MedDay’s New Phase 3 Trial and Belief in Biotin’s Potential to Treat Progressive MS: An Interview with Dr. Frédéric Sedel

MedDay’s New Phase 3 Trial and Belief in Biotin’s Potential to Treat Progressive MS: An Interview with Dr. Frédéric Sedel

A global Phase 3 clinical trial assessing MD1003 — also known as high-dose biotin — for progressive multiple sclerosis (MS) might lead to the approval of one of the first treatments helping select progressive patients to improve.

The trial aims to prove that high-dose biotin can reverse disability in non-active progressive MS. While this has been seen in an earlier Phase 3 trial, the new trial is much larger — ensuring a much greater volume of data will be collected — and, equally important, it may bring the U.S. Food and Drug Administration (FDA) to initiate a review of the treatment’s effectiveness as a first step toward possible approval.

Multiple Sclerosis News Today spoke to Dr. Frédéric Sedel — co-founder and CEO of MedDay Pharmaceuticals, which is developing the treatment — and the man who, by chance, led the team that discovered that biotin in high doses benefits progressive MS patients.

The story of how biotin ended up in a Phase 3 MS trial is, in many ways, a story about Sedel. It is a story of a French researcher who followed the path laid out before him and his colleagues by research findings. It is also, indeed, a story of lucky circumstances — a rarely mentioned but often influential contributor to medical research.

The trial, called SPI2 (NCT02936037), is in its early stages of enrollment — and recruiting across the U.S., Canada and several European countries — but Sedel expresses a clear hope, even a guarded expectation, that outcomes will be good. His optimism is partly based on data from earlier clinical trials, showing that high-dose biotin could reverse disability progression in some patients.

And it is partly based on the fact that thousands of MS patients are already under biotin treatment in France — where the drug was granted early access rights under a special program — in advance of potential European and U.S. regulatory approvals.

The trial

The SPI2 trial — made possible by funding of mainly French investors — aims to recruit 600 patients at 70 sites worldwide. Recruitment is ongoing, and MedDay hopes to be done by the end of the year. (Enrollment information is available here.)

Patients will be randomized to receive either 100 mg of biotin three times a day, or placebo.

The trial will be double-blind, and data will not be available until the patients have been treated for 15 months — which researchers expect to be by mid-2019.

Sedel pointed out that there will be no interim analysis. “An interesting point with biotin is that it doesn’t seem to work in the short term,” he said. “When we start the drug, we start to see an effect after at least nine months of treatment.”

Participants who complete the trial will then be enrolled into a 12-month, open-label extension study, meaning all will be given biotin.

A study for the usually excluded

Unlike the vast majority of MS clinical trials, the Phase 3 SPI2 trial is enrolling only primary and secondary progressive patients without relapses.

The reason for this is that researchers believe that neurodegeneration — and not inflammation — causes disability to accumulate in progressive patients. Progressive patients are, therefore, frequently excluded from clinical trials of drugs aiming to stem disease activity by harnessing inflammation.

In contrast, the pharmaceutical formulation of high-dose biotin — which is a type of vitamin B — has no impact on inflammation, the driving force behind relapses and “active disease.”

“The biotin that we use has no anti-inflammatory effect – so there is no impact on the relapses,” Sedel said.

Including patients with relapses might also make data difficult to interpret, Sedel — who was a practicing neurologist at a leading Paris hospital before starting MedDay — pointed out.

“We don’t want to be polluted by relapses, which may cause unwanted noise in the evaluation. Because if you have relapses then the patient will worsen, not because of the drug but because of their ongoing inflammation,” he said.

To meet these criteria of a “pure neurodegenerative MS population” — as Sedel put it — the trial is recruiting patients who are moderately to severely disabled, scoring 3.5 to 6.5 on the Expanded Disability Status Scale (EDSS).

Disability is, of course, also needed to prove the main point of the trial: that the drug can actually reverse neurodegenerative disease processes, and hence, disability.

The trial will have a narrow focus within the defined patient group. To make it easier to measure improvements, the study will home in on patients with walking difficulties. Measuring improvements in the timed 25-foot walk test is, along with changes in EDSS, its primary outcome measure.

But MS disability comes in many shapes and forms. Will high-dose biotin help patients with other types of disability?

Sedel clearly believes so.

“We are focusing on the population which has gait impairment, to be able to get enough of a homogenous population — and we see an effect on gait impairment, but it doesn’t mean there is no effect on the other functions,” he said. “We don’t think this is only a drug for gait improvement. We have other scales in the trial … [and previous trials] showed that not only gait was improved.”

A twist of fate

How did Sedel discover the potential of biotin in MS? The vitamin is sold over-the-counter as a supplement, but in doses a hundred-fold lower than those used in MS.

To explain, Sedel took us on a brief tour of his earlier career.

“I was a neurologist, and I was – that’s weird – but I was the inventor of this drug. That’s how life goes; it can be strange like that,” Sedel said of his time at Pitié-Salpêtrière Hospital in Paris, France.

There, he studied rare genetic conditions causing inherited metabolic diseases. Many of these conditions involve enzymes needed for normal brain function.

Although these diseases can be caused by abnormalities in a host of different enzymes, they can be treated in similar ways, Sedel explained.

“The nice thing is that you can treat these patients with inborn errors of metabolism by different co-enzymes,” Sedel said. Co-enzymes are factors needed to facilitate the work of enzymes. One of the co-enzymes used was high-dose biotin.

At the time, Sedel discovered a group of patients who shared the common feature of brain damage caused by defective myelin. Sedel believed that their brain abnormality was caused by a common genetic defect. Since the patients became better with biotin treatment, he named the disease biotin-responsive leukodystrophy.

But work to identify the presumed genetic cause proved difficult, Sedel and his team also discovered that one of the patients was, in fact, misdiagnosed. This man most likely had a type of progressive MS that resembled leukodystrophy. And he responded very well to high-dose biotin.

Early studies

While an observation of one patient becoming better after a treatment can be intriguing, it’s a drop in the ocean. So Sedel launched a small pilot trial to see if other progressive MS patients reacted to biotin in a similar way.

Although small, the study’s findings spoke for themselves. Of the 23 enrolled patients, 91.3 percent experienced a lessening in disability.

The development spurred Sedel, together with Dr. Guillaume Brion, to start MedDay in 2011. But it took until 2013 for the two to fully commit to the development of MD1003. “2013 was when myself and Guillaume decided to leave our privileged jobs and go full time in the company.”

The recruitment of sponsors allowed MedDay to launch two additional clinical trials — the MS-SPI (NCT02220933) and MS-NO (NCT02220244) studies. Just as the currently running study, the MS-SPI trial included only progressive patients without relapses.

The MS-NO study, in contrast, also enrolled relapsing patients. The study was intended to examine if biotin could help speed recovery after a relapse in patients with optic neuritis. But unlike the clear effects found in people with progressive disease, researchers did not see treatment impact in this group.

Data from the French MS-SPI trial — published in the Multiple Sclerosis Journal in 2016 — showed another picture. In the pilot study, researchers recorded all types of improvement. This time, the criteria were more strict: patient needed to improve their EDSS score or their performance in the timed 25-foot walk test. Of those receiving MD1003, 12.6 percent did. In the placebo group, that number was 0.

“That’s how we became completely convinced that there was something completely new here, something working on the neurodegeneration. We knew that biotin had no effect on T-cells, B-cells; it had nothing related to inflammation,” Sedel said.

“What we observed in patients was progressive improvement, which was very unusual, as you know — patients with progressive MS, as with other neurodegenerative diseases, are not supposed to really improve.”

The results, he said, seem to be durable throughout the currently running extension trial, which will continue to monitor its patients until biotin becomes approved. “We do not end the trial until we get market approval, because it is very important to get long-term data.”

But as the extension continues, people are dropping out, making analyses of durability difficult. “The data on the population that is still being followed in this trial, which may not be representative of the whole population … it seems that there is a sustained efficacy,” Sedel said, underscoring the need to be cautious in interpretations.

Although Sedel did not mention reasons for people quitting the study, they may be linked to the fact that French patients can now access the drug outside of the trial.

French authorities granted MD1003 a temporary license, known as an ATU, allowing access before the European Medicines Agency (EMA) have its say on marketing authorization. Since MedDay is obliged to keep track of these patients, the program can provide important data supporting the effectivity of the treatment.

“Physicians have treated about 5,000 patients, which is huge. I think it’s very rare to have a drug  … [in an investigative stage with] results in some 5,000 patients,” Sedel said.

MedDay has presented data from the extension phase at earlier scientific conferences, and plans an update for the ECTRIMS meeting in Paris in October. There, the company will also showcase observations in the early access patients.

Regulatory outlooks

In Europe, data from the French MS-SPI trial and the early access program has been accepted by the EMA as sufficient to apply for regulatory approval.

“This data are competent enough to get [considered for] European approval and this is what we are discussing today with the EMA,” Sedel said. A decision, he said, is possible by year’s end.

The FDA, in initial discussions, asked for a study in a U.S. population, which prompted the launch of the SPI2 trial. The global Phase 3 study largely intends to confirm previously acquired findings. But it will also include more measures of MD1003’s safety and efficacy. Researchers will use scans to measure brain changes, follow ambulation remotely, measure ambulation remotely, and, again, evaluate participants’ quality of life.

Comparisons

MedDay has no plans to compare MD1003’s effects to other MS drugs, because such a comparison cannot be done.

“In this non-active progressive population, this is no real comparator — there is no other drug, to my knowledge, today available to treat the patients who are still progressing despite the control of their inflammation. That’s why we cannot use a comparator, we can only use a placebo against our drug,” Sedel said, and took Ocrevus (ocrelizumab) — newly approved for primary progressive MS — as an example.

“It would not make sense to compare biotin with Ocrevus … because Ocrevus is acting on one thing and biotin is working on something else. You are comparing apples with bananas, or whatever you say in English,” he said.

Although authorities have yet to approve MD1003, Sedel  clearly believes in the potential of biotin, and, by extension, in the future of his company. He started the company with just one partner. “Today we are 75, and we will continue to grow,” he said.

If the SPI2 trial is successful, he is sure to be right.

35 comments

  1. Amanda Pickering says:

    I’m interested to join the trial, could you please let me know how I can do this? I have SPMS, and live in South West England. Thank you.

    • Magdalena Kegel says:

      Hi Amanda,
      There is a link in the article to enrollment information for the trial, including contact details.

  2. I have had my wife with MS on 300 mg of Biotin now for over a year and a half, ever since I read the early results of the clinical tests / discovery in France. She is secondary progressive having been diagnosed in 1987. She basically is scooter, walker, cane and wheelchair bound depending on the circumstances.

    SHE AND I ARE COMPLETELY CONVINCED OF THE BENEFITS OF A DAILY DOSE OF 300 MG OF BIOTIN.

    Her improvements are as follows:
    1.) Fatigue has dropped dramatically.
    2.) Mental faculties have improved.
    3.) Mental well being has improved dramatically.
    4.) She previously fractured her right hip twice and therefore it is difficult to measure mobility changes related to the Biotin.
    5.) Energy levels have dramatically improved.
    6.) Total washout days have dropped to zero.

    She and I would highly recommend mega doses of Biotin for MS as set out in this article. If pharmaceutical grade Biotin was available here in the U.S., we would use that Biotin.

    Good luck to all!

    • Yvonne childs says:

      Thank you for this information, I will try this also.
      I hope you continue to improve. Best wishes, Yvonne

    • neil bealham says:

      Entirely agree! my wife’s been taking 300 mg biotin for over 2 years , fatigue days greatly reducing, mental faculties improved. She is wheelchair bound but her general condition has not got worse in the last two years! That to me is great!!!!!

      Good luck to All

    • Larry Radanovich says:

      Yes it is, my wife is is very similar to yours,diagnosed in 1994 has gone from cane to walker to el chair. From avonex to beta sermon and the last few years copaxone after a visit to UCLA arranged by her neurologist, last year I got a call from a friend who is a retired pharmacist who had just read about the French study and I read the study but I could not find the right formula, I could not imagine 30 pills. a day but finally found a 100mg formulary made by ACE Rx sp ecialty pharmacy through Amazon http://www.acerxpharmacy.com ph# 732 952 2244. Started her on regimen last May with results similar to yours

  3. Frank DiPasquale says:

    I don’t like it when studies say that there was improvement and not somehow quantify it, because you don’t know where the improvement occurred and how much improvement there was? Can anyone relay the edss score mobility improvement with biotin?

    • Kevin Ryan says:

      Cutting it short. MS 3 years ago. on biotin powder 300 per day for 2 years. My eyes focus better I play pool and I see the difference.I hope helpful.

  4. Dorothy Leblanc says:

    I am very interested in this drug. I am a SPMS patient who is seventy years old. Would I be a candidate for the drug?

  5. Steve Perry says:

    You can buy “High-Potency Biotin D-Biotin” 100mg, NOT 100mcg, from ACE RX Specialty Pharmacy, for approx $75. for 180 100mg Casules – 3 x 1 100mg daily. You don’t need an RX. According to most studies I’ve read it takes 9-18 months for results to be seen, but it’s said to be approx 90% effective.

    They also compound LDN and 4-AP (Generic Ampyra without time release). This is the most accredited compounding pharmacy I have been able to find in the US.

    Highdosebiotin.net
    732-952-2244 – ask for Chris tell him Mr Perry sent you

  6. Johanna Jager says:

    I have secondary progressive MS. Symptons since late 1980’s no definite diagnosis. Now unable to walk and mostly in wheelchair or bed. Seems to be stable and able to use upperbody. Never had fatigue or pain and used to exercise a lot. I wonder if I would be a candidate.

  7. Phil Longford says:

    This is interesting. While Ocrebus is aimed at halting the progression, high dose biotin actually dares to use the work, improvement! Ok, may take some time to start working, but better than nothing.

    • Tim Bossie says:

      That’s true Phil. It looks like Biotin may be something that many people will benefit from without harmful side effects.

    • Tom devine says:

      Tom Devine, diagnosed with ppms in 2015 difficulty walking wondering if I could be part of study currently getting infusions of rotuxin every six months not getting relief in walking or chronic leg pain. My age is 47 upper body is currently doing ok most of the time. Last MRI showed no new lesions that was in 2016 aug. I did not get any relief from other Meds my nero had me try.

    • Magdalena Kegel says:

      Hi Rowena,

      There is a link in the article to enrollment information for the trial. The link leads to a page that includes contact details. Good luck with the enrollment!

    • Magdalena Kegel says:

      Hi Rashmi,

      There is a link in the article to enrollment information for the trial. The link leads to a page that includes contact details. Good luck with the enrollment.

  8. Ursula says:

    I would encourage anyone who is considering taking high-dose Biotin to check this with their doctor first. At present I am taking Tecfidera & also have Hypothyroidism. After taking Biotin I developed dangerously high thyroid levels & became quite unwell. I still am recovering and taking a reduced dosage of levothyroxine nearly 1 year later after stopping Biotin as per doctor.

    • Tim Bossie says:

      That is absoultely right Ursula. Everyone should consult with their doctors before taking any over the counter medicine and be monitored as well.

    • neil bealham says:

      Hi ,
      My wife after taking biotin got bad thyroid results from pathology checks, it turned out the standard thyroid pathology test gives faulty thyroid checks if taking Biotin the high levels affect the chemicals used in the standard test and gives false thyroid results. After ultra sound on thyroid, doctor sent pathology to a different pathlogy lab which uses different method to check thyroid levels all found normal. This all took a lot of time Jo my wife stopped taking Biotin for two weeks Thyroid levels checked out fine. Went back on Biotin Thyroid levels bad. Had ultrasound on thyroid they did not find anything of concern.Another pathology test while Jo was taking Biotin to lab that used a different test from another pathology lab thyroid results fine!!I

      Read this Article (google search Biotin Thyroid)

      In What Way Does Biotin Alter Thyroid Testing?
      Recently, children with inherited metabolic diseases receiving high doses of biotin were found to have elevated levels of thyroid hormones and thyroid antibodies. These results resembled Graves’ disease, an autoimmune condition in which thyroid antibodies stimulate the thyroid gland to produce too much thyroid hormone, resulting in hyperthyroidism. However, the children did not have the typical symptoms of hyperthyroidism: they did not have a fast heart rate, restlessness, or show developmental delays. Further analyses revealed that biotin interferes with the most commonly used thyroid hormone test systems, mimicking lab results seen in Graves’disease.

      Additional analyses have shown that biotin’s interference with lab tests can also result in a low thyroid hormone level reading, depending on which lab testing system is being used. After stopping biotin, interference with laboratory tests has been reported to disappear within eight hours, although other researchers have reported it might take 24 to 48 hours for some of the more typical tests that might be ordered, and up to seven days for some antibody tests.

      Hope this helps

      You obviously have a problem with your thyroid, but be aware that if you take Biotin it will give you false results for thyroid function.

      Hope you get well

  9. louise says:

    my thyroid levels were completely abnormal also when I was on biotin .After going of it for 3-4 months they were completely normal again.We discovered then that this phenomena is well documented on the net GOOGLE IT

  10. Christine says:

    I was diagnosed in Oct 1999. I was using a walker/wheel chair before my doctor suggested I try 300 mg of biotin a day October 2015. To date my energy has increased, I am walking unassisted, my arm strenght has improved. It took about six months to begin to notice improvement. I feel like I have reversed and have my life back. I still get fatigued. But nothing like pre Biotin.

  11. Frank Weber says:

    Ich bin 74 Jahre und habe seit ca. 40 Jahren MS, benötige seit 6 Jahren Rollstuhl. Ich nehme schon 18 Monate Biotin (300mg pro Tag)habe keine Krämpfe mehr und kann wieder klar sehen. Inzwischen ist auch meine Neurologin überzeugt!eber

    • Petra says:

      Guten Abend,

      Ich schreibe aus Kroatien.
      Ich habe MS schon viele Jahre.Ich bin 41 Jahre alt.
      Ich kann kaum laufen nur im Haus aber sehr schlecht.
      Bitte Info um Biotin.Kann das bei laufen helfen ds ich slber kaufen kann und bei Sapaztam Krampfe bitte? Ich freue mich auf Ihre Antwort.Gruss,Petra

    • Steinert says:

      Hallo H. Weber,
      Meine MS begann 1971, ich bin gleich alt wie Sie und benutze seit 17 Jahren einen Rollstuhl. Mich interessiert: Haben Sie eine seriöse Quelle für Biotin? Welche?
      Viele Grüße, Ulrich Steinert

  12. Sam Menter says:

    Useful and informative , I am planning to buy biotin for my sister. She has been recently diagnosed with Primary Progressive MS

  13. I am in BC, Canada, I’ve been taking biotin 100 mg 3 x a day for a year now, about to start my second year of it. I am SPMS. I tend to find it expensive though. I pay approx $312.99 for one month. Does the company offer any financial relief at all?

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