Trial results

Blood levels of the nerve damage marker neurofilament light provide a reliable picture of multiple sclerosis activity in both the relapsing-remitting and progressive forms of the disease, a Swedish study reports. The University of Gothenburg researchers also discovered a close link between its levels in blood and spinal fluid. This means the…

Using balloons to enlarge veins so that more blood flows out of the brain and spinal cord fails to help multiple sclerosis patients, according to a clinical trial in Italy. Researchers said the procedure did not improve their functioning or reduce their brain lesions — areas where toxic protein build-ups…

Scientists announced positive and encouraging outcomes from two clinical studies — running as part of the larger Human Vaccines Project — aiming to unravel the mechanisms that underlie our immune system’s ability to fight disease. The results are expected to shed light on unknown aspects of the immune system that scientists at the Human Vaccines Project, a public-private partnership, hope to translate into new trials for diseases linked to the immune system, such as multiple sclerosis. Results from the trials — the Human Immunome Program and the Immunity to Hepatitis B Vaccine study — were recently presented at the World Vaccine and Immunotherapy Congress in San Diego, California. In the ongoing Human Immunome Program, researchers are trying to fill a major knowledge gap in the components and mechanisms of the immune system that allow it to recognize various threats, from viruses, parasites and bacteria to cancer cells. They are using blood samples from healthy people to analyze, at an unprecedented depth, the whole repertoire of genes that make up the surface receptors of immune B- and T-cells, the core cells of the immune system’s defence mechanisms. Results will likely advance how scientists diagnose and treat various diseases, and could prompt the development of new, improved vaccines. "We are studying the immune systems of healthy individuals to identify common elements, which could be important for facilitating new and improved vaccines," James E. Crowe Jr., MD, director of Vanderbilt University Medical Center's Vaccine Center, the leading scientific institution of the Human Immunome Program, said in a press release. Researchers will cross the sequencing information with participants' microbiome composition — the natural community of microbes that reside in an organism and are key for a healthy immune system — and other health and sociodemographic characteristics. "We also plan to expand these studies to complete the catalog across different demographics and geographies and compare healthy subjects with individuals with immune-mediated diseases such as multiple sclerosis, cancer and Alzheimer's, which could also reveal novel diagnostic markers," Crowe said. The second study, the Immunity to Hepatitis B Vaccine trial — currently recruiting participants — aims to understand why some people achieve protection against Hepatitis B after a single vaccine shot, while others require up to three immunizations to acquire full immunity. Understanding why the immune system responds differently in individuals can help researchers improve existing vaccines and potentially lead to one-shot vaccines that provide long-term immunity for all populations. Researchers in this study are analyzing genes belonging to the innate-immune system — a general immune system response, not one tailored to specific threats — and observing that activation of these genes in certain immune cells can predict who will be a responder after a single shot of the Hepatitis B vaccine. Preliminary results of the Immunity to Hepatitis B Vaccine study were delivered in two separate sessions at the congress. One was given by Manish Sadarangani, director of the Vaccine Evaluation Center of the University of British Columbia and BC Children's Hospital Research Institute, and the by and Richard Scheuermann, director of the J. Craig Venter Institute in La Jolla, California. "These preliminary data points toward strategies to understand why some people respond better to vaccines than others," Sadarangani said. "Using single cell analyses, we now have the opportunity to probe vaccine-induced responses more effectively, to not only learn what happens immediately after vaccination, but to monitor responses over time and utilize machine learning to eventually predict the human immune response to vaccines," added Scheuermann. Wayne C. Koff, president and chief executive officer of the Human Vaccines Project, emphasized that researchers are optimistic with the results obtained so far, as they "provide important insights into the scale and complexity of the human immune system and how vaccines confer protective immunity." "With our network of academic and corporate partners, we aim to build on these findings and decode the human immune system, giving the world the tools required to advance the development of future vaccines and therapies to defeat major global diseases," Koff concluded.  

Sweden's Active Biotech said its experimental therapy Laquinimod failed to meet the primary and secondary objectives of Phase 2 clinical trial evaluating the drug's potential to treat primary progressive multiple sclerosis. Laquinimod, also known as Nerventra or ABR-215062, was developed by Active Biotech and Israel's Teva Pharmaceutical Industries. The drug targets inflammation and degeneration in neurological tissue. Preclinical studies using animal models of multiple sclerosis showed that laquinimod regulated inflammatory and immune responses in these animals, reducing disease progression. The ARPEGGIO Phase 2 study aimed to evaluate laquinimod's efficacy, safety and tolerability in PPMS patients. Its primary endpoint was brain atrophy as defined by percent brain volume change. Secondary goals included time to disability progression, change in timed 25-foot walk, and number of new T2 lesions. The multicenter, randomized, double-blind, placebo-controlled trial enrolled 374 individuals. Initially, the study aimed to evaluate two doses of laquinimod — 0.6 and 1.5 mg/day — in PPMS compared to placebo. However, the highest dose was discontinued in January 2016 after some participants reported adverse cardiovascular events. In a Dec. 1 press release, Active Biotech said the lower dose of laquinimod failed to slow both the rate of brain atrophy and disease progression. “There was, however, a reduction in new T2 lesions observed in patients treated with laquinimod 0.6 mg,” said the company's president and CEO, Helén Tuvesson. The trial revealed a similar safety profile to that observed in previous studies in relapsing-remitting MS patients (RRMS). The most common adverse reactions were headache, nasopharyngities, upper respiratory tract infection,and back pain. Results of the ARPEGGIO trial will likely be presented at a future scientific conference and published in a scientific journal. Earlier this year, Active Biotec stopped developing laquinimod as a potential RRMS treatment after a Phase 3 study failed to achieve its primary goal: slowing disease progression. Laquinimod is also being evaluated as a potential therapy for Huntington’s disease in a Phase 2 clinical trial.

Results of a Phase 1 clinical trial in healthy volunteers show that PTL101, an oral cannabidiol compound, is a safe and effectively delivered potential treatment of spasticity in multiple sclerosis (MS) and for conditions like epilepsy, Harvest One Cannabis announced. These findings were published in the journal Clinical Pharmacology in Drug Development, in the study…

Available long-term data on Fampyra (fampridine; 4-aminopyridine) suggest the treatment may improve walking speed in patients with multiple sclerosis (MS) for up to one year, but more research is needed, a French study reports. The study “Multiple Sclerosis and Clinical Gait Analysis before and after Fampridine: A Systematic Review”…

Multiple sclerosis (MS) patients being treated with dronabinol, a cannabinoid, do not show signs of drug abuse or dependency, leading researchers to conclude it has potential to be a long-term and safe treatment option for neuropathic pain. The issue of pain management, specifically central neuropathic pain (CNP), in patients with autoimmune disorders…

Celgene released the results of two Phase 3 trials showing that patients with relapsing multiple sclerosis (MS) who were treated with ozanimod had lower relapse rates and fewer MRI brain lesions compared to those given a current first-line therapy, Avonex (interferon β-1a). These results will be used to support a request…

Research teams from Canada, Portugal and the United States, each with projects focused on predicting and defining characteristics of multiple sclerosis (MS) , will share this year’s 1 million euro ($1,165,700) Grant for Multiple Sclerosis Innovation (GMSI), announced by Merck at the 7th Joint ECTRIMS-ACTRIMS meeting in Paris, France,…

Preliminary data from the Phase 3 EVOLVE-MS-1 trial shows that ALKS 8700 — an investigative therapy developed by Alkermes to treat relapsing forms of multiple sclerosis — has a good safety and tolerability profile. ALKS 8700 is an oral compound. Once inside the body, it is rapidly transformed into the therapeutic compound monomethyl fumarate (MMF). Although similar, this drug candidate was designed to offer features different than those achieved with the commercially available Tecfidera (dimethyl fumarate). Alkermes is currently assessing the safety and efficacy of ALKS 8700 in the EVOLVE-MS program, which includes two Phase 3 clinical trials in patients with relapsing-remitting MS. The EVOLVE-MS-1 is a two-year study being conducted in 107 U.S. and European research sites. It will evaluate the long-term safety of ALKS 8700 in some 930 RRMS patients. Interim data collected during the first month of treating 580 participants showed low incidence of GI adverse events, with no reports of serious events. The most common adverse side effects associated with the treatment were flushing, pruritus and diarrhea. Alkermes, which is based in Ireland, said additional results from the initial three months of treatment further supported the positive safety data of ALKS 8700, with only 2.3 percent of patients reporting serious adverse events and 3.7 percent having to stop treatment. The EVOLVE-MS-2 trial, being conducted at 48 U.S. sites, will compare the safety and efficacy of ALKS 8700 versus Tecfidera in RRMS patients. The study is still recruiting participants. Recent data of EVOLVE-MS-2 was also subject of a poster presentation at the ECTRIMS-ACTRIMS Meeting.

Celgene‘s investigative drug ozanimod has been shown to be more efficient than an intramuscular injection of interferon beta-1a (marketed as Avonex by Biogen) in reducing relapses and disease progression in patients with relapsing multiple sclerosis (MS), according to results of the two-year Phase 3 RADIANCE trial. The findings were…

The Japanese company MediciNova‘s anti-inflammatory agent ibudilast slows multiple sclerosis patients’ brain shrinkage and their loss of the protective myelin coating around nerve cells, a Phase 2 clinical trial shows. Robert J. Fox of Ohio’s Cleveland Clinic Neurological Institute presented the results at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris, Oct. 25-28.

Gilenya (fingolimod) was seen to significantly reduce relapses in children and teenagers with multiple sclerosis (MS), according to data from a Phase 3 study — the first successfully conducted in pediatric patients. Novartis, the therapy’s developer, is preparing to file requests for Gilenya to be approved to…

Lemtrada (alemtuzumab) remains a “game-changer” of a treatment for relapsing multiple sclerosis (MS), with benefits continuing and no new side effects seen in a study of its use that now goes out seven years, Aaron Boster, a neuroimmunologist at Ohio Health, said in an interview at the…

Ozanimod (RPC1063) was seen to lower relapse rates and reduce brain and spinal cord lesions among patients with relapsing multiple sclerosis (MS) participating in a Phase 3 study of the treatment. Giancarlo Comi, from the Vita-Salute San Raffaele University, in Italy, announced the results in a presentation during the ongoing…

After the first round of symptoms, multiple sclerosis can stay mild without causing major problems for decades, a 30-year British study indicates. Karen K. Chung of the University College London Institute of Neurology discussed the findings at the ECTRIMS-ACTRIMS meeting in Paris, which started Oct. 25 and runs until 28. His presentation was titled “Does…

Genentech’s Ocrevus (ocrelizumab) improved the vision of people with relapsing multiple sclerosis better than the widely used therapy interferon beta-1a, according to clinical trial findings presented at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris. Dr. Laura Balcer of the department of neurology at New York University made the presentation, titled “Effect…

While Tysabri (natalizumab) failed to slow worsening disability in people with secondary progressive multiple sclerosis (SPMS) in a Phase 3 trial, researchers now suggest that the treatment did improve walking and arm function in people with advanced disability. Researchers presented new analyses of data from the ASCEND trial (…

Novartis’ Siponimod led to a dramatic drop in the number of inflammation patches in the brains and spinal cords of secondary progressive multiple sclerosis patients, according to a Phase 3 clinical trial. Robert Fox of the Cleveland Clinic’s Mellen Center for Treatment and Research in Multiple Sclerosis presented the findings…

Sanofi Genzyme‘s Lemtrada (alemtuzumab) and Biogen’s Tysabri (natalizumab) are more effective in preventing conversion to secondary progressive multiple sclerosis (SPMS) compared to older injectable drugs, researchers from the University of Cambridge in the U.K. reported at the 7th Joint ECTRIMS-ACTRIMS Meeting Oct. 25-28 in Paris. The…

Mavenclad reduced multiple sclerosis relapses by 79 percent and prevented the development of additional inflammatory lesions in 84 percent of patients with high disease activity, according to presentations Merck KGaA will make in Paris next week. The company will share a host of new data at the 7th Joint ECTRIMS-ACTRIMS…

TG Therapeutics’ ublituximab nearly eradicated a type of immune B-cell believed to be involved in multiple sclerosis, according to a Phase 2 clinical trial. The result was that none of the patients had a relapse during the first six months of the trial, which is continuing, researchers said. In addition, ublituximab reduced the brain and spinal cord lesions of the relapsing MS patients involved in the trial and prevented new ones from forming. The company will present the interim trial results in three poster presentations at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris, Oct. 25-28. Meanwhile, researchers will continue to study the effectiveness of ublituximab, a B-cell-depleting antibody, versus a placebo, for another six months. The trial is being held at several U.S. medical facilities. Participants receive two initial infusions of ublituximab or a placebo on day 1 and 15 during the first 28 days. After this initial period, those in the placebo-group are also given ublituximab and followed for 52 weeks. A key trial finding was that over the initial 24 weeks of the trial, the treatment nearly wiped out a type of B-cell known as CD20 that scientists believe is involved in the development of MS. Only 1 percent of the B-cells remained after a month. While helpful immune T-cell numbers dropped slightly after the first ublituximab infusion, they bounced back quickly. Researchers also reported a reduction in patients' magnetic resonance imaging (MRI) lesions, with no new inflammatory lesions appearing during the six months. So far, none of the trial participants has had a serious adverse event. Most of the adverse events were mild or moderate and related to the infusions. The trial also demonstrated that speeding up infusions did not increase infusion-related reactions. The speed-up results indicated that — if proven effective and safe — ublituximab will be more convenient for patients than B-cell-depleting drugs that require infusions stretching over several hours.

Scientists have been trying to find a way to restore a protective covering around nerve cells whose loss leads to the neuron damage associated with multiple sclerosis. A team at the University of California, San Francisco may have found a way to do it. And perhaps surprisingly, the possible solution…

Two short courses of Lemtrada prevented multiple sclerosis from becoming active and progressing for five years, a study reported. Lemtrada's maker, Sanofi-Genzyme, said the study covered the two-year CARE-MS II Phase 3 clinical trial (NCT00548405) and a long-term extension (NCT00930553) trial of people with relapsing-remitting MS. In addition to demonstrating Lemtrada's effectiveness, the study showed that it was safe, researchers said. The Phase 3 trial participants had had an active disease, with at least two relapses in the two years before the study and an inadequate response to earlier treatment. The trial compared Lemtrada's effectiveness with that of Rebif. The Lemtrada group received 12-mg doses for five consecutive days at the start of the study and three consecutive days a year later. Ninety-three percent of the 435 patients who completed the trial enrolled in the extension, which followed patients for another three years. Remarkably, 60 percent of patients required no additional treatment after the two years of the Phase 3 study. Among the 376 patients who required more treatment, 30 percent had one additional Lemtrada course, 10.4 percent had two, and 1.6 percent had three. A small proportion of patients also received other disease-modifying treatments. The most common reason for additional treatment was relapse. Nevertheless, Lemtrada reduced annualized relapse rates to only 0.18 of patients by the fifth year. In addition, during the five years, 75 percent of patients experienced no worsening of their disability over six-month cycles. And 49 percent of patients' disability improved. Researchers also tracked patients' scores on the NEDA — or No Evidence of Disease Activity — index. The composite measure takes into account relapses, disease activity detected in MRI scans, and disability progression. In year five, 58 percent of patients achieved NEDA, slightly more than the 53 percent in year three. Another important finding was that patients' loss of brain tissue slowed in the first two years, and dropped further during the extension. Researchers also noted that adverse events dropped during the extension trial. Ninety-six percent were mild or moderate, and no patient left the study because of side effects. The rate of infusion-associated reactions was lower in the extension study than in the Phase 3 study. Patients who did have a reaction most often experienced headache, fever, or rash. Infections did not become more common with accumulating Lemtrada doses and, again, were less common in the extension trial. Patients most often developed colds or urinary tract infections. Autoimmune reactions against the thyroid gland were relatively common, however. Thirty-eight percent of patients developed them over the five years. Most were moderate in severity. Four patients developed various types of cancers. Researchers also examined Lemtrada in the CARE-MS I clinical trial and its extension trial. They reported long-term outcomes and safety findings similar to those in the latest study. Overall, the newest results demonstrated that Lemtrada slowed disease progression over five years in relapsing-remitting MS patients who failed to respond to previous therapy.

Non-invasive brain stimulation reduces fatigue in multiple sclerosis patients, concludes a study by researchers at New York University. Fatigue is one the most disabling symptoms of MS, affecting roughly 75 percent of people with the disease. Doctors often prescribe drugs to treat narcolepsy, as well as behavior-based treatments and exercise programs, but their benefits have not been consistent. This led scientists to study a technique of brain stimulation called transcranial direct current stimulation (tDCS), which had shown positive results in earlier neurology studies, including improvements of cognitive symptoms in MS. In tDCS, doctors place electrodes on the scalp via a headset to apply a low-amplitude electrical current at the dorsolateral prefrontal cortex — a brain region believed to play a role in fatigue and cognitive symptoms. The technique has been proven safe and tolerable. The NYU study randomly assigned 27 MS patients to receive either tDCS or placebo. Patients got treatment while playing a cognitive game directed at the brain’s processing speed and working memory. Sessions lasted 20 minutes each and took place five days a week, at patients’ homes. Participants reported their level of fatigue after 20 sessions, using a scale known as the Patient-Reported Outcomes Measurement Information System (PROMIS) that grades fatigue on a score of up to 32. A higher score correlates with more fatigue. The results showed a significant 5.6-point drop with tDCS, compared to a 0.9 point increase in the placebo group. Furthermore, patients may benefit from more sessions, since those who underwent 20 sessions reduced fatigue more than those who did only 10. The study also showed that patients with the most fatigue at baseline saw the biggest improvements. Remarkably, many participants reduced their fatigue to near-normal levels, researchers observed. Further studies are needed to ascertain the precise mechanism behind tDCS. Scientists believe it changes the brain’s excitability, which improves connections and facilitates learning. Meanwhile, the study's authors strongly advise MS patients not to try over-the-counter stimulation technologies outside of a reliable research setting. The research team plans to test tDCS in larger clinical trials for MS-related fatigue, motor and cognitive symptoms. Currently, the Multiple Sclerosis Comprehensive Care Center at NYU Langone Health is the only one in the United States to offer tDCS to MS patients.

Researchers have taken the first steps towards the development of a gene therapy for multiple sclerosis — a treatment that boosted anti-inflammatory immune processes and reversed severe paralysis in mouse models of the disease. The University of Florida Health research team said it was optimistic that the therapy can work…

Two molecules known to regulate cellular signaling contribute to the underlying mechanism of progressive multiple sclerosis, found a recent study conducted by investigators at Oregon Health & Science University and Yale University School of Medicine. These two proteins are related to each other, as they participate in the same cellular signaling process that regulate the immune system's response. Previous studies have blamed them for the worsening of several autoimmune and inflammatory disorders including rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus. The research team found that patients with progressive MS had higher levels of MIF and D-DT proteins than those with the relapsing-remitting form of the disease. In addition, these proteins inflamed the central nervous system, making patients sicker. An analysis of the genes that encode the proteins revealed that higher levels of MIF were linked to the presence of two genetic variants that are more frequent in patients — particularly males — with progressive disease. Researchers confirmed their findings with animal models of MS-like disease that were genetically engineered to lack MIF and D-DT proteins. Taken together, this finding suggests that a simple genetic test could identify patients carrying the MIF genetic susceptibility — and therefore more likely to develop a severe form of MS. This study was partially funded by the National Institutes of Health, the National Multiple Sclerosis Society, the Rocky Mountain MS Center Tissue Bank and the U.S Department of Veterans Affairs.

The Patient-Centered Outcomes Research Institute has awarded $38 million in grants for five projects that compare the effectiveness of different multiple sclerosis treatment strategies. A key aim of the research is to improve knowledge about the therapies to help doctors and patients choose the healthcare option that best meets patients’ needs. The…

MediciNova will present data from its clinical trial of ibudilast (MN-166) in progressive multiple sclerosis (MS) at the upcoming 7th Joint ECTRIMS – ACTRIMS Meeting in Paris. The European and American Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS and ACTRIMS) selected the presentation “…

A Phase 2b trial assessing the experimental retroviral-targeting treatment GNbAC1 in patients with relapsing-remitting multiple sclerosis (RRMS) failed to meet its primary goal of reducing brain lesions and other signs of brain inflammation within six months. But researchers at GeNeuro and Servier — the two European companies that jointly developed the drug…