Trial results

High levels of satisfaction with the efficacy and convenience of Aubagio (teriflunomide), an oral treatment for relapsing multiple sclerosis (MS), were reported by patients across the U.S. and 13 other countries, a post-hoc analysis of data from a real-world Phase 4 study found. The study “Teriflunomide real-world evidence: Global…

In clinical practice, relapse events dropped by roughly half over a four-year period in relapsing-remitting multiple sclerosis (RRMS) patients treated with Aubagio (teriflunomide), a real-world study reports. The study, “Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study,” also examined patients’ perspectives in…

Researchers have developed a compound based on the thyroid hormone T3 that is able to repair damaged myelin in the brain of mice, a discovery that holds promise for healing myelin loss in patients with multiple sclerosis (MS), results of an early study reveal.

The National Multiple Sclerosis Society has recently awarded $24.4 million in grants to support 64 research projects on multiple sclerosis (MS) worldwide, including $750,000 to fund 14 high-risk, high-reward pilot projects that will test new ideas and seek answers to new and relevant questions. According to a society…

Tecfidera (dimethyl fumarate) is more efficient at preventing relapses, and has a lower discontinuation rate than Aubagio (teriflunomide), according to a Danish study. The study “Comparative effectiveness of teriflunomide and dimethyl fumarate: A nationwide cohort study” was published in the journal Neurology. Aubagio (marketed by Sanofi Genzyme) and Tecfidera…

Treatment with oral ibudilast slows brain shrinkage in patients with primary progressive multiple sclerosis (PPMS), but not in those with secondary progressive MS (SPMS), according to results of a Phase 2b clinical trial. According to the findings, this could be partially due to faster disease progression in untreated…

Treatment of relapsing multiple sclerosis (MS) with beta-interferon therapies is associated with extended patient survival, particularly if taking such treatments for more than three years, according to a real-world study in Canada and France. The study, “Multiple sclerosis: effect of beta interferon treatment on survival,” was…

Treating multiple sclerosis with Tecfidera induces specific genetic alterations that may reduce the levels of immune T-cells targeting the central nervous system, researchers report. Environmental stimuli may induce epigenetic changes in cells — meaning not alterations in the genes themselves, but changes in gene expression (the process by which information in a gene is synthesized to create a working product, like a protein). Epigenetic changes may induce MS development, as these alterations can cause T-cells to attack the central nervous system. One type of epigenetic change is DNA demethylation, the removal of methyl chemical groups, in which molecules involved in metabolism (such as fumarate) interact with enzymes known as DNA demethylases. This process in key for T-cell activation, function and memory, suggesting that it could be an immunomodulatory target. Fumaric acid esters were shown to be effective in MS clinical trials, leading to the approval of Tecfidera (by Biogen) for people with relapsing-remitting forms of the disease. However, their complete mechanism of action remains unclear. Aiming to address this gap, scientists at the Advanced Science Research Center (ASRC) at The Graduate Center of The City University of New York and the Icahn School of Medicine at Mount Sinai, recruited 98 MS patients, either previously untreated (47 people, mean age of 38.4), treated with Tecfidera (35 people, mean age of 42.3), or treated with glatiramer acetate (16 patients, mean age of 43.4) — marketed as Copaxone by Teva Pharmaceuticals, with generic forms by Sandoz (as Glatopa) and by Mylan. All patients had stable disease for at least three months, but disease duration was shortest in untreated patients — 40.4 months vs. 130 months in those given Tecfidera, and 100 months in patients using glatiramer acetate. Blood samples were collected from each participant to assess epigenetic changes in T-cells expressing the cell surface marker CD4. MS patients typically have an activated form of these cells in their blood and cerebrospinal fluid, the liquid surrounding the brain and spinal cord. Results revealed that, compared to the other two groups, treatment with Tecfidera was associated with a lower percentage of T-cells containing the CD3, CD4, and CD8 markers, as well as lower levels of subsets of T-cells expressing the CCR4 and CCR6 receptors, which are critical to T-cell migration to the gut, brain, and skin. Treatment with glatiramer acetate resulted in significantly milder alterations in T-cell percentages compared to no treatment. Researchers then found that FAEs induce excessive methylation — the addition of methyl groups — in T-cells containing CD4, compared to glatiramer acetate. Specifically, this overmethylation was observed in a micro-RNA — tiny RNA molecules than control gene expression — known as miR-21, key for the differentiation of a subset of T-cells called T helper-17 (Th17) cells and for CCR6 expression in MS mouse models. These Th17 cells are critical in tissue inflammation and destruction, and have been implicated in MS. The epigenetic effects of FAEs were subsequently validated by comparing pre- to post-treatment with Tecfidera in seven patients. In turn, in vitro (lab dish) experiments showed that FAEs act specifically on the activation of naïve T-cells — those able to respond to new pathogens to the immune system — containing the CD4 or the CD8 markers. Of note, patients with MS have shown increased miR-21 levels, particularly during acute relapses. As such, the team hypothesized that its hypermethylation by FAEs could contribute to remission and the prevention of relapses in this patient population. These results "suggest that the metabolic-epigenetic interplay in T-cells could be harnessed for therapeutic purposes," the researchers wrote, and that the immunomodulatory effect of FAEs in MS is due at least in part to the epigenetic regulation of T-cells. The researchers believe that their findings have a broader implication, beyond MS. "Our findings about therapeutically active metabolites have implications for the treatment of not only multiple sclerosis but also other autoimmune diseases, such as psoriasis and inflammatory bowel disease, which involve the same type of T-cells," Achilles Ntranos, the study’s lead author, said in a press release. "Understanding the epigenetic effect of metabolites on the immune system will help us develop several novel strategies for the treatment of autoimmune diseases, which could help patients and physicians achieve better clinical outcomes," Ntranos added. Patrizia Casaccia, the study’s senior author, concluded: "It may one day be possible to target and suppress production of the specific brain-homing T-cells that play a role in the development of MS."

Full results of a Phase 2 clinical trial testing TG Therapeutics’ lead candidate ublituximab (TG-1101) for relapsing multiple sclerosis (MS) showed that treatment for 48 weeks resulted in a marked reduction of brain and spinal cord lesions, an almost complete depletion of relapse-associated immune B-cells, and significantly halted disability…

Evobrutinib, Merck KGaA’s oral candidate for relapsing multiple sclerosis (MS), is safe and can significantly reduce active brain lesions over 24 weeks of treatment, results of ongoing Phase 2 study show. Xavier Montalban, PhD, MD, with Vall d’Hebron University Hospital in Barcelona, presented the results in the talk “Primary…

Data supporting the off-label use of rituximab in adolescents with pediatric-onset multiple sclerosis (POMS) was presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2019. The session, titled “No Evidence of Disease Activity in the Majority of Pediatric-Onset Multiple Sclerosis Patients Receiving Rituximab,”…

Stable patients with multiple sclerosis (MS) who transition from Tysabri (natalizumab) treatment to Aubagio (teriflunomide) have a lower relapse risk, a new study shows. The study, “Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy,”…

Aubagio (teriflunomide) seems to be superior to Tecfidera (dimethyl fumarate) in slowing whole brain shrinkage in patients with relapsing multiple sclerosis (MS), a new Phase 4 clinical trial shows. However, Aubagio and Tecfidera have similar beneficial effects in achieving other clinical goals and magnetic resonance imaging (MRI) parameters,…

Multiple sclerosis (MS) patients given intensive disease-modifying therapies early in their disease course have more favorable long-term outcomes than those treated with an escalating regimen, real-world data shows. The study, “Clinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis,” was published in the journal …

Multiple sclerosis patients who began treatment with Gilenya and stayed with it continuously showed a more than 50 percent reduction in annual relapse rates, a real-world study following these people for up to three years found. Gilenya, marketed by Novartis, is an oral disease-modifying treatment for relapsing-remitting multiple sclerosis , approved in 2010. It acts by binding and modulating receptors — called sphingosine-1-phosphate receptor — on lymphocytes (adaptive immune cells). By binding to these receptors, Gilenya prevents lymphocytes from leaving the lymph nodes and reaching the brain and spinal cord, and so lower lymphocyte-induced inflammation and damage. Although several clinical trials have reported reduced annualized relapse rates (ARRs) upon treatment with Gilenya, few long-term real-life studies have examined the relapse rate reductions over a long term. A team, led by Novartis researchers and a scientist at Central Texas Neurology Consultants, collected MS patient data from the MarketScan database, a U.S. claims database including medical and pharmacy claims (bills submitted to health insurance providers), between 2009 and 2016. Among 9,312 MS patients in the database with at least one filled Gilenya prescription, 1,599 adults (mean age, 46) met the study's inclusion criteria, including having at least one inpatient or two outpatient claims, and a total of four years of continuous health plan enrollment. Among these 1,599 patients, all used Gilenya for one year (cohort 1), 1,158 (72.4%) took Gilenya continuously up to the start of year two (cohort 2), and 937 (58.6%) used the therapy up to the start of year three (cohort 3). Baseline analysis — measures taken at the study's start — showed that the most common MS-linked symptoms were disorders of the optic nerve and visual pathways (reported in 22-24%), followed by fatigue/malaise (20-21%). Hypertension (20-21%) and depression (15-16%) were the most common physical and mental comorbidities, respectively. The mean annualized relapse rates (AARs) at baseline in these three groups of patients — cohorts 1 to 3 — ranged between 0.48 and 0.51. A consistent reduction in ARRs was seen in all three groups: cohort 1 had a 0.25 ARR at the close of the first year, for a 51% reduction from the baseline rate; cohort 2 a 0.22 ARR at the start of year two, for a  54% lowering in relapse rates from baseline; and cohort 3 had 0.23 ARR at the third year, amounting to a 53% reduction. As expected, when researchers calculated ARRs among patients with continuous Gilenya use over these three years, they found a greater reduction in annual relapse rates. Mean ARRs in continuous-use patients were 0.19 (a 61% reduction) during the first year, 0.18 (a 62% reduction) during the second year, and 0.18 (a 61% reduction) at the start of the third year. “This retrospective claims database study found that patients with MS who received fingolimod [Gilenya] therapy experienced a durable and sustained reduction in relapse rates over a 3-year period,” the researchers wrote, with findings representing “a durable reduction in relapse rates by [more than] 50%.” Reasons that some patients discontinued treatment were not a focus of this study, they added.

Rehabilitation using traditional dysphagia therapy improved swallowing function in multiple sclerosis patients with dysphagia, a pilot study shows. The research article with that finding, “The effect of traditional dysphagia therapy on the swallowing function in patients with Multiple Sclerosis: A pilot double-blinded randomized controlled trial” was…

Gilenya is linked to significantly lower annualized relapse rates in relapsing-remitting multiple sclerosis (RRMS) patients compared to Tecfidera or Aubagio, a study suggests. All three therapies showed similar effects on disability outcomes. Oral immunotherapies — including Novartis’ Gilenya, Biogen’s Tecfidera, and Sanofi Genzyme’s Aubagio — are currently standard therapies for RRMS treatment. But while these therapies are highly effective at modulating MS activity, studies comparing their efficacy on relapse and disability are missing. This is an important point for MS patients, so that if a change in oral therapies is needed (due to lack of tolerance, for example), the decision on a more suitable therapy is based on scientific evidence. To address this matter, a group of researchers used the MsBase, an international observational MS cohort study, to identify RRMS patients who had been treated with Gilenya, Tecfidera, or Aubagio for at least three months. The team compared Tecfidera versus Aubagio, Gilenya versus Aubagio, and Gilenya versus Tecfidera, specifically for the therapy’s impact on relapse activity, six-month disability worsening or improvement, and persistence of treatment. Relapse was defined as the occurrence of new symptoms or exacerbation of existing ones for a period of over 24 hours, at least 30 days after a previous relapse. Disability was assessed using the Expanded Disability Status Scale (EDSS); the six-month disability worsening or improvement were defined as an increase or a decrease by one value in EDSS. The study included 614 patients treated with Aubagio, 782 with Tecfidera, and 2,332 with Gilenya. Patients were followed over a median of 2.5 years. Patients’ characteristics at baseline differed among the three groups. Aubagio-treated patients tended to be older, with longer periods of disease, fewer relapses, and lower EDSS scores compared to the other two groups. Patients treated with Gilenya had higher EDSS and more relapses during the prior year, compared to those treated with Tecfidera. The majority of the patients had been treated with other immunotherapies prior to being given one of these three oral treatments. Results showed that Gilenya-treated patients had significantly lower annualized relapse rates than those treated with Tecfidera (0.20 versus 0.26) or Aubagio (0.18 versus 0.24), while patients taking either Tecfidera or Aubagio had a similar rate. However, during the 2.5-year period analyzed, researchers found no differences in disability accumulation or disability improvement among the three therapies. Regarding treatment persistence, Tecfidera and Aubagio were more likely to be discontinued than Gilenya. Overall, the results suggest that treatment with Gilenya may have a greater impact on relapse frequency in RRMS patients compared to Tecfidera and Aubagio, although the "effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment," researchers said. “Choosing a therapy in individual patients remains a complex task that requires thorough and individualized evaluation of disease prognosis, and the corresponding risks and benefits of the increasing number of available therapies,” they concluded.

Treatment with Ocrevus (ocrelizumab) has superior or comparable effectiveness and a similar safety profile to other available disease-modifying treatments (DMTs) for treating relapsing multiple sclerosis (MS), according to a new review study. The research, “Systematic review and network meta-analysis comparing ocrelizumab with other treatments for…

Autologous hematopoietic stem cell transplant is better than disease-modifying therapies (DMT) at reducing the risk of disease progression in patients with relapsing-remitting multiple sclerosis (RRMS), results from the MIST clinical trial show. The study “Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression…

Tecfidera (dimethyl fumarate) demonstrated strong efficacy in Japanese and other East Asian patients with relapsing-remitting multiple sclerosis (RRMS), a Phase 3 clinical trial shows. These results are consistent with previous clinical trials, which included mostly white MS patients, and show that Tecfidera can also be effective across various other patient demographics. Findings of the trial were reported in the study, “A randomized placebo-controlled trial of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis from East Asia and other countries,” in the journal BMC Neurology. Tecfidera, a delayed-release dimethyl fumarate capsule, marketed by Biogen, is an oral therapy approved in many parts of the world for the treatment of RRMS. In previous Phase 3 clinical studies, DEFINE (NCT00420212), and CONFIRM (NCT00451451), Tecfidera showed substantial effectiveness on clinical and neuroradiological measures in RRMS patients. The study participants were predominantly white (79% in DEFINE and 84% in CONFIRM), and there were 10% or fewer East Asian patients. In general, very little data is available on Tecfidera's effectiveness in East Asian MS patients. In this APEX Part 1 (NCT01838668) trial, researchers from the Kansai Medical University in Japan and Biogen evaluated the safety and efficacy of Tecfidera over 24 weeks (six months) in the treatment of RRMS patients from East Asia and other countries. Participants with active MS between the ages of 18 and 55, with ethnic origins in Japan, South Korea, or Taiwan were included. To compare East Asian and white MS patients, study enrollment was expanded to patients from Eastern Europe (Czech Republic and Poland). In all, the six-month, double-blind, placebo-controlled study recruited 225 patients, 142 of whom were East Asian (63.4%). It was completed by 213 participants. Patients were randomly assigned to receive Tecfidera, (240 mg, twice daily) or a matching placebo for six months. They were assessed at the beginning of the study, at three months, and again at six months. They underwent MRI (magnetic resonance imaging) scans for neurological examination, in addition to routine health checks. The primary objective of the study was the total number of new inflammatory lesions on brain MRI scans from three to six months. Secondary goals included the number of specific new, or newly enlarging T2 hyperintense lesions — lesions reflective of damage to nerve cell connections — from the beginning of the study to six months. Tertiary goals included standard safety measurements, and annualized relapse rate over six months. “We chose radiological measures to serve as primary and secondary endpoints, due to the ability of MRI to detect lesions that might not produce clinical manifestations in the short-term,” the researchers wrote. Results showed that Tecfidera treatment significantly reduced (84%) the total number of new MRI lesions from weeks 12 to 24 (primary objective), compared with placebo — specifically by 85% in the Japanese subgroup, 81% in the total East Asian subgroup, and 87% in the Eastern European subgroup. Regarding the trial's secondary objective, the total number of new MRI lesions from the beginning of the study up to six months was reduced by 75% in the Tecfidera group (78% in the Japanese, 76% in the East Asian, and 73% in the Eastern European subgroups), and the mean number of new/newly enlarging T2 hyperintense lesions was reduced by 63% in the Japanese, and 58% in the East Asian subgroups, compared with placebo. Most patients reported one or more adverse events (77% in the placebo group and 86% in the Tecfidera group). Most adverse events were mild or moderate in severity, and the ones affecting patients taking Tecfidera either related mainly to flushing symptoms or to gastrointestinal problems. The team concluded that the "results suggest that the strong efficacy and favorable benefit-risk profile of [Tecfidera] extends to Japanese and other East Asian patients with MS." The second part of the ongoing clinical trial, APEX Part 2, is an open-label extension trial — where both the researchers and participants know which treatment they are getting — designed to further examine the long-term safety and tolerability of Tecfidera in East Asian MS patients.

Treating a common animal model of multiple sclerosis (MS) with a typhoid vaccine eased disease symptoms by prompting T helper cells to stop production of a pro-inflammatory factor — interleukin (IL)-17 — and by promoting greater numbers of anti-inflammatory  regulatory T-cells, researchers report. Their study, “Targeting prohibitins at the…

Immune cells in the intestine may reduce neuroimflammation in multiple sclerosis (MS) patients, a pre-clinical study suggests. Moreover, the augmented number of these cells was sufficient to suppress brain inflammation in an MS mouse model. The findings were reported in the study “Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via…

Treatment with autologous hematopoietic stem cell transplant (aHSCT) led to a sustained decrease in disability and almost no clinical relapses in patients with relapsing-remitting multiple sclerosis (RRMS) who had failed to respond to prior immunosuppressive therapies, an Australian Phase 2 trial shows. Trial findings were published in the study, “Prospective phase…

Treatment with Ampyra (dalfampridine) for 24 weeks leads to sustained and clinically meaningful improvements in walking ability as reported by multiple sclerosis (MS) patients with gait difficulties, according to a study analyzing results from a Phase 3 trial. The study, “Assessment of Clinically Meaningful Improvements in Self-Reported…

Inactivation of S1PR2, a cell surface protein, helps improve clinical disability and reduce demyelination in a mouse model of experimental autoimmune encephalitis (EAE), a condition similar to multiple sclerosis (MS) in humans, a study shows. This finding suggests that therapies blocking S1PR2 could have the potential to treat MS. The…

Multiple sclerosis (MS) patients who have been relapse-free while using an interferon-beta (IFN-β) therapy but switch to another IFN-β are significantly more like to start experiencing flares than patients who remain on their initial interferon treatment, a real-world study reports. Its results support letting patients remain on a current IFN-β medication…

Tysabri (natalizumab) was found to be superior to interferon beta (IFN-β) in a small, 12-month study with relapsing-remitting multiple sclerosis (RRMS) patients, significantly decreasing their disability levels, its researchers report. A vast majority — 90 percent — of Tysabri-treated patients experienced no relapses during the study period,…

Homotaurine, a compound proven safe for humans in long-term clinical trials, has eased autoimmune responses, brain inflammation, and multiple sclerosis-like symptoms in a mouse model of the disease, a study has found. The findings represent proof-of-principle evidence that homotaurine may represent a new potential class…

Myelin loss might be prevented by astrocytes, a brain cell that regulates myelin’s thickness in coating nerve fibers to support the proper transmission of nerve signals, after astrocytes were seen to block an enzyme called thrombin in a study from the National Institutes of Health (NIH). Its…

Treating relapsing-remitting multiple sclerosis (RRMS) patients with GeNeuro’s investigational compound GNbAC1 lessened brain atrophy and lesion load and suggested myelin preservation, according to results of a Phase 2b study. Importantly, monthly intravenous GNbAC1 administration for 48 weeks also had neuroprotective effects in the study’s inactive population, which refers…