Biotin (MD1003) Fails to Prevent Disability Progression in Progressive MS Patients, Trial Shows

Note: This article was originally published on www.multiplesclerosisnewstoday.com, written by Marta Figueiredo and fact checked by Patrícia Silva, PHD.

MD1003MedDay Pharmaceuticals’ high-dose biotin therapy, failed to significantly improve functional ability or walking speed in people with non-active progressive multiple sclerosis (MS), according to data from a Phase 3 clinical trial.

Besides failing to meet the trial’s goals, the therapy was associated with inaccurate results in lab tests, which, if misinterpreted, may lead to serious complications inadvertently caused by an incorrect diagnosis and treatment, the researchers noted.

Based on these findings, the researchers advised against the use of MD1003 or commercially available high-dose biotin to treat progressive MS. MD1003’s clinical development has been stopped, according to MedDay’s website.

The trial’s full data were reported in the study, “Safety and efficacy of MD1003 (high-dose biotin) in patients with progressive multiple sclerosis (SPI2): a randomised, double-blind, placebo-controlled, phase 3 trial,” published in the journal The Lancet Neurology.

MD1003 is a highly concentrated oral formulation of biotin, a form of vitamin B found in food that helps the body break down fats, carbohydrates, and proteins. While biotin is often sold as a dietary supplement, MD1003 provides 10,000 times more biotin than the recommended daily dose.

Preclinical research showed that MD1003 prevented myelin loss and nerve cell death in a mouse model of MS, likely due to a dual effect on the activity of myelin-producing cells and in the metabolism of damaged nerve cells. Myelin is the protective sheath around nerve fibers that is progressively damaged and lost in MS.

Results from a previous, randomized Phase 3 trial, called MS-SPI (NCT02220933), indicated that one year of MD1003 treatment (a 100 mg capsule three times a day) safely and effectively lessened disability in people with non-active progressive MS, compared with a placebo.

Particularly, benefits were seen in patients’ disability level, measured by the expanded disability status scale (EDSS), and exercise capacity, assessed with the timed 25-foot walk (T25FW) test, which measures the time a person takes to walk 25 feet as quickly and safely as possible.

Follow-up data from participants continuing treatment or switching from placebo to MD1003 showed that the therapy resulted in sustained benefits up to three years and that early treatment was associated with greater improvements.

These positive findings supported the launch of the international Phase 3 SPI2 trial (NCT02936037) designed to confirm MS-SPI results in a larger, more representative group of progressive MS patients.

A total of 642 adults, who were relapse-free but showed evidence of disease progression, were randomly assigned to take either an oral 100 mg capsule of MD1003 (326 patients) or a placebo (316 patients), three times a day.

Treatment continued until all participants reached month 15 and underwent clinical assessment, after which all would receive MD1003 for up to 39 additional months (more than three years). Simultaneous treatment with other disease-modifying therapies was allowed during the trial.

The trial’s main goal was to assess whether MD1003 was superior to placebo at reducing patients’ disability (assessed with the EDSS) or improving their walking speed (measured with the T25FW test) at one year and confirmed three months later.

Secondary goals included time to disease progression, patient and clinician clinical global impression, and mean change in the T25FW test, while exploratory goals comprised brain imaging measures, blood levels of neurofilament light protein (a potential MS biomarker), daily step count (monitored remotely), and quality of life.

The study’s placebo-controlled phase lasted a mean of 20.1 months.

Results showed that a slightly greater proportion of MD1003-treated patients (12%) had less disability or could walk faster at one year, with confirmation at month 15, than those on a placebo (9%). However, this difference did not reach statistical significance.

Predefined subgroup analyses did not find “supportive data for a clinically meaningful effect of MD1003 in any particular subgroup,” the researchers wrote. Non-significant differences between groups were also found for all secondary and exploratory goals, indicating that the trial failed to meet all its goals and to replicate MS-SPI findings.

Concerning safety, MD1003 was well-tolerated, with a safety profile consistent with that reported in previous studies and with no unexpected safety concerns. Rates of adverse events were similar between the two groups of patients.

One person with multiple cardiovascular risk factors and initially assigned to the MD1003 treatment died, but this death was considered by the investigators to be unrelated to the therapy.

Moreover, despite implementation of multiple strategies to reduce the known occurrence of inaccurate laboratory results associated with high biotin levels in the blood, such results were recorded 25 times during the trial.

The most frequent error was related to the levels of thyroid gland hormones, inaccurately suggesting the presence of hyperthyroidism, a condition caused by the overactivation of the thyroid gland.

“When high-dose biotin is used off label, it could lead to deleterious health consequences to patients from misleading laboratory tests that, in turn, could lead to inappropriate medical interventions such as mismanagement of thyroid or cardiac conditions,” the team wrote.

“Therefore, MD1003, and by extension, off-label use of commercially available high-dose biotin, should not be used to treat progressive multiple sclerosis,” the researchers concluded.

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Julia Howell

Trustee

Julia is a qualified nurse and midwife, with a varied career including specialising in eating disorders, primary healthcare, and management.    

Julia, in partnership with a GP, set up an outpatient clinical trials unit (Southern Clinical Trials). Under her leadership this grew into a network of 6 sites across NZ. This network merged with another one in 2021 to form PCRN, NZ’s largest clinical trials network. Julia is currently working as joint COO for PCRN.

Julia’s daughter was diagnosed with MS aged 14 and she has been intimately involved with her management over the years.

 

Jan Campbell

Trustee

Born in Ōtautahi Jan trained as a nurse in Christchurch, as a midwife in Winchester, UK and has a degree in philosophy with particular interest in healthcare and business ethics.

After working in the public health system in the UK and NZ, Jan joined Roche Pharmaceuticals based in Auckland in 1999. As a respected senior leader and Medical Director, she established a medical division over the ensuing 20 years responsible for significant investment in clinical trials in NZ, developing a top-class global medicine information service, compassionate medicine supply for kiwis in need, pharmacovigilance oversight and a team working closely with patients, specialists, MEDSAFE and PHARMAC to support the safe and appropriate use of Roche medicines.

As a retiree Jan has volunteered for Mercy Hospice in Auckland and the WBoP Museum in Katikati. Now living in Ōtepoti, Jan sits on both the MS Research Trust and MSNZ executive committees with a keen interest to ensure people with MS get a fair go in NZ.

Dr Elza Cloete

Trustee

Elza is a Neonatal Paediatrician at Christchurch Women’s Hospital. Originally from South Africa, she moved to New Zealand in 2006 and completed her specialist training in Auckland.

Subsequent to that she embarked on doctoral studies at the University of Auckland’s Liggins Institute and obtained a PhD investigating congenital heart disease in new-born babies.

Elza received the Vice-Chancellor’s award for best doctoral thesis for her research and is the author of several research publications. She moved to Christchurch in 2020 for a work opportunity in clinical practice.

Elza was diagnosed with MS in 2012 and brings a consumer perspective and research experience to the Trust.

Dr Ernie Willoughby

Trustee

Dr Willoughby has been a consultant neurologist at Auckland City Hospital (1979 to 2021 – now retired, emeritus) and clinical associate professor at Auckland University School of Medicine.

He directed the MS clinic at Auckland Hospital, has had a long association with the Auckland and NZ MS Societies, and is a member of the International Medical and Scientific Board of the MS International Federation.

Dr Brian Linehan

Independent Trustee

Dr Brian Linehan is a retired pathologist who was previously Managing Director of Medlab Hamilton.

He is currently Chairman of the Tranmere group of investment companies and a Director of a number of other private companies. In 2014, he retired after 12 years on the Council of the University of Waikato where he was Pro-Chancellor.

He is a past Chairman of the New Zealand Medical Association, past Chairman of NZMA Ethics Committee, past President and Chairman of CMAAO (Combined Medical Associations of Asia and Oceania) and past Chairman of IANZ (International Accreditation NZ).

Brian was diagnosed with MS in 2007 but is still active and mobile.

Peter Wood - JP, BCom, AGNZ, ACIS, FNZTA

Treasurer

Peter gained his commerce degree at Victoria University of Wellington and has been practising as a Chartered Accountant initially in Wellington and then in Tauranga.

Peter was a respected and trusted advisor to many businesspeople.
He is now resident in Auckland and consultants to a limited number business clients.

He has also served his community through involvement with Jaycees, Lions and Rotary clubs and a number of charitable trusts.

Peter is currently the Treasurer of Multiple Sclerosis Auckland and a trustee of the Multiple Sclerosis Auckland Trust. Peter is a Justice of the Peace and a member Governance New Zealand and is a Fellow of the NZ Trustees’ Association.

Neil Woodhams

Trustee

Neil is an independent health management consultant who has had an extensive career in health management as a senior manager or consultant to government, DHBs, primary care and community providers. 

Neil is President of MS New Zealand and a trustee of the MS Auckland Region Trust. Neil was also President of MS Auckland until he stepped down from this role mid-2020 to concentrate on his national roles.

Neil’s wife was diagnosed with MS in 1994. One of his four sons was also diagnosed in 2010.

Neil strongly believes in the objectives of the NZ Multiple Sclerosis Research Trust and has advocated for the establishment of the Trust for over 10 years.

Sir William Gallagher

Trustee

Sir William is renowned as a motivational, pragmatic and hands-on businessman in and outside of New Zealand and has a reputation both as a dynamic leader and one of NZ’s most astute businessmen.

Still very involved in the daily operation, he maintains regular contact with customers in the 130 countries in which Gallagher products are sold spending up to 150 days a year on the road representing the company and its philosophies and emphasising the ethics and integrity of his professional and personal dealings.

His achievements have been officially recognised by a string of awards, the latest to mark his commitment to enterprise and leadership skills being his Knighthood in the 2010 New Year’s Honours List. He was also the 1996 winner of the prestigious Excellence in Communication Leadership award, the first time in its history that it had been awarded outside of North America. He also received an MBE in 1987 followed by a Companion of the New Zealand Order of Merit (CNZM) in 1998.

Sir William Gallagher - KNZM, MBE. HonD

Patron

Sir William is renowned as a motivational, pragmatic and hands-on businessman in and outside of New Zealand and has a reputation both as a dynamic leader and one of NZ’s most astute businessmen.

Still very involved in the daily operation, he maintains regular contact with customers in the 130 countries in which Gallagher products are sold spending up to 150 days a year on the road representing the company and its philosophies and emphasising the ethics and integrity of his professional and personal dealings.

His achievements have been officially recognised by a string of awards, the latest to mark his commitment to enterprise and leadership skills being his Knighthood in the 2010 New Year’s Honours List. He was also the 1996 winner of the prestigious Excellence in Communication Leadership award, the first time in its history that it had been awarded outside of North America. He also received an MBE in 1987 followed by a Companion of the New Zealand Order of Merit (CNZM) in 1998.