Late-breaking ECTRIMS 2016 session unveils new biomarkers, real-world treatment comparisons, and clinical trial results

Each year ECTRIMS ends with a bang as late-breaking research news is presented first thing in the morning. Presenters at the late-breaking news session deliver the newest key findings of pivotal studies and clinical trials. At the session, we heard about a new potential biomarker that can help evaluate the success of progressive MS trials, the effectiveness of available MS disease-modifying therapies in the real world, and topline results from clinical trials of emerging progressive MS and symptom management treatments. Read on for highlights from the ECTRIMS late-breaking news session.

img_7013

New data positions neurofilament light chain as strong biological indicator of MS disease outcomes

Neurodegeneration is a major component of multiple sclerosis, particularly in progressive MS where ongoing, irreversible neurodegeneration contributes to disability. When nerves are damaged, proteins that make up the nerves are released into the cerebrospinal fluid (CSF) and blood. Dr. Jens Kuhle from Basel, Switzerland presented a technique that his team used to measure levels of a protein called neurofilament light chain (NfL) in blood samples from people living with MS who were part of FREEDOMS – a phase III clinical trial for fingolimod. His research team investigated whether blood NfL levels differed between people with MS and healthy controls, and if they can inform clinical outcomes. They found that levels of blood NfL were significantly higher in people with relapsing remitting MS compared to healthy controls, and were positively correlated with the number of lesions, size of lesions, relapses, and EDSS, a measure of disability. The data presented showed that NfL predicted brain atrophy rates, and those treated with fingolimod had lower blood NfL levels than those who were not treated with fingolimod. Together these findings position blood NfL as a promising, sensitive biomarker for neurodegeneration that offers a faster and less invasive alternative to sampling from the CSF.

Phase III clinical trial results for experimental progressive MS treatment siponimod

Dr. Ludwig Kappos presented the most recent results from EXPAND – a phase III double-blind, randomized, placebo-controlled clinical trial investigating a treatment called siponimod developed by Novartis. Siponimod works by keeping immune cells inside the lymph nodes, preventing them from entering the brain and spinal cord where they can cause damage to myelin. Siponimod can also enter the brain and spinal cord where it is thought to promote repair and neuroprotection. As the largest secondary-progressive MS trial to date, EXPAND involved 1,651 participants with SPMS across 31 countries who received either oral siponimod at a dose of 2mg once daily, or placebo. Dr. Kappos reported that treatment with siponimod reduced the risk of disability progression by 21% when looking at EDSS changes over 3 months, and by 26% when looking at EDSS changes over 6 months. Positive effects were observed for both those who had experienced prior relapses as well as those without prior relapses. The strongest effect was seen in those with very active disease and lower EDSS at baseline. Treatment with siponimod also resulted in significant reductions in annual relapse rate and magnetic resonance imaging (MRI) measures such as changes in brain atrophy and lesion volume. However, there was no significant difference between treatment and placebo groups on performance in the timed 25-foot walk test. The safety profile of siponimod was in line with similar therapies. Analysis of the data is still ongoing, and we’ll be keeping a close eye on new findings as they become available.

Real-world data from MS registry allows researchers to compare treatments

As more treatments are approved for MS, it becomes increasingly important for clinicians to rely not only on clinical trial to inform treatment decisions, but also “real world” evidence once these treatments are available to thousands of people. Dr. Tomas Kalincik from Australia presented 5-year treatment outcome data for alemtuzumab and compared it to data on natalizumab, fingolimod, and interferon beta-1a. Researchers collected data from MSBase – a large repository of MS data collected by neurologists around the world and used for clinical and research purposes.  Information from MSBase on close to 4,000 patients was retrospectively analyzed. Patients with matching demographic and disease characteristics were compared to determine how well they did on the treatments of interest. Dr. Kalincik reported that, compared to interferon, alemtuzumab was associated with fewer relapses, although overall there was no change in the risk of disability progression. However, those treated with alemtuzumab who had highly active MS were more likely to experience a reduction in disability progression compared to those on interferon. Researchers also found that alemtuzumab was associated with fewer relapses when compared to fingolimod, although there was no significant difference in disability progression. Finally,there was no significant difference in relapses observed between those treated with alemtuzumab versus natalizumab, but natalizumab was associated with greater reduction in disability in the first year of treatment. Overall, the results of this study, which captures real world data on treatment responses, replicated what was observed in clinical trials comparing alemtuzumab to interferon beta-1a, and provides strong evidence demonstrating a superior effect on reducing relapses when compared to fingolimod. Alemtuzumab and natalizumab showed similar effects on relapse activity, although natalizumab was associated with a greater short-term reduction in disability.

Lifestyle and environmental risk factors for MS explored in CIS cohort

Dr. Maria Zuluaga from Barcelona presented data on the influence of vitamin D deficiency and smoking on risk of developing confirmed MS and disability progression among individuals with early signs of MS (clinical isolated syndrome or CIS). Her team collected clinical and imaging data from a large CIS cohort in Barcelona established in and followed from 1995 onward. Vitamin D and cotinine levels (the latter being a biomarker for smoking) were analyzed in blood serum samples of people following diagnosis of CIS. In 503 patients who were studied, the researcher reported that 72% had low vitamin D levels (less than 20ng/ml). Levels of otinine in the “active smoker” range were present in 43% of patients. Overall, they found that vitamin D deficiency was not associated with an increased risk of developing confirmed MS; however, severe vitamin D deficiency (less than 8ng/ml) was associated with disability progression in patients with CIS. They also reported that non-smokers with CIS had lower risk of disability progression, but were not at lowered risk of developing confirmed MS. Overall their research suggests that smoking and low vitamin D levels independently contribute to disability accumulation in people with CIS.

Improvements in walking ability observed in clinical trial for prolonged-release fampridine

Dr. Jeremy Hobart from the UK shared results from ENHANCE, a clinical trial investigating whether prolonged-release fampridine can bring about sustained, clinically meaningful benefits in people with MS. Fampridine is an oral treatment that has been shown to improve walking in people living with MS, although questions remain about whether these improvements are clinically meaningful. ENHANCE is the longest randomized, phase III trial of fampridine to date. It involved 636 relapsing-remitting and progressive MS patients (average EDSS of 6.0), who were given either 10mg fampridine twice a day or placebo. The researchers looked at the proportion of people who showed improvements in the 12-item MS Walking Scale (MSWS-12) score (a self-reported measure of walking ability) over 24 wks. They also looked at secondary measures of mobility, balance, and upper limb function among the treatment and placebo groups. Results of the trial revealed clinically meaningful improvements in walking in 43% of people treated with fampridine, versus 34% of people treated with placebo. Significant differences were also observed for walking speed, upper limb function, and self-reported physical impact in the treatment group versus placebo. No new safety concerns were reported.

 

Leave a Reply

Your email address will not be published. Required fields are marked *