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.
PPMS
Europeans with relapsing multiple sclerosis (MS) and early primary progressive MS are one step closer to accessing Ocrevus, now that the European Medicines Agency has urged the European Union to approve the therapy. The positive opinion — announced in a press release issued Nov. 10 by the EMA’s Committee for Medicinal Products for Human Use — is an intermediary step required in the regulatory pathway to allow patient access to a new drug. The European Commission will now make a final decision on whether Ocrevus should be granted marketing authorization in all 28 EU member states. This decision will take the CHMP recommendation into consideration. If approved, Ocrevus will become the first disease-modifying medicine available throughout Europe for patients with PPMS. Once this happens, any decisions on price or insurance reimbursements will be the responsibility of each member state. Ocrevus won U.S. approval earlier this year. It was also recently approved in Switzerland for both relapsing MS and PPMS. Ocrevus is an anti-CD20 antibody developed by Genentech, a division of Roche. It blocks immune B-cells, preventing them from attacking nerve cells and their myelin protective sheath, as well as inhibiting other pro-inflammatory immune signals involved in MS. CHMP based its positive recommendation on data from three pivotal Phase 3 clinical trials: the OPERA I and II trials in relapsing MS patients, and the ORATORIO trial in PPMS patients. Results from the OPERA clinical studies demonstrated that treatment with Ocrevus for up to 96 weeks could reduce the annualized relapse rate by 46.4 percent compared with EMD Serono’s approved drug Rebif (interferon beta-1a) in relapsing MS patients. The ORATORIO trial showed that Ocrevus could reduce by 24 percent the risk of 12-week confirmed disability progression compared to placebo in PPMS patients. Data from the trial further supported the drug's therapeutic benefit in early-stage PPMS patients. Additional studies are warranted to better evaluate the therapeutic potential of Ocrevus for patients with more advanced stages of the disease. The most common treatment-associated adverse effects reported wee infusion-related reactions and infections.
In the future, a blood test may make diagnosing multiple sclerosis (MS) much easier, thanks to newly identified biomarker patterns that distinguish between MS patients and healthy people. The test could also correctly detect primary progressive MS (PPMS) in patients who also had relapsing-remitting disease (RRMS). Australian researchers suggest that…
Genentech will present a host of new information on its multiple sclerosis treatment Ocrevus and lessons its scientists have learned about the disease at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris, Oct. 25–28. The presentations will offer new insights into the therapy's mechanisms, safety and effectiveness in people with the primary progressive and relapsing forms of MS. They will also look at new ways to track MS, including additional biomarker possibilities. MS experts say the joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) is one of the largest global congregations of scientists working on the disease. The information Genentech plans to present will demonstrate "the commitment of our scientists and research partners to advance understanding of MS progression through ongoing analyses of the Ocrevus Phase 3 clinical trials,” Dr. Sandra Horning, the company's chief medical officer and head of its Global Product Development arm, said in a press release. Genentech, which is part of the Roche group, said the 18 presentations will represent the largest body of evidence ever presented on Ocrevus. The discussions will reinforce the therapy's favorable benefit-risk profile, Genentech added. Two presentations will cover new ways that doctors can look for signs of disease activity that can lead to disability. One yardstick is called progression independent of relapse activity, or PIRA. Another is tracking slowly evolving lesions. Genentech researchers came up with the approaches when they analyzed a subgroup of patients in the OPERA I and OPERA II Phase 3 clincal trials, whose aim was to evaluate Ocrevus as a treatment for relapsing MS. The patients' disease progressed even though they had no relapses, researchers said. The team will also discuss how Ocrevus affected these patients' disease. Another presentation will cover long-term follow-up data from an extension of the ORATORIO Phase 3 clinical trial (NCT01194570), which dealt with Ocrevus' ability to treat primary progressive MS. It will look at how well Ocrevus slowed the progression of patients' disability. Updated information on Ocrevus’ safety — based on open-label extension studies — will be another component of the presentations. So far, researchers have detected no new safety issues. Genentech will also discuss a new way of using conventional magnetic resonance imaging (MRI) to identify and track slowly evolving lesions. The company's scientists think that tracking the lesions may be a good way to measure chronic disease activity. This would contrast with tracking ordinary MS lesions, which are biomarkers of acute — as opposed to chronic — disease activity. In addition to "two new potential markers of underlying disease activity and their impact on disease progression, we hope to bring new tools to the MS community to better understand and manage the disease,” Horning said. One tool, which Genentech has begun testing in clinical trials, is gathering patient information with sensors connected to a smartphone. Researchers are comparing the information obtained in the FLOODLIGHT study with what physicians record during patient visits. The research team believes the FLOODLIGHT method may be be able to detect subtle changes better. This could make it a better predictor of disease activity and long-term patient outcomes. In addition to the presentations, Genentech will sponsor two symposia at the meeting that will discuss how MS progresses, features of the chronic version of the disease, and the link between inflammation and the progression of MS. The U.S. Food and Drug Administration approved Ocrevus in March 2017.
Patients with primary progressive multiple sclerosis have more severe cognitive impairment than those with relapsing-remitting multiple sclerosis, according to a German study that analyzed published data on the topic. PPMS patients did especially poorly on verbal learning and verbal memory tests, said the study, which suggested that PPMS patients need disease management that specifically focuses on their cognitive difficulties, which do not necessarily correlate with the degree of overall disability. The study gathered data from 47 previously published studies in an attempt to analyze potential differences in cognitive performance between patients with RRMS and PPMS. These studies included 4,460 patients — 3,456 with RRMS and 1,004 with PPMS — and plenty of information about patient and disease features. This allowed researchers to perform a meta-analysis of pooled data from various studies, that is considered the highest level of scientific evidence. Researchers noted that PPMS patients performed worse on cognitive tests, both when considering global scores and tests of specific cognitive domains. Yet both groups scored similarly in levels of anxiety, depression and fatigue. Using statistical analyses, the research team found that differences in sex, education, disease duration, manual dexterity and fatigue could not explain the poorer test results among PPMS patients. On the other hand, PPMS patients were, on average, older than those with relapsing disease, and the team found that this difference accounted for poorer test results in cognitive tests of processing speed and working memory. Yet differences in other cognitive aspects also remained when researchers took age into account. Differences in disability, measured by the Expanded Disability Status Scale, could also not explain why PPMS patients performed worse on the cognitive tests. A detailed look revealed that the largest differences between RRMS and PPMS patients were in verbal learning and verbal memory, along with the age-associated difference in processing speed. Depression and anxiety also brought down processing speed, researchers said, even though the two groups did not differ in their levels of anxiety and depression. The data shows that cognitive impairment in MS is not directly related to the course of the disease. Research may explain differences in other factors including genetics, the degree of brain tissue loss and medications.
Five clinics in the Washington area that specialize in administering intravenous and injected treatments to people with chronic diseases are now offering the new multiple sclerosis therapy Ocrevus (ocrelizumab). Arise Infusion Therapy Services said its staff is helping patients manage the authorization process that many insurers require before agreeing to cover…
Problems with sense of smell are more frequent and severe in patients with primary progressive multiple sclerosis (PPMS) than in those with relapsing-remitting multiple sclerosis (RRMS), a study reports. The research, “Olfactory dysfunction in patients with primary progressive MS,” was published in the journal Neurology: Neuroimmunology and Neuroinflammation. A distinguishing feature of RRMS, the most common form of the disease, is attacks of new or increasing neurologic symptoms, such as movement disorders, and then recovery periods. About 15 percent of patients have the primary progressive form, or PPMS. Its main feature is gradually increasing neurologic disability without recovery periods. Some scientists believe PPMS is a less inflammatory course of MS. The differences in the processes that underlie each form are not well understood, however. Several researchers think that studying differences in the two groups' ability to smell — or olfactory dysfunction — could shed light on these underlying processes. Autopsies of MS patients in one study showed that 71 percent had experienced demyelination, or loss of neurons, in the brain's olfactory pathway. The processes that led to this dysfunction were unclear, however. Researchers decided to test the hypothesis that olfactory impairment is more pronounced in patients with PPMS than RRMS. The team examined 32 patients with PPMS, 32 with RRMS, and 32 healthy controls. The yardstick they used to evaluate sense of smell was the olfactory Threshold Discrimination Identification (TDI) Test. It involves patients smelling 48 sniffin' sticks. In addition to an overall TDI, there were subscores on olfactory threshold, odor identification and odor discrimination. Olfactory threshold refers to the lowest concentration of an odor that a person can detect. Researchers found olfactory dysfunction in 27, or 84 percent, of the PPMS patients; 10, or 31 percent, of the RRMS patients; and 1, or 3 percent, of the healthy controls. The TDI score and all subscores were significantly worse in patients with PPMS than in the controls, when considering patients of similar age and the same sex. The TDI score was also worse in PPMS patients than in the RRMS group, after adjusting for age, sex, MS disability level, the length of time patients had the disease, and patients' ability to identify and discriminate among odors. Researchers acknowledged limitations to the study. One was the small size of the groups in the research. Another was not using magnetic resonance imaging, or MRI, to measure olfactory pathway deterioration. Comparing the brain's olfactory pathway region with other brain regions in both the RRMS and PPMS groups could have shed light on the processes underlying the olfactory dysfunction differences between the two, researchers said. “The findings suggest that olfactory dysfunction might be a surrogate of neurodegeneration in these patients," the researchers wrote. "Studies correlating olfactory function with radiologic and clinical markers of disease progression would be of interest.”
Ocrevus (ocrelizumab) significantly reduces disease activity and disability progression in patients with relapsing multiple sclerosis (MS) and primary progressive MS (PPMS), according to results of post-hoc analyses of Genentech’s Phase 3 clinical trial program assessing the drug.
Cigarette smoking is certainly no good for you, but it may not necessarily make your primary progressive multiple sclerosis (PPMS) worse, a new study finds. The study, “Smoking does not influence disability accumulation in primary progressive multiple sclerosis,” appeared in the European Journal of Neurology. It contradicts what was…
An investigational treatment called ATA188 that wipes out B-cells targeting the Epstein-Barr virus (EBV) has shown promise as a multiple sclerosis treatment, a Phase 1 clinical trial involving a small patient group indicates. The trial, conducted in Australia, covered six people with primary or secondary progressive MS. B-cells are a…
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…
A 60-year longitudinal multiple sclerosis (MS) study in a Norwegian cohort analyzing life expectancy, survival and mortality concluded that MS patients live shorter lives and have higher mortality than the general population. The report, “Survival and cause of death in multiple sclerosis: a 60-year longitudinal population study,”…
Brain stem cells from primary progressive multiple sclerosis (PPMS) patients lack the ability to repair brain damage and to trigger the maturation of protective myelin-producing cells, a surprising study with far-reaching implications indicates. The study also showed that stem cells from individual patients reacted differently to compounds developed to trigger…
Diplomat Pharmacy, the largest independent specialty pharmacy in the U.S., has been selected to dispense Ocrevus (ocrelizumab), a limited-distribution drug, to people with relapsing and primary progressive multiple sclerosis. Ocrevus was approved by the U.S. Food and Drug Administration on March 28, becoming the first therapy approved for both RMS and…
At long last, and for the first time in medical history, people with both relapsing and primary progressive forms of multiple sclerosis have reason to celebrate. The U.S. Food and Drug Administration (FDA) today approved Ocrevus (ocrelizumab) as a disease-modifying therapy for both forms of MS, a chronic autoimmune disease.
Twenty years ago, the idea that B-cell depletion could treat multiple sclerosis would have been greeted with a hearty laugh by any well-respected neurologist or MS researcher — or perhaps a scoff. But times change and research advances. Today, a medicine that gets rid of certain B-cells may be the most powerful drug yet developed against…
There is now less than a month until the U.S. Food and Drug Administration (FDA) is expected to approve Ocrevus, generic name ocrelizumab, for use as a therapy for multiple sclerosis. Clinical trials have shown Genentech’s drug to be a promising therapy for relapsing MS and, significantly,…
‘Ocrevus Has the Potential to Change How MS Is Treated,’ Genentech’s Peter Chin Says in Interview
March 28, at the latest, may be a historic date for the multiple sclerosis (MS) community — patients, families, caregivers, researchers, and physicians alike. The U.S. Food and Drug Administration (FDA) will have its say about the marketing approval for Ocrevus (ocrelizumab). The drug will be the first to offer benefit to…
Genentech’s Ocrevus (ocrelizumab) increased the proportion of patients with no evidence of progression (NEP) in the recently concluded ORATORIO Phase 3 clinical trial in patients with primary progressive multiple sclerosis (PPMS). The evaluation of NEP — a combined measure of three disability assessments — was a secondary exploratory endpoint of…
A number of important discoveries, therapeutic developments, and events related to multiple sclerosis (MS) were reported daily by Multiple Sclerosis News Today throughout 2016. Now that the year is over, it is time to briefly review the articles that appealed most to our readers. Here are the top 10 most-read articles of 2016, with…
Recently published data from three Phase 3 trials of Ocrevus (ocrelizumab) show that the investigational drug does what no other therapy has achieved so far — working to prevent disease in both relapsing and primary progressive (PP) forms of multiple sclerosis (MS). Publications in the New England Journal…
The U.S. Food and Drug Administration recently extended until the end of March its review of the Biologics License Application (BLA) for Ocrevus (ocrelizumab). The application was submitted by Roche, requesting FDA approval for Ocrevus as a treatment for patients with relapsing-remitting multiple sclerosis (RRMS) and — for a first…
The Institute for Clinical and Economic Review (ICER) has released a Draft Evidence Report evaluating the comparative clinical effectiveness and value of disease-modifying therapies (DMTs) for patients with relapsing-remitting and primary-progressive forms of multiple sclerosis (MS). Through Dec. 21, patients, the public, and other stakeholders can access the 82-page report and…
Discovery MS, a nonprofit research initiative based at the David H. Murdock Research Institute (DHMRI) in North Carolina, had its official launch recently, and announced a series of research projects into multiple sclerosis (MS). The initiative uses private funding to advance research aiming to develop new prognostic and diagnostic tools for MS.
Long-term observations together with mathematical modeling present a way of predicting the likely disability trajectory of multiple sclerosis (MS) patients. The approach was outlined in a presentation, titled “Long-term disability trajectories in primary progressive MS patients – a latent class growth analysis,” given at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in London…
Positive new data from Phase 3 clinical trials assessing Ocrevus (ocrelizumab) as a treatment for both relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) were recently announced by Roche, the company responsible for marketing and developing this investigational therapy. The results are being presented at the 32nd Congress of the…
I knew of no available treatment options for my Primary Progressive MS, so when I heard about the pure High Dose Biotin Protocol I jumped on board! The protocol, created by MedDay in France, revolves around the vitamin Biotin (aka, vitamin B7 or H). It is recommended that the…
Even before my 2010 Primary Progressive MS diagnosis, I was influenced by my inner voice. Way too many times I’ve given into my insecurities and visions of all the terrible scenarios that could occur. Everyone has that little voice. The one that will whisper, “you can’t do that,” or, “why bother?…
Editor’s Note: Debi Wilson’s column “Faith of the Mustard Seed” explores a range of important topics that relate directly to the patient experience. In her debut article, she discusses her own experiences with neurologists, and encourages MS to not settle on a specialist until they feel as though their…
In addition to a new study sponsored by Genentech to test the experimental MS therapy Ocrevus (ocrelizumab) in RMS patients who have had a sub-optimal response to previous disease modifying therapies, the company is also currently recruiting patients with relapsing multiple sclerosis to understand the therapy’s mechanism of action and B-cell biology…