it out albei in lower dosage because it makes sense to me to prop up energy levels in nerve cells that had been attacked and hence need more power than healthy ones to transmit messages.

      Btw, a few years back right after my second attack I started to take enzymes (different than biotin) for a while waiting to start a DMT.

      I felt a noticeable improvement of my symptoms but could not explain why - until now, when it were the enzymes most likely interfering with the energy metabolism, so that is interesting.

      I wouldn't write biotin off at this stage.

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  13. It's really not that great at all
    And that's disappointing
    The only thing it may do is speed others up as they would hate for one company to monopolise the market
    I'm gutted

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  14. So what do we make of this ?..............http://www.sciencedirect.com/science/article/pii/S2211034815000061

    Regards as always

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    1. This was the phase II data blogged in March and hence the suggestion that the drug was a symptomatic or remyelination drug. this data is now superceded by the current study;

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  15. I think that 0% improvement in the placebo group is a sure sign of unblinding or bogus results. It's so easy to go from an EDSS 6.0 to 5.0 based on fluctuations in weather/sleep/diet/exercise/random chance. I think underperformance of the placebo group arm is a sure sign of implausibility

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  16. God willing we will have good results for the second biotin phase 3 trial and then the doubters will be converted. Wait and see ;)

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  17. 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 wihich 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 This Is MS

    Thanks

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