January 15, 2019 News by Jose Marques Lopes, PhD Ocrevus Targets Certain T-Cells, Along with B-Cells, in MS Patients, Study Reports Treatment with a single dose of Ocrevus (ocrelizumab) depleted a subset of immune T-cells within two weeks in patients with relapsing multiple sclerosis (MS) or primary progressive MS (PPMS), according to a study. The study, āOcrelizumab Depletes CD20+Ā T Cells in Multiple Sclerosis Patients,ā was published in the journal Cells. AutoreactiveĀ immune T-cells, which attack the bodyās own tissues, have been regarded as the primary mediator of MS; however, this view has been challenged by the effectiveness of therapies targeting immune B-cells that contain the CD20 cell surface protein in reducing disease activity. One such therapy isĀ Genentechās Ocrevus, an anti-CD20 monoclonal antibody, which was first approved in the U.S. in 2017 for patients with relapsing MS or PPMS. Because CD20 is mainly expressed by B-cell precursors and mature B-cells, Ocrevus is often considered to selectively deplete CD20-containing B-cells. However, CD20 is also expressed by highly activated T-cells with the CD3 protein marker, characterized by the increased production of proinflammatory molecules, or cytokines. These T-cells are found in the blood, cerebrospinal fluid ā the liquid surrounding the brain and spinal cord ā and chronic brain lesions of MS patients, and show an elevated expression of the CD8 and CD45 markers. Off-label use of rituximabĀ (marketed as Rituxan in the U.S. and MabThera in Europe), a lymphoma and rheumatoid arthritis treatmentĀ that also targets CD20, has been associated with the depletion of CD20-containing T-cells in MS patients. Therefore, targeting this T-cell subtype has been hypothesized as an additional mechanism for rituximabās clinical effectiveness. However, scientists did not know whether Ocrevus, which is different from rituximab in terms of CD20 binding and cell toxicity, also depletes CD20-positive T-cells. To address this unknown, a team from Hannover Medical SchoolĀ in Germany analyzed blood samples of MS patients through a technique called multicolor flow cytometry prior to the first dose of Ocrevus and after two weeks, immediately before the second dose. They intended to evaluate the characteristics of the patientsā peripheral blood mononuclear cells, which include T-cells, B-cells, monocytes, and macrophages. A total of 21 patients (13 women) were included, with a median age of 43 years (range 22-65 years). Of the participants, 17 had the relapsing form of the disease forĀ a median of 14.6 years, while four had PPMS for a median of 5.6 years. The analysis found T-cells containing CD20 and CD3 in all patients. These cells accounted for 2.4% of all CD45-expressing lymphocytes ā white blood cells that include T- and B-cells ā and for a significant proportion (18.4%) of all CD20 cells. Evaluation of the cellsā fluorescence intensity revealed that CD20 levels were significantly lower on T-cells than on B-cells also expressing this marker. Treatment with one dose of Ocrevus substantially lowered the levels of CD20-positive T- and B-cells within two weeks, reflected by a frequency of 0.04% and an absolute cell count decrease from 224.9 to 0.57/microliter. āOur results demonstrate that treatment with [Ocrevus] does not exclusively target B-cells, but also CD20+ T-cells, which account for a substantial amount of CD20-expressing cells,ā the researchers wrote. āThese findings suggest that CD20+ T-cells might play a pivotal role in the pathogenesis of MS, and we speculate that depletion of CD3+CD20+ cells by anti-CD20 monoclonal antibodies might contribute to the efficacy of anti-CD20 therapy,ā they added. However, they also emphasized that the findings need to be confirmed in studies with larger groups of MS patients.
January 8, 2019 Columns by Teresa Wright-Johnson Keeping My Eyes on the Prize Welcome to the new year! I am grateful for the opportunity to open my eyes and still have the gift of life. Many did not make it into 2019. Those who have transitioned are remembered with love and respect. Last year, I made a happiness jar. The intent…
January 2, 2019 News by Jose Marques Lopes, PhD Top 10 Multiple Sclerosis Stories of 2018 Multiple Sclerosis News Today brought you daily coverage of key findings, treatment developments, andĀ clinical trials related to multiple sclerosis (MS) throughout 2018. We look forward to reporting more news to patients, family members, and caregivers dealing with MS during 2019. Here are the top 10 most-read articles of…
December 18, 2018 News by Jose Marques Lopes, PhD Pretreating Ocrevus Patients with Multiple Antihistamines and Liquids Lowers Infusion Reactions by 60%, Study Reports PretreatingĀ multiple sclerosisĀ patients withĀ antihistamines more extensively and with hydration can significantly reduce ā by 60% ā the likelihood ofĀ infusion-associated reactions that are the most common side effect of Ocrevus (ocrelizumab) use, a pilot study reported. Data also found that older and male MS patients are less likely to have…
December 12, 2018 News by Alice MelĆ£o, MSc Ocrevus Now Available Through NHS Scotland to Treat RRMS Ocrevus (ocrelizumab, by Genentech) is now available through the National Health System (NHS) of Scotland to treat patients with relapsing-remitting multiple sclerosis (RRMS). The decision by the Scottish Medicines Consortium (SMC) to approve Ocrevus’ inclusion for this patient group follows theĀ recommendationĀ made earlier by the U.K.ās…
December 11, 2018 Columns by Ed Tobias Consensus Lacking on How MS Medications Are Prescribed in the UK Living in the U.S., where disease-modifying therapies (DMTs) seem to be prescribed as a matter of course to people with multiple sclerosis (MS), I was surprised that it doesn’t seem to be the case across the pond in the U.K. An article just published on the Multiple…
November 15, 2018 News by Jose Marques Lopes, PhD Ocrevus Helps Preserve Hand and Arm Function in PPMS Patients, Trial Data Show TreatingĀ primary progressive multiple sclerosis (PPMS) patients with Ocrevus (ocrelizumab) can help to preserve strength and function in their hands and the arms, analysis of data from a Phase 3 trial found. The research, āOcrelizumab reduces progression of upper extremity impairment in patients with primary progressive…
November 7, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 – Better MS Monitoring and Disease Understanding Among Goals of FLOODLIGHT Open, Genentech Director Says The ability to track multiple sclerosis (MS) at any time, gain a more complete picture of each patientās disease course and a better understanding of MS are among the possible benefits of the FLOODLIGHT app, according to Laura Julian, PhD, principal medical science director at Genentech. The company…
November 2, 2018 News by Vijaya Iyer, PhD NICE Postpones Final Opinion on Adding Ocrevus to Public Health System for PPMS Patients in UK A final and weighty opinion regarding whetherĀ Ocrevus (ocrelizumab)Ā will be among treatments available at low or no cost to primary progressive multiple sclerosis (PPMS) patients in England and Wales ā through the National Health Service (NHS) āĀ has been put on hold, according to the Multiple Sclerosis Trust. The…
October 24, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 – Ocrevus Used Early in MS Course Key to Slowing Disability, Genentech Director Says Treating patients withĀ primary progressive or relapsing multiple sclerosis (MS) early with Ocrevus (ocrelizumab) is key to slowing disease progression, according to Hideki Garren, global head of Multiple Sclerosis and Neuroimmunology at Genentech. In an interview withĀ Multiple Sclerosis NewsĀ TodayĀ at the recentĀ 34thĀ congress of the European Committee for Treatment…
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 11, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 – Lower Mortality Rate in US, Sweden for MS Patients Treated With Rituximab, Study Reports Treatment of multiple sclerosis (MS) patients with rituximab leads to lower-than-reported mortality rates, according to a large real-world study in the U.S. and Sweden. The findings also revealed no deaths due to infusion reactions or to systemic inflammation. The study, āMortality rates in large US and…
October 4, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 – Genentech to Present Ocrevus-related MS Studies at Conference Treatment with Ocrevus (ocrelizumab) over five years lessened upper limb disability progression in primary progressive multiple sclerosis (PPMS) patients, reduced relapses and brain disease activity in patients with relapsing MS, and helped achieveĀ no evidence of disease progression (NEDA) in a greater proportion of African-descent patients, compared to treatment…
September 24, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: Treating MS with a Statin, Ocrevus, Remyelination Phase 3 Trial in the UK Soon to Test Statin, Simvastatin, in Slowing SPMS Progression I’ve taken a statin medication for years to keep my cholesterol in check. Now, a study is getting underway to see if one statin pill can also be used to treat MS. It’s particularly…
September 21, 2018 News by Alice MelĆ£o, MSc Ocrevus Climbing as First-line DMT for RRMS Among Neurologists Surveyed in Spherix Report Eighteen months after its entrance into the U.S. market,Ā Genentechās Ocrevus (ocrelizumab) has become the monoclonal antibody of choice to treat patients with multiple sclerosis (MS), according to a survey of nearly 100 neurologists across the U.S. Self-reported use of Ocrevus for theĀ third quarter of 2018 surpassed…
September 13, 2018 News by Jose Marques Lopes, PhD Ocrevus Increases Proportion of PPMS Patients with No Disease Progression or Activity, Phase 3 Trial Shows TreatingĀ primary progressive multiple sclerosisĀ patients with OcrevusĀ (ocrelizumab)Ā led to a three-fold increase in the proportion of those showing no evidence of disease progression and no signs of inflammatory disease activity over more than two years of treatment, results of a Phase 3 trial show, and support new measures that might better capture disability in PPMS patients. The research, āEvaluation of No Evidence of Progression or Active Disease (NEPAD) in Patients With Primary Progressive Multiple Sclerosis in the ORATORIO Trial,ā was published in the journal Annals of Neurology. Measuring disease progression in clinical trials and clinical practice requires reliable and comprehensible measures. Although widely used, the Expanded Disability Status Scale (EDSS, range 0-10) cannot fully capture changes in walking speed and hand or arm function, which are key determinants of overall disability in progressive forms of MS. No evidence of progression (NEP) is a newer measure that reflects the absence of disability progression, including upper limb function and walking speed. Maintaining NEP status means stable disease with no worsening in EDSS, in walking ability (assessed by the Timed 25-Foot Walk (T25FW) test, or the time it takes to walk 25 feet as quickly and safely as possible), and in upper limb function (assessed by the 9-Hole Peg Test (9HPT), a test of arm and hand dexterity). Patients with PPMS have less frequent signs of disease activity, which include relapses and brain lesions (assessed though magnetic resonance imaging or MRI). So scientists proposed a new measure ā called āno evidence of progression or active diseaseā (NEPAD) ā to evaluate both NEP and clinical and MRI measures of active disease. The researchers believe that NEPAD may represent a more sensitive and comprehensive measure of disease control in PPMS patients. The randomized, double-blind ORATORIO Phase 3 trial (NCT01194570) analyzed the efficacy and safety of Ocrevus ā developed byĀ Genentech, part of theĀ RocheĀ group ā in 732 PPMS patients (age range 18ā55). Results showed that Ocrevus treatmentĀ delayed the relative risk of disability progression by 25% compared to placebo, while also reducing the volume of chronic brain lesions and total brain volume loss. As a result, Ocrevus became the first therapy approved by the U.S. Food and Drug Administration and the European Commission for both PPMS and relapsing MS. Now, researchers assessed Ocrevusā effect in PPMS patients included in the Roche-funded ORATORIO study using as trial goals changes in NEP and NEPAD. These people received either 600 mg of Ocrevus or placebo by intravenous (IV) infusion every six months for a minimum of 120 weeks (about 2.3 years). The trialās main goal was time to onset of clinical disability progression (CDP) sustained for at least 12 weeks. CDP was defined as a 1.0 point or greater increase in EDSS score from a baseline (study start) score of 5.5 or less, or a 0.5-point increase from a baseline score greater than 5.5. NEP status, analyzed in 230 placebo- and 461 Ocrevus-treated patients, was defined as no evidence of CDP for 12 weeks, no 20% or more change in hand/arm function as measured by the 9HPT for 12 weeks, and no 20% or more change in walking ability as measured by the T25FW test for 12 weeks.Ā "The 20% cut-off for progression on the T25FW test and the 9HPT has previouslyĀ been shown to be a clinically meaningful magnitude of disease progression," the study noted. In turn, NEPAD ā assessed in 234 placebo- and 465 Ocrevus-treated patients ā included NEP, no brain MRI-measured disease activity, and no relapses.Ā Relapses were defined as new or worsening neurological symptoms attributable to MS lasting longer than 24 hours and preceded by neurological stability for a minimum of 30 days. Brain MRI scans were conducted at baseline, and weeks 24, 48, and 120; new or enlarging T2 lesions and/or T1 enhancing lesions were considered evidence of MRI disease activity (T1 MRI imaging offers information about current disease activity by highlighting areas of active inflammation, while a T2 MRI image provides information about disease burden or lesion load). Overall, the majority of the PPMS patients analyzed experienced clinical disease progression or evidence of disease activity. From baseline to week 120, Ocrevus-treated patients who achieved NEP (42.7% of 461 people) or NEPAD (29.9% of 465) Ā ā no disease activity or progression ā were found to have lower T2 brain lesion volume and a lower EDSS score (lesser disability) compared to those with evidence of MS progression. They also had a slightly superior performance on the 9HPT and the T25FW test. Patients who reached NEPAD also showed fewer T1 lesions than patients with progressing or active disease. Compared to placebo treatment, the proportion of Ocrevus-treated PPMS patients maintaining NEP or NEPAD from baseline to week 120 was higher ā for NEP, 42.7% versus 29.1% in the placebo group; for NEPAD, 29.9% versus 9.4% in the placebo group. These results showed that Ocrevus treatment increased theĀ proportion of PPMS patients with NEPAD throughout the 120 weeks of the study by three-fold. āIn conclusion, ocrelizumab (Ocrevus) increased the proportion of patients with PPMS with no evidence of progression and no clinical and subclinical disease activity compared with placebo,ā the team wrote. āAs such, NEPAD may represent a meaningful and comprehensive disease outcome in patients with PPMS.ā However, data from ORATORIO's open-label extension and real-world data are needed to "determine whether NEPAD maintained throughout 120 weeks will translate intoĀ sustained NEPAD and enhanced protection against accrual of disability in patients with PPMS overĀ the long term," the researchers concluded. Of note, five of the studyās 11 authors are employees and/or shareholders of Roche or Genentech.
September 12, 2018 News by Diogo Pinto NICE Rules Against Bringing Ocrevus into NHS for Primary Progressive Patients in UK The National Institute for Health and Care Excellence, better known as NICE, issued a final decision against includingĀ Ocrevus (ocrelizumab) as a treatment for primary progressive multiple sclerosis (PPMS) in the subsidized public health system for England and Wales. The agency’s “final appraisal,” which mirrors its draft…
September 7, 2018 News by Ana Pena PhD How B-cells Work to Promote T-cell Attacks on Myelin That Lead to MS Detailed in Study B-cells in the immune system play an important role in the unfolding of inflammation and brain lesions in multiple sclerosis (MS), largely by how they influence the actions of another immune system cell, called T-cells, a new study reports. Its findings help explain why therapies…
September 4, 2018 Columns by Ed Tobias Ocrevus Predicted to Be a Billion-dollar Blockbuster Ocrevus, a disease-modifying MS treatment that’s only been on the market a little less than 18 months, appears poised to be a cash cow for its maker, Genentech. The research firm Spherix Global Insights, which analyzes trends in the pharmaceutical industry, predicts that Ocrevus is “poised to…
August 23, 2018 News by Stacy Grieve, PhD Case Study Suggests Need for New Treatment Strategy When Switching from Gilenya to Rituximab Discontinuing Gilenya (fingolimod) treatment and starting on rituximab therapy may be more complicated than originally thought. A new report chronicles the medical journey of a man with multiple sclerosis (MS) treated with these drugs, and proposes a new treatment regimen. Both Gilenya (an approved MS therapy marketed by…
July 30, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: Popular DMTs, Data Analysis Predicts MS, Remyelination Study Oral DMTs Still Common 1st Therapy for New MS Patients but Ocrevus Having Impact, Market Report Says Deciding on what therapy to use is a tough decision for people with MS and their doctors. That’s especially true for someone who is newly diagnosed. Do you go with…
July 13, 2018 Columns by John Connor Steering My Own Boat and Making a Splash The U.K.’s National Health Service (NHS) turned 70 last week. In England, yes, we are mourning our semi-final defeat by Croatia in the World Cup, but to most of us, the NHS is the U.K.’s crowning glory. There are innumerable problems and proposed solutions involving the institution, yet…
July 9, 2018 News by Jose Marques Lopes, PhD NICE Agrees to Add Ocrevus to NHS for RRMS Patients in England and Wales, But Scotland Will Not Relapsing-remitting multiple sclerosis (RRMS) patients with active disease may now be treated with Ocrevus (ocrelizumab, developed byĀ Genentech) within the National Health Service (NHS) ā the subsidized public health system that covers England and Wales. But those in Scotland will not. The National Institute for Health and…
July 3, 2018 News by Vijaya Iyer, PhD NICE Opposes Ocrevus as PPMS Treatment in UK’s Public-funded Health System The National Institute for Health and Care Excellence, known as NICE, has decided against recommending thatĀ Ocrevus be part of public-funded treatments for adults withĀ primary progressive multiple sclerosis (PPMS). The National Health Service (NHS) is the subsidized, publicly funded healthcare system for England, with similar structures…
June 27, 2018 News by Patricia Inacio, PhD After Ocrevus Approval, New Therapies May Become Available for MS, Report Suggests Genentech‘s OcrevusĀ (ocrelizumab),Ā approved in March 2017, has fueled a sea change in the treatment of multiple sclerosis (MS) patients in the U.S., leading to an increased interest in disease-modifying therapies (DMTs) for progressive forms of MS. Now, other potential treatment choices for progressive MS forms will likely…
June 19, 2018 News by Alice MelĆ£o, MSc #EAN2018 ā Ocrevus Lowers Relapse Rates Over Long Term and Better Than Rebif Does, Data Show Long-term treatment with Ocrevus (ocrelizumab) Ā ā as well as switching from Rebif (interferon beta-1a) to Ocrevus ā leads to a significant and sustained reduction in disease activity in relapsing forms of multiple sclerosis (MS). TheseĀ previouslyĀ reportedĀ findingsĀ are further supported by the latest results drawn from pooled data…
June 15, 2018 News by Alice MelĆ£o, MSc #EAN2018 – Ocrevus May Delay Progression to Wheelchair by Up to 7 Years, New Analysis of PPMS Patient Data Shows Treatment with Ocrevus (ocrelizumab) slows disability progression in primary progressive multiple sclerosis (PPMS) in ways that may be of considerable importance to patients ā including the possibility of delaying the need for a wheelchair by up to seven years, according to new data from a Phase 3…
May 21, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: PML Treatment, Gilenya for Kids, Rituximab, and an MS trial that is Enrolling Complications from Gilenya Treatment Managed Successfully, Case Report Says This wasn’t a minor complication. It was a version of PML, a brain disease that can be fatal. PML is also a known side effect of Tysabri, so the report of a successful treatment should be important to…
May 18, 2018 News by Iqra Mumal, MSc Rituximab Seen as Effective and Generally Safe RRMS and PMS Treatment in Study Rituximab is generally safe and effective in treating multiple sclerosis ā with comparable effectiveness to Tysabri (natalizumab) in people with relapsing-remitting forms of the disease, a Swiss study reports. But patients using this therapy can develop recurrent infections, its researchers noted, and doctors should be vigilant. The observational study, ā…
May 14, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: An MS Program for Young Adults, Rituximab Report, Repairing Myelin, and Reducing Inflammation Organizations Join Forces to Launch New Adventure Program for Young MS Patients It seems we too often ignore the needs of younger people who have MS. (I’ve written a couple of columns about this.) This program isn’t a medical approach, but it may serve some other…