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."

The question of how quickly to start a disease-modifying therapy (DMT) after a multiple sclerosis (MS) diagnosis is one that I frequently see when I browse online. It goes hand in hand with questions about which DMT is best to start with. There are many things to consider when…

Pendopharm’s Glatect (glatiramer acetate) — a treatment for patients with relapsing-remitting multiple sclerosis (RRMS) — has been added to the public drug plan in the Canadian province of British Columbia, and is now the only glatiramer-based treatment for RRMS patients there using the plan. After Copaxone…

Four disease-modifying therapies (DMTs) for  multiple sclerosis — Avonex, Rebif, Betaferon, and Copaxone — are cost-effective and reduce disease progression in MS patients, especially those with relapsing-remitting disease, according to 10-year, real-world results from U.K.’s MS Risk Sharing Scheme (RSS). But the long-term benefits observed wane over…

Pendopharm’s Glatect (glatiramer acetate injection), a lower cost alternative to Teva’s Copaxone, has been added to the public health plans of five Canadian provinces for patients with…

Oral disease-modifying therapies (DMTs) are the most common first choice of treatment for people newly diagnosed with multiple sclerosis (MS) in the United States, an analysis reports. Antibody-based DMTs like Ocrevus, however, are emerging competitors. Spherix Global Insights, a market research and analysis company, states that 1 in every…

After an agreement to lower their prices, four treatments for relapsing multiple sclerosis — Biogen’s Avonex and Merck KGaA‘s Rebif (both interferon beta-1a), Novartis’ Extavia (interferon beta 1b), and Teva’s Copaxone (glatiramer acetate) — were recommended as cost-effective and long-term therapy options within the National Health Service…

I’m agonizing over an important decision and it’s driving me crazy. I’m usually a quick decision-maker, but this one is tough. I have my analytical hat on, trying to look at my choices from a scientific standpoint. Unfortunately, my anxiety kicks in, and my hat…

Mylan and Mapi Pharma will jointly develop and commercialize Glatiramer Acetate (GA) Depot, an investigative, long-lasting formulation of the commonly used multiple sclerosis (MS) therapy Copaxone (marketed by Teva Phatmaceutical). Under the terms of the partnership, Mylan will acquire global marketing rights for the therapy. The companies are in…

The newest kids on the MS block, disease-modifying therapies (DMT) such as Genentech’s Ocrevus (ocrelizumab) and Sanofi Genzyme’s Lemtrada (alemtuzumab), are attracting a lot of interest these days. But, some DMTs that have been around for more than two decades are still being prescribed by a lot of neurologists.

The U.S. Food and Drug Administration has approved a new dose of Sandoz’s multiple sclerosis therapy Glatopa (glatiramer acetate injection) that is twice as large as the currently authorized one. Regulators’ approval of the 40 mg/mL applies to people with relapsing forms of MS. A mg/mL designation refers to the concentration of…

The Phase 2a trial of GA Depot (glatiramer acetate) for the treatment of primary progressive multiple sclerosis (PPMS) has dosed the first patient, Mapi Pharma recently announced. In the U.S., Copaxone (glatiramer acetate injection, marketed by Teva Pharmaceutical) is the standard therapy for relapsing-remitting multiple sclerosis (RRMS), which is…

Brabio (glatiramer acetate injection), the first generic alternative to Copaxone for relapsing multiple sclerosis (MS) patients, was recently launched in the U.K. at an equivalent higher dose, its maker, Mylan, announced. Similar to Copaxone  — developed by Teva — Brabio is now available at a 40 mg/ml dose. Both medications are…

A British board that recommends what treatments the National Health Service should cover has advised the system to use only Extavia (interferon beta 1b) as a treatment for MS patients who continue to have relapses. Cost was at the heart of the National Institute for Health and Care…

U.S. neurologists are increasingly prescribing Genentech’s Ocrevus (ocrelizumab) to their multiple sclerosis patients, Spherix Global Insights reports. Another good sign for Genentech is that, in just three months, neurologists have increased by 50 percent their estimate of the numbers of relapsing-remitting MS patients who could benefit from Ocrevus.

Synthon’s prefilled syringe with 40 mg/ml of glatiramer acetate — the generic version of Teva Pharmaceutical’s Copaxone 40 mg — has received regulatory clearance in all 28 member states of the European Union (EU) plus Iceland, Liechtenstein and Norway to treat relapsing-remitting multiple sclerosis (RRMS). The low-dose…

The U.S. Food and Drug Administration has approved both lower and higher doses of Mylan’s generic versions of Copaxone (glatiramer acetate) for relapsing multiple sclerosis. It is the first time the agency has authorized a higher-dose generic. Generic versions of the lower dose of 20 mg/mL — intended for…

A European Patent Office decision has opened the door to Synthon providing cheaper generic versions of Teva Pharmaceutical’s Copaxone to people with relapsing multiple sclerosis. What looks like the final hurdle to the generics was cleared when the patent office’s Technical Board of Appeal revoked the last of the patents that Teva…

How many hours do the pharmaceutical companies think we have in our day? I ask because almost all of them have come up with very slick tools to use, particularly mobile apps, to help us improve our daily lives with MS. Not coincidentally, these apps also provide their…

Insurance companies want people to use generics, rather than the more expensive brand-name drugs, right? Maybe not. Because, at least in some cases, they’re doing just the opposite. Some patients are being forced to use brand-name drugs even when those drugs have generic equivalents. Not surprisingly, that means…

First-line treatment with Copaxone (glatiramer acetate) benefits relapsing-remitting multiple sclerosis (RRMS) patients by boosting the number of anti-inflammatory immune cells and restoring the balance of regulatory immune cells, an Italian study shows. The study, “Biological activity of glatiramer acetate on Treg and anti-inflammatory monocytes persists for more than 10…

MS patients who start treatment at a younger age, and whose condition requires hospitalization, are more likely to stop treatment, a Canadian study reports. The research, published in the journal Dovepress, dealt with the main reasons Canadian patients quit first-line injected disease-modifying therapies, or DMTs. It was titled “Persistence to disease-modifying therapies for multiple sclerosis in a Canadian cohort.” DMTs can reduce MS activity, but patients must stick with them in order for them to be effective. “There is currently a paucity of clinical trial data on what happens to individuals when they discontinue DMT," the researchers wrote. "However, recent preliminary evidence from observational studies suggest increased relapses and disability in those who discontinue DMT." Researchers sought to identify MS patients at higher risk of discontinuing treatment. They looked at Manitoba Province's medical database to identify the types of drugs MS patients were taking, and for how long. The analysis covered 721 patients who received injected beta-interferons or Copaxone between 1996 and 2011, and whom doctors followed for at least a year. Teva manufactures Copaxone, whose generic name is glatiramer acetate. The mean age of the patients in the study was 37.6 years, and 74.2 percent were women. Researchers defined a discontinuation of a DMT as a 90-day or longer gap in treatment. A third of the patients were treated with beta-interferon-1b, either Bayer HealthCare's Betaferon/Betaseron or Novartis' Extavia. It was the first such therapy available in Manitoba. Twenty-three percent of patients received beta-interferon-1a, either Biogen's Avonex or Merck's Rebif. And 21 percent received Copaxone. The median time before a patient discontinued a DMT was 4.2 years. Although 62.6 percent of patients discontinued treatment at some point, 57.4 percent either reinitiated it or switched to a different DMT. Patients who were on DMT at least a year were more likely to stay with it than those who stopped in the first year. Importantly, patients who started a DMT at a younger age were more likely to stop taking it than older patients. “Our results are also consistent with previous work examining persistence for other chronic medication classes, including statins, antihypertensives, bisphosphonates, and oral antidiabetic agents, where the risk for discontinuing drugs declined in a linear fashion with age,” the researchers wrote. The team also found that 16 percent of patients had to be hospitalized overnight, with 3 percent of the cases due to MS-related complications. And these hospitalized patients were more likely to stop their DMT treatment earlier, the researchers said. Summing up, the team said: "Subjects who were younger when starting a DMT, had prior MS-related hospitalizations, were more recently diagnosed with MS, or had a greater lag time between their MS diagnosis and DMT initiation were more likely to discontinue therapy." Although "not all of the factors identified with discontinuing DMT" can be modified, "they may help practitioners enhance MS care by identifying individuals who may be at particular risk for DMT discontinuation," the researchers concluded.

Multiple sclerosis patients taking Tecfidera, or dimethyl fumarate, were more productive at work than those on Copaxone or beta-interferon therapies, according to a study. Tecfidera also increased patients’ quality of life, researchers said. The study covered patients with relapsing-remitting multiple sclerosis, or RRMS. The four beta-interferon treatments were Avonex, Betaseron, Rebif,…

Babies of women with relapsing multiple sclerosis (RMS) who receive daily injections of Copaxone (glatiramer acetate) while pregnant carry the same risk of developing birth defects as babies as a whole, according to a study by the therapy’s developer, Teva Pharmaceutical Industries. The findings can help doctors counsel and treat…

Teva Pharmaceutical Industries will discuss two of its multiple sclerosis therapies, one that reduces relapses and one that appears to protect nerve structure, at a premier neurology conference in Boston this month. It will also give presentations at the 2017 Annual Meeting of the American Academy of Neurology on therapies…

(Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with this second of three parts on terms starting with the letter “C.”) When it comes to multiple sclerosis, mastering an understanding of the disease means you need to mind your Ps and Qs, dot your Is, cross your Ts,…

An extension trial assessing generic glatiramer acetate (GTR) treatment in multiple sclerosis (MS) patients found that the formulation is as safe and effective as Copaxone (branded glatiramer acetate), and that switching to GTR is well-tolerated. The findings were in the study, “Switching from branded to generic glatiramer acetate:…

The multiple sclerosis (MS) market shifted during 2016, with oral disease-modifying therapies (DMTs) capturing a greater share and Sanofi-Genzyme’s Aubagio (teriflunomide) being poised for growth, according to a press release from Spherix Global Insights. The conclusions were included in the company’s “RealTime Dynamix: Multiple Sclerosis,” a quarterly report based…

European users of Copaxone (glatiramer acetate injection, Teva Pharmaceutical) to treat relapsing forms of multiple sclerosis (RMS) will no longer see a warning that the drug should not be used during pregnancy. A report assessing this change in the drug’s marketing authorization within the European Union — a process known as…

There might be years-long lags in response to disease-modifying drugs in patients with progressive forms of multiple sclerosis (MS), according to a study that analyzed data from two large clinical trials of progressive MS patients. The study fuels the idea that clinical trials of disease-modifying drugs for progressive MS need…