Perhaps the most anticipated session at ECTRIMS is “Late Breaking News”, which features a selection of exciting and newly released clinical trial results as well as data from preclinical studies. This year’s conference has been notable for launching a number of late-breaking results that have been described by numerous respected MS researchers as “game-changers” in the field of MS with the potential to offer new, effective, and accessible treatments for people living with different forms of MS. Read on to see what everyone’s talking about at this year’s ECTRIMS conference.
Ocrelizumab poised to become the first disease modifying therapy to treat primary progressive MS
The results of ORATORIO, a Phase III, randomized, double-blind, placebo controlled study led by Dr. Xavier Montalban (Hospital Vall d’Hebron University, Barcelona, Spain) and a large team of international investigators (including Canadians Drs. Amit Bar-Or and Anthony Traboulsee), were unveiled today and were met with great enthusiasm from the scientific and patient communities. The trial, which examined the efficacy and safety of an emerging B-cell targeting drug ocrelizumab in 732 participants with primary progressive MS, met its primary endpoint of significantly reducing progression of clinical disability (measured by the Expanded Disability Status Scale) by 24% at 12 weeks and 25% at 24 weeks compared with a mock treatment (placebo). Additionally, ocrelizumab was superior to placebo in a number of additional endpoints. It significantly reduced the time required to walk 25 feet (measured using the Timed 25-Foot Walk test) over 120 weeks by 29%., and decreased the volume of T2 lesions by 3.4% over 120 weeks, compared to placebo which increased T2 volume by 7.4%. Ocrelizumab reduced the rate of whole brain volume loss over 120 weeks by 17.5% compared to placebo. Adverse events were similar in the treatment and placebo groups. The most common adverse event in the treatment group was infusion-related reactions. The therapy was found to be safe with few major adverse events compared to placebo. Together this positive data positions ocrelizumab as a promising candidate for the treatment of primary progressive MS.
MT-1303 reduces brain lesions and relapse rate in people with relapsing remitting MS
Data from a Phase II proof-of-concept clinical trial (MOMENTUM) evaluating the experimental drug MT-1303 or amiselimod in people living with relapsing remitting MS were presented by Dr. Ludwig Kappos (University Hospital Basel, Basel, Switzerland) and his team including Canadians Drs. Douglas Arnold and Amit-Bar-Or (McGill University, Montreal, QC). The trial compared 3 doses of MT-1303 to placebo in 415 participants over a 24 week period and found that the drug dose-dependently reduced the number of lesions in the brain (24% reduction at 0.1mg, 55% reduction at 0.2mg, and 77% reduction, which was most significant, at 0.4mg). It also decreased the annualized relapse rate and grey matter loss at higher doses. Number of white blood cells on blood test were also reduced. Overall there were no adverse effects reported, and cardiac event, which are of particular interest, were similar across treatment arms and in the placebo group.
Rigorous reanalysis of data from previous trial shows that teriflunomide slow brain tissue loss in people with relapsing remitting MS
Teriflunomide (Aubagio) is a once-daily oral medication approved for the treatment of relapsing-remitting MS. Although an earlier Phase III clinical trial (TEMSO) showed reduced risk of disability progression in participants with relapsing remitting MS taking teriflunomide, the investigators were surprised to find no reduction in brain tissue loss, which normally links up closely with disability progression. Dr. Till Sprengler (University Hospital Basel, Switzerland) presented data that was rigorously re-analyzed using a powerful, automated technique showing that teriflunomide did in fact reduce the rate of brain tissue loss after both 1 and 2 yearsas originally hypothesized, providing structural evidence in the brain of the benefits of the drug. This data confirms that teriflunomide remains an important once-daily oral treatment option for people with relapsing remitting MS.
Anti-LINGO-1 shows some evidence of protecting against vision loss in people with acute optic neuritis
Anti-LINGO-1, also known as BIIB033, is a promising experimental antibody being studied in MS trials for its potential remyelinating and neuroprotective properties. Dr. Diego Cadavid (Biogen, Cambridge, MA) and team presented data from the RENEW trial in participants with acute optic neuritis. Although early data has been previously reported at the American Academy of Neurology, the investigators used a sophisticated technique to measure function of the visual pathway in the brain for both the affected and unaffected eyes. The results showed that the unaffected eye at baseline was protected from potential degradation in visual function in people taking Anti-LINGO-1 after 32 weeks compared to those taking placebo. These results suggest that Anti-LINGO-1 is a promising candidate for reducing the risk of vision loss in individuals affected by acute optic neuritis.
MD1003 can potentially improve disability and decrease risk of progression in people with secondary progressive MS
MD1003, an ultra-high dose formulation of biotin (vitamin H), has recently come under study due to its role in promoting new myelin formation and enhancing energy supply. The MS-SPI trial compared disability progression in participants with primary and secondary forms of progressive MS to those taking placebo after 48 weeks. The data, presented by Dr. Ayman Tourbah (Centre hospitalier universitaire de Reims, France), showed that some participants taking MD1003 had improvements in disability measures compared to none taking placebo. The best responders to MD1003 were those were relatively lower disability and those with secondary progressive MS. Those taking the fampridine (a drug that can improve walking speed in some individuals living with MS) at the same time as MD1003 benefit in terms of their disability progression compared to those taking only fampridine. Preliminary data showed that the effect of treatment was maintained after 18 months.
Repurposed oral antibiotic reduces risk of converting from first clinical demyelinating event to MS
Dr. Luanne Metz (University of Calgary, Calgary, AB) presented new data from a phase III, randomized, double-blind, placebo-controlled clinical trial investigating the efficacy of minocycline in reducing the risk of conversion to MS in people who have experienced a first clinical demyelinating event called clinically isolated syndrome (CIS). Minocycline is a commonly used, inexpensive antibiotic with a good safety track record. Since treating a first clinical demyelinating event as early as possible is a key step in reducing the likelihood of developing MS, access to an effective and low-cost treatment can go a long way. The trial enrolled 142 participants who were randomly selected to receive oral minocycline at a dose of 100mg twice a day or a dummy medication. Dr. Metz and her team found that treatment with minocycline reduced the relative risk of converting to MS in those with a first clinical demyelinating event by almost 45% compared to placebo. The clinical trial is funded by the MS Society of Canada and MS Scientific Research Foundation. We will report on the published results in a scientific journal as they become available.
Preliminary preclinical shows that certain short chain fatty acids stimulate a beneficial immune conditions in the body
This early study in humans investigated the effect of propionate, a short chain fatty acid found in certain food additives approved in North American and Europe, on the balance of “good” and “bad” immune cells in healthy participants. Oral propionate capsules were taken by 18 participants (including the study author Dr. Aiden Haghikia, Ruhr-University Bochum, Germany), and proportions of certain immune cell types were measured in the blood. Dr. Haghikia and his team showed that propionate significantly increased the levels of “good” immune cells called regulatory T cells while decreasing “bad” cells, suggesting that propionate has the potential to complement established disease-modifying treatments for people living with MS by creating favourable immune conditions in the body, potentially by promoting a healthy population of bacteria residing in the gut.