Insights into Promising MS Therapies at Late Breaking News Session, ECTRIMS 2015
A session titled “Late Breaking News” was featured at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Oct. 7-10, 2015, in Barcelona, Spain. At this session, Prof. Xavier Montalban from the Hospital Vall d’Hebron University in Barcelona presented data on the promising Genentech/Roche therapy ocrelizumab (to learn more, please follow the link).
The session included several other presentations. The first was given by Prof. Ludwig Kappos from the University Hospital Basel, Switzerland, and was titled “Results of MOMENTUM, a randomised, double-blind, placebo-controlled, Phase 2 trial with MT-1303, a novel selective sphingosine 1-phosphate receptor 1 (S1P1) modulator, in relapsing-remitting MS”.
MT-1303 is a new selective S1P1 antagonist in development for relapsing-remitting multiple sclerosis (RRMS). MT-1303 prevents lymphocytes from participating and contributing to autoimmune reactions. Prof. Kappos presented Phase 2 clinical trial results showing that MT-1303 can reduce the cumulative number of brain MRI lesions in RRMS patients after 24 weeks of treatment. This effect was dose-dependent, with higher doses of MT-1303 (tested at 0.1, 0.2 or 0.4 mg) offering a higher reduction in the total number of lesions. Furthermore, MT-1303 treatment also resulted in a decrease in grey matter volume loss, and “Significant reductions of the annualized relapse rate (ARR) after 24 weeks with higher doses of the S1P1 modulator” said Prof. Kappos. In terms of safety, “No differences in adverse events across different dosage groups and placebo” were observed, noted Prof. Kappos. MT-1303 efficacy and safety profile support that it could be considered a promising new therapy for RRMS.
In another presentation, Dr. Luanne M. Metz from the University of Calgary, Canada reported on her work on minocycline – “Minocycline reduces the relative risk of multiple sclerosis in people experiencing their first clinical demyelinating event by 44.6%: results of a phase III double-blind placebo controlled Canadian multicentre clinical trial”.
Dr. Metz showed that minocycline, a safe oral antibiotic, can be considered a therapeutic option for MS as either a monotherapy or an add-on treatment in patients experiencing the first occurrences of myelin damage (demyelination), before MS development. She reported that minocycline can successfully reduce the conversion of the first clinical demyelinating events to MS. “By 6 months, minocycline reduces the absolute risk of MS by 27.4% and the relative risk by 44.6%. It is a safe, well-tolerated, inexpensive oral therapy that should be considered for the treatment of first demyelinating events” concluded Dr. Metz.
Prof. E. W. Radue and Prof. Till Sprenger from the University Hospital Basel, Switzerland, also presented their work titiled “Teriflunomide slows brain volume loss in relapsing MS: a SIENA analysis of the TEMSO MRI dataset”.
Teriflunomide (Aubagio), an oral compound that inhibits the function of specific immune cells implicated in MS, was previously shown to reduce the risk of disability progression in patients with relapsing MS. Now, researchers analyzed the impact of teriflunomide on brain volume loss in these patients using a specific technique called SIENA (structural image evaluation using normalization of atrophy). It was shown that teriflunomide (at 7 and 14 mg doses) significantly reduced brain volume loss in comparison to a placebo over a period of 2 years. “Teriflunomide 7 mg vs placebo at year 1 resulted in a 34.4% reduction in brain volume loss” said Prof. Sprenger, and a 27.6% reduction at year 2; on the other hand, teriflunomide 14 mg induced a 36.9% and 30.6% reduction at year 1 and 2, respectively. The results strengthen the efficacy of teriflunomide as a therapy for relapsing MS.
Another presentation was given by Dr. Aiden Haghikia from Ruhr-University Bochum, Germany, titled “Impact of fatty acids on CNS autoimmunity and their therapeutic potential for multiple sclerosis”.
Dr. Haghikia started her talk by asking, “Fatty acids: does the length matter for T-cell autoimmunity? Yes”. According to her, the “fate of naïve T-cell differentiation depends on the aliphatic chain length. Longer chain fatty acids enhance differentiation of Th17 cells”, which are immune cells involved in MS pathogenesis. Dr. Haghikia showed that while long chain fatty acids have a detrimental effect on MS disease course, short chain fatty acids, like propionate, ameliorate MS symptomatology in a mouse model of the disease by promoting the differentiation of Tregs (regulatory T cells) in the gut. Furthermore, the intake of propionate in humans was found to increase by 25 to 30% the levels of Tregs and significantly decrease Th17 cells. Dr. Haghikia concluded that nutrition can influence the systemic immune system, and suggested that it should be explored further in combination with established disease modifying drugs for the treatment of autoimmune diseases like MS.
Dr. Ayman Tourbah from the Université de Reims Champagne-Ardenne (URCA), France gave the final presentation of the session, titled “MD1003 (high doses of biotin) in progressive multiple sclerosis: subgroup analyses of the MS-SPI trial”.
MD1003 is an experimental drug with pro-myelinotic properties that acts by activating acetyl-CoA carboxylases (ACC1 and ACC2), which are the rate-limiting enzymes in the fatty acids synthesis required for myelin formation. Dr. Tourbah showed results from the MS-SPI trial in patients with progressive MS (primary and secondary), where MD1003 was found to significantly improve MS-related disability and reduce disease progression in comparison to a placebo treatment. This positive clinical effect seemed to be more pronounced in patients with secondary progressive MS. Dr. Tourbah concluded his presentation by stating that MD1003 might be a valuable therapeutic approach for progressive forms of MS.