August 21, 2019 News by Ana Pena PhD Gilenya, Aubagio, Tysabri, Tecfidera Dominate MS Therapy Switches in Europe, Spherix Survey Finds Novartis‘ Gilenya (fingolimod), Sanofi Genzyme‘sĀ Aubagio (teriflunomide), andĀ BiogenāsĀ TysabriĀ (natalizumab) and Tecfidera (dimethyl fumarate) are the top disease-modifying therapies to which patients with multiple sclerosis (MS) have most frequently switched in…
August 1, 2019 News by Ana Pena PhD Oral Vumerity Easier on Gastrointestinal Tract Than Tecfidera, Phase 3 Trial Finds Fewer and less severe gastrointestinal (GI) side effects were evident inĀ relapsing-remitting multiple sclerosis (RRMS) patients taking the investigational oral treatment Vumerity (diroximel fumarate) twice a day compared to those usingĀ Tecfidera (dimethyl fumarate), topline data from the EVOLVE-MS-2 trial show. Vumerity is aĀ fumarate compound being developed…
July 25, 2019 News by Steve Bryson, PhD Tecfidera Up Against Bafiertam in Phase 1 Study of GI Tolerability A first healthy volunteer has enrolled in a randomized, double-blind Phase 1 study to compare the gastrointestinal (GI) tolerability and safety of oral Tecfidera to Bafiertam, an oralĀ bioequivalent in treating relapsing forms of multiple sclerosis (MS),Ā Banner Life Sciences…
July 25, 2019 News by Ana Pena PhD Abundant T-helper Cells Evident in MS Patients May Cause Inflammation, Study Reports Scientists identified and “fingerprinted” a group of T-helper cells that are unusually numerous in the blood and central nervous system of people with relapsing-remitting multiple sclerosis (RRMS), and may be the reason behind the neuroinflammation seen in these patients. This T-cell population carries specific markers involved in the transmission…
May 15, 2019 News by Marisa Wexler, MS #AANAM – Biogen Offers Update on Development Plans for MS Therapies At the 2019 annual meeting of the American Academy of Neurology (AAN),Ā Multiple Sclerosis News TodayĀ sat down with Bernd Kieseier, MD, global head of multiple sclerosis at Biogen, to discuss the company’s portfolio, latest data, and therapeutic development plans in the field of multiple sclerosis (MS). Kieseier said…
May 6, 2019 News by Marisa Wexler, MS #AANAM – IV Therapy May Be More Effective Than Oral Treatment in Younger RRMS Patients, Research Suggests Infusible disease-modifying treatment ā that is, therapies given intravenously ā might have greater benefits for younger people with multiple sclerosis (MS) than oral ones, new research suggests. The research was presented at the ongoing American Academy of Neurology (AAN)’s annual meeting (May 4-10) by Brandi Vollmer,…
April 11, 2019 News by Patricia Inacio, PhD TecfideraĀ Better at Preventing Relapses than Aubagio, Real-world Study Suggests TecfideraĀ (dimethyl fumarate) is more efficient at preventing relapses, and has a lower discontinuation rate than AubagioĀ (teriflunomide), according to a Danish study. The study āComparative effectiveness of teriflunomide and dimethyl fumarate: A nationwide cohort studyā was published in the journal Neurology. Aubagio (marketed byĀ Sanofi Genzyme)Ā and Tecfidera…
March 19, 2019 Columns by Ed Tobias DMT Choice for Your MS Is Your Decision About 15 disease-modifying therapies (DMTs) are available to treat MS these days. So, choosing which to use can be daunting. I’ve been treated with four DMTs since I was first prescribed Avonex (interferon beta-1a) back in 1996. Each time I’ve switched treatments, my neurologist has suggested a number of…
March 11, 2019 News by Jose Marques Lopes, PhD Tecfidera May Work to Lower Relapses by Inducing Epigenetic Changes in T-cells, Study Suggests TreatingĀ 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 ā 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 ofĀ Tecfidera (by Biogen) for people with relapsing-remitting forms of the disease.Ā However, their complete mechanism of action remains unclear. Aiming to address this gap, scientists at theĀ Advanced Science Research Center (ASRC) at The Graduate Center of The City University of New YorkĀ and theĀ 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) ā marketed asĀ CopaxoneĀ byĀ Teva Pharmaceuticals, with generic forms byĀ SandozĀ (asĀ Glatopa) and byĀ Mylan. All patients had stable disease for at least three months, but disease duration was shortest in untreated patients ā 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 typicallyĀ have an activated formĀ 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,Ā treatmentĀ 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 ā the addition of methyl groups ā in T-cells containing CD4, compared to glatiramer acetate. Specifically, this overmethylation was observed in a micro-RNA ā tiny RNA molecules than control gene expression ā 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 beenĀ implicatedĀ in MS. The epigenetic effects of FAEs were subsequently validated by comparing pre- to post-treatment with Tecfidera in seven patients. In turn, in vitroĀ (lab dish) experiments showed that FAEs act specifically on the activation of naĆÆve T-cells ā those able to respond to new pathogens to the immune system ā 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 studyās 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 studyās senior author, concluded:Ā "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."
February 25, 2019 Columns by Ed Tobias MS News that Caught My Eye Last Week: Early DMT Use, Aubagio vs. Tecfidera, Lipoic Acid Study, MS Forums Early Use of High-efficacy DMTs of Long-term Benefit to MS Patients, Real-world Study Reports The question of whether to start treating multiple sclerosis (MS) with an older, less effective disease-modifying therapy (DMT) and then move to a more effective one ā or use a heavy-hitting medication right…
February 22, 2019 News by Jonathan Grinstein Aubagio, Tecfidera Show Comparable Effectiveness in Relapsing MS, Real-world Phase 4 Trial Finds Aubagio (teriflunomide)Ā seems to be superior to Tecfidera (dimethyl fumarate)Ā in slowingĀ whole brain shrinkage in patients withĀ 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,…
February 20, 2019 News by Patricia Inacio, PhD Early Use of High-efficacy DMTs of Long-term Benefit to MS Patients, Real-world Study Reports 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, āClinical Outcomes of Escalation vs Early Intensive Disease-Modifying Therapy in Patients With Multiple Sclerosis,ā was published in the journalĀ …
January 29, 2019 News by Patricia Inacio, PhD Gilenya Better at Lowering Relapse Rate than Tecfidera or Aubagio, Study Suggests Gilenya is linked to significantly lower annualized relapse rates in relapsing-remitting multiple sclerosis (RRMS) patients compared to Tecfidera orĀ Aubagio, a study suggests. All three therapies showed similar effects on disability outcomes. Oral immunotherapies ā including Novartisā Gilenya, Biogenās Tecfidera, and Sanofi Genzymeās Aubagio ā 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 therapyās 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. Patientsā 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. āChoosing 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,ā they concluded.
January 17, 2019 News by Jose Marques Lopes, PhD Fewer RRMS Patients Relapse, Discontinue Treatment with Gilenya, Study Finds Relapsing-remitting multiple sclerosis (RRMS) patients on Gilenya (fingolimod) have fewer relapses and stay on treatment longer than those takingĀ Tecfidera (dimethyl fumarate) or Aubagio (teriflunomide), according to a new study. The research, āComparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis,ā was published…
January 4, 2019 News by Alberto Molano, PhD Bafiertam, a Bioequivalent of Tecfidera, Receives Tentative OK from FDA for RRMS Banner Life SciencesĀ has received tentative approval from the U.S. Food and Drug Administration (FDA) for its new drug application (NDA) for Bafiertam (monomethyl fumarate), a novel bioequivalent of Biogenās Tecfidera (dimethyl fumarate) for the treatment of relapsing-remitting multiple sclerosis (RRMS). Final approval is expected no later than…
December 18, 2018 News by Alice MelĆ£o, MSc FDA Asked to Approve Diroximel Fumarate as Oral Treatment for Relapsing MS AlkermesĀ filed a request for the approval of diroximel fumarate (BIIB098) to treatĀ relapsing forms of multiple sclerosis (MS) with the U.S. Food and Drug Administration (FDA). If approved, diroximel fumarate will be marketed by BiogenĀ in the U.S., likely under the brand name Vumerity. Alkermes and Biogen are working…
October 17, 2018 News by Ana Pena PhD #ECTRIMS2018 – Evobrutinib Seen to Lower Active Brain Lesions in Phase 2 Trial Merck KGaA announced that evobrutinib, its oral candidate for relapsing multiple sclerosis (MS), was able to safely and significantly reduce active brain lesions overĀ 24 weeks of treatment, according to results of a Phase 2 study sponsored by the company.
October 16, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 – Two European Studies Compare Tecfidera, Aubagio Effectiveness Treatment of relapsing-remitting multiple sclerosis (RRMS) patients with Tecfidera (dimethyl fumarate)Ā is associated with fewer new brain lesions at two years, lower relapse rates, increased time to first relapse, and reduced treatment discontinuation than with Aubagio (teriflunomide), according to a nationwide study from France and a real-world, population-based…
October 15, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 – Plasma Neurofilament Light Levels Linked to Treatment Effects in RRMS, Study Finds Levels of proposed biomarker neurofilament light chain (NfL) are associated with therapeutic effects of disease-modifying treatments (DMTs) inĀ relapsing-remitting multiple sclerosisĀ (RRMS) patients, according to a real-world study. Study findings also revealed that treatment with either Lemtrada (alemtuzumab, marketed byĀ Sanofi Genzyme),Ā Gilenya (fingolimod, marketed by Novartis), Tecfidera (dimethyl fumarate, marketed…
October 5, 2018 Columns by Ed Tobias Could Government Probe Threaten Pharma Patient Assistance Programs? Many of us have received help to pay for our MS medications. Now there’s a chance that assistance could be threatened. A recent article in the The Wall Street Journal reports that U.S. government prosecutors are looking into whether some pharmaceutical companies’ patient assistance programs are on the wrong…
September 12, 2018 Columns by Mike Knight Out on a Stim: My FES Journey Comes to an End (Part 3) Third in a series. Read parts one and two. In March 2018, I began a personal research project ā quest if you will ā to assess how functional electrical stimulation (FES) devices might help me deal with the foot drop in my…
August 30, 2018 News by Marta Figueiredo, PhD Tecfidera, Gilenya Equally Effective, But More MS Patients Stop Tecfidera, Real-World Study Shows TecfideraĀ (dimethyl fumarate) and GilenyaĀ (fingolimod) are equally effective in treating multiple sclerosis (MS),Ā but Tecfidera shows higher rates of discontinuation, according to a real-world study. The study, āDiscontinuation and comparative effectiveness of dimethyl fumarate and fingolimod in 2 centers,ā was published in the journal Neurology Clinical…
June 13, 2018 News by Vijaya Iyer, PhD Effectiveness of Gilenya and Tecfidera Compared in Real-World Study in Italy Gilenya (fingolimod) and Tecfidera (dimethyl fumarate) are equally effective as first-line treatments in people with relapsing-remittingĀ multiple sclerosis (RRMS), but Gilenya may be of slightly more benefit to those who switch from a previous injectable therapy, according to a real-world study of patients in Italy. The study, “…
June 11, 2018 News by Patricia Silva, PhD BIIB098 Showing Ability in Studies To Be Easier on GI Tract Than Tecfidera, Earning Alkermes $50M from Biogen Alkermes announced that it has received a $50 million payment from Biogen after a review of preliminary data related to theĀ gastrointestinal tolerability ofĀ BIIB098 (diroximel fumarate), now in pivotal clinical studies as a possible treatment for relapsing forms of multiple sclerosis (MS). BIIB098, formerly known as ALKS 8700…
April 25, 2018 News by Patricia Inacio, PhD #AAN2018 ā ALKS 8700Ā Shows Promise as RRMS Therapy, Phase 3 Trial Interim Results Suggest A one-year analysis of the ongoing Phase 3 EVOLVE-MS-1 trial of ALKS 8700Ā as a therapy for relapsing remitting multiple sclerosis (RRMS) supports the experimental therapy’s effectiveness, with the treatment significantly reducing the number of MS lesions. Interim results from the trial were presented Tuesday at the…
April 24, 2018 News by Marta Figueiredo, PhD Compound Produced by Immune Cells May Hold Promise for Multiple Sclerosis A compound produced by immune cells is able to treat psoriasis ā a skin disorder ā in mice, and may be effective against other autoimmune diseases, such as multiple sclerosis, according to a recent study. The study, āElectrophilic properties of itaconate and derivatives regulate the IĪŗBĪ¶āATF3 inflammatory…
March 9, 2018 News by Patricia Inacio, PhD Merck’s MS Therapy Evobrutinib Significantly Reduces Brain Lesions, Phase 2 Trial Shows Merck KGaA’sĀ evobrutinib led to significant reductions in relapsing multiple sclerosis patients’ brain and spinal cord lesions, compared with a placebo, a Phase 2b clinical trial showed. Researchers measured the number of lesions at weeks 12, 16, 20 and 24. Evobrutinib, also known as M2951, is an oral inhibitor of…
February 8, 2018 Columns by Tamara Sellman The MS Alphabet: Plaquenil, PML, Prevalence, and Other ‘P’ Words (Part 6 of 7) Editorās note: Tamara Sellman continues her occasional series on the “MS alphabet” with this column referencing terms starting with the letter “P.” This post comes sixth in a series of seven. Symptoms of MS Progressive multifocal leukoencephalopathy (PML) Though progressive multifocal leukoencephalopathy (PML) isnāt an actual symptom of MS,…
January 22, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: Ocrevus in the EU, Salt and Cognitive Problems, Searching for Myelin, Tecfidera Tolerance European Commission Approves Ocrevus to Treat RRMS, PPMS Throughout EU This is a biggie. It’s been nearly a year since the FDA approved the use of Ocrevus here in the U.S. Finally, it’s been given the green light in Europe. Canada, Australia, Switzerland, and various countries in…
January 17, 2018 News by Ana Pena PhD Majority of RRMS Patients in Swedish Study Seen to Stop Using Tecfidera Within 2 Years A majority of relapsing-remitting multiple sclerosis (RRMS) patients at a Swedish clinic who initiated treatment with Tecfidera (dimethyl fumarate; DMF) either stopped or switched to another therapy within two years, a study reports. Researchers in the observational study were not able to determine exact reasons for discontinuation. But, they wrote,…