Back to the Drawing Board: MedDay's MS Therapy Fails in Phase III Trial
The trial, dubbed SPI2, evaluated the safety and efficacy of three daily doses of 100mg of MD1003 compared to placebo in 642 patients with progressive MS without recent relapses, which is also called not-active progressive MS. The primary endpoint was reversal of functional disability, which was measured by the proportion of patients with an improvement in either the Expanded Disability Status Scale (EDSS) or in how long it took patients to walk 25 feet (TW25) over a 12-month time frame and then confirmed at 15 months.
Secondary endpoints were the relative decrease in the risk of disability progression, global impression of response to the drug as evaluated by both the patient and their physician, and the mean change in TW25. Other exploratory endpoints included brain MRI measures, quality of life measures and measurements of ambulation using a Fitbit wearable device.
MD1003 is a neurometabolic modulator that targets both neurodegenerative and demyelination processes through a non-immunological mechanism.
“We are clearly disappointed that SPI2 did not meet its primary and secondary endpoints,” said Catherine Moukheibir, MedDay’s chief executive officer. “Going forward, we will continue to evaluate the trial data and confer with regulators. We would like to thank our collaborators including the participating clinicians, medical staff and, most importantly, the patients for all of their efforts and participation in the trial. All were invaluable partners throughout the process of completing the SPI2 trial.”
MD1003 is also being evaluated in Charcot-Marie-Tooth disease and in hepatic encephalopathy. The company also acquired the SPECMET metabolic platform that is in preclinical development for amyotrophic lateral sclerosis (ALS) and brain aging. In 2018, the company acquired the health division of Profilomic SA, a spin-off company from the Comite d’Energie Atomique (CEA). This allowed MedDay to extend its database and laboratory equipment with a team of researchers with expertise in metabolomics and lipidomics. SPECMET created a biobank of 700 cerebrospinal fluid (CSF) samples from all major neurodegenerative diseases, including rare inborn errors of metabolism.
MS is an autoimmune disease where the patient’s immune system attacks myelin, the substance that coats nerve fibers in the brain and spinal cord. Most clinical therapies involve tweaking the immune system, but MD1003 targets metabolic pathways, stimulating the Krebs cycle to give more energy to demyelinated nerve fibers with the hopes of boosting the developing of an insulating layer of myelin. The Krebs cycle, also known as the citric acid cycle or the TCA cycle, is a chain of chemical reactions used by all aerobic organisms to release stored energy.
“We will review the findings in detail to understand these outcomes to help inform future clinical research in progressive MS and other neurological diseases,” said Frederic Sedel, chief scientific officer and co-founder of MedDay. “I remain confident of the importance of the neurometabolic approach to neurodegenerative diseases with high unmet medical need.”
The company is presenting detailed data from the trial on April 29 in Toronto, Ontario, Canada, at the American Academy of Neurology (AAN) 2020 Annual Meeting.