The FDA has approved Ocrevus tonight for primary progressive and relapsing forms of multiple sclerosis. The approval is a major breakthrough since no treatments have previously been approved for primary progressive multiple sclerosis. This monoclonal antibody treatment works by depleted B cells, a type of immune cell. Ocrevus is given intravenously with half given the first day and a second half given 2 weeks later, followed by a single infusion every 6 months.
In 2 relapsing multiple sclerosis trials (OPERA I and II), patients treated with Ocrevus had 46 to 47% less relapses than Rebif. In addition, patients treated with Ocrevus were 40% less likely to progress in disability compared to Rebif treated patients. On MRI scans, the average number of active contrast-enhancing lesions were 94-95% less with Ocrevus treatment than Rebif. In a primary progressive trial (ORATORIO) of 732 patients, treatment with Ocrevus reduced risk of disability progression by 24% compared to placebo treatment. A 29% benefit was also seen on the time to walk 25 feet.
The most common side effects in clinical trials were infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity. Although PML (progressive multifocal leukoencephalopathy) did not occur in Ocrevus clinical trials, this brain infection, which is potentially fatal, has occurred rarely with another B-cell depleting treatment. Other serious infections including reactivation of a Hepatitis B infection are risks. A higher rate of malignancies was seen on ocrelizumab than placebo or Rebif so possible risk of treatment with Ocrevus.
You’re invited to our free annual program to hear about the latest in multiple sclerosis treatments including new exciting results in progressive disease. Groundbreaking research from the world’s largest annual international MS conference in mid September will be presented. An array of topics will be addressed including bone marrow transplant, stem cells and myelin repair. Question and answer session will follow. Light refreshments will be served.
Speakers: Barry Singer, MD; Mark Tullman, MD; Melanie Huff, BSN, RN.
THURSDAY October 6, 2016 6:30 to 8:30 PM, St. Louis Frontenac Hilton, 1335 South Lindbergh
REGISTER: 314-996-LIFE (314-996-5433) or 800-392-0936.
Zinbryta is an antibody therapy that binds onto a receptor (interleukin-2) on the surface of T immune cells. The SELECT trial studied 621 relapsing-remitting multiple sclerosis patients randomized to placebo and Zinbryta 150 mg [daclizumab high-yield process (HYP)] injected under skin every 4 weeks for 1 year. Relapses were reduced 54% for patients on Zinbryta compared to placebo. Zinbryta treatment was associated with 57% less disability progression compared to placebo.
In the DECIDE study of 1841 relapsing-remitting multiple sclerosis patients, Zinbryta under skin every 4 weeks was directly compared to Avonex weekly injections into muscle over 96 to 144 weeks of treatment. Patients on Zinbryta had 45% less relapses than Avonex. Less MRI activity was seen in people treated with Zinbryta (54% reduction on new or newly enlarging T2 lesions and 60% reduction on contrast-enhancing lesions).
Zinbryta can cause severe liver injury including liver failure and autoimmune hepatitis. Liver blood tests are required monthly and up to 6 months after last dose. Other immune-mediated disorders can occur including skin reactions, enlarge lymph nodes, and colon inflammation (colitis). These conditions may require treatment with steroids or immunosuppressive medication.
Most common side effects from Zinbryta (compared to Avonex) included upper respiratory infections, rash (37% of patients) and enlarged lymph nodes. Before starting Zinbryta, testing should be performed for viral hepatitis B and C as well as tuberculosis. Because of its safety profile, Zinbryta should generally be reserved for patients who have had inadequate response to 2 or more MS treatments.
Multiple sclerosis genetically clusters with other autoimmune diseases, especially Crohn’s and Celiac diseases. Genetic research shows that T regulatory cells and B cells (both types of a white blood cells called lymphocytes) are important in multiple sclerosis. High salt diet may cause immune dysregulation, leading to increased inflammation.
Remyelination (recoating the nerves with myelin) was a focus of a great 4 hour afternoon session. Approximately 5% of the cells in the brain are immature cells called OPCs (oligodendrocyte precursor cells) that potentially could make myelin. These cells may be important for learning and not just remyelination. Why does remyelination fail in MS? May be due to factors that block remyelination, damage to the nerve (axon section) itself, and the timing of repair.
To test compounds for myelin repair, remyelination can actually be visualized in translucent Zebra fish. Micropillars of immature myelin-making cells is another interesting approach to screen for effective compounds to increase new myelin production. The technique involves upside down cones coated with OPCs. Clemastine and benzatropine compounds worked in this model. To see if remyelination works in humans, imaging techniques being examined include PET with MRI scans, myelin water imaging and magnetic transference ratio analyses.
More data was presented on high efficacy treatments. In the OPERA trials of ocrelizumab (Orevus), 48% of patients had no evidence of disease activity (called NEDA) over 2 years in comparison to 25-29% of Rebif patients. NEDA means no relapses, no change in disability and no new MRI activity. Alemtuzumab (Lemtrada) was shown to very effective over 5 years in highly active MS patients whether previously treated with MS treatments or new to MS treatment.
Barry Singer, MD, our center’s director, continues to work hard to further our understanding of multiple sclerosis and advance treatment. He presented scientific posters at the Academy of Neurology Meeting in Vancouver in April 2016. Topics were the efficacy of using Lemtrada (alemtuzumab) in patients with highly active multiple sclerosis and rapid benefits of Gilenya (fingolimod) in relapsing forms of multiple sclerosis.
Dr. Singer also just published a chapter in Seminars in Neurology on FDA-approved and future monoclonal antibody treatments for multiple sclerosis. Tysabri (natalizumab) and Lemtrada (alemtuzumab) are currently available. Hopefully, both Ocrevus (ocrelizumab) and Zinbryta (daclizumab) will be available within the year. His chapter also covers remyelination antibodies being studied in clinical trials including opicinumab (Anti-LINGO-1) and rHIgM22.
In addition, Dr. Singer was extremely pleased to join the Board of Directors for the Multiple Sclerosis Association of America. As a global patient advocate, this position will allow him to further press for options for those living with multiple sclerosis.
From the MS Center for Innovations in Care, Danielle Scales, Dr. Singer, Vickie Kopf, and Delea Payne-Gates (left to right)
On April 17, 2016, Team MoBap had a great time participating in Walk MS with the Gateway Chapter of the National Multiple Sclerosis Society. Our team consisted of patients and staff committed to fundraising for critical research to repair MS damage and ultimately curing MS. Team MoBap was over 70 people strong and was the highest fundraising team. Dr. Barry Singer, the Walk MS chair, thanked the walkers and volunteers for their dedication and support!
Walk MS Speakers: Barry Singer, MD, Rebecca Fehlig, Chapter President of theGateway Chapter of National MS Society and Evelyn Sanguinetti, Illinois’ lieutenant governor living with MS (left to right)
Ocrelizumab becomes the FIRST therapy to show positive results in a Phase III clinical trial in PRIMARY PROGRESSIVE multiple sclerosis after numerous other failed trials with other medications.
In the ORATORIA study, ocrelizumab infusions in the vein reduced the risk of clinical disability progression compared to placebo in patients with primary progressive multiple sclerosis. The most common side effect was mild-to-moderate infusion-related reaction. The incidence of serious side effects (adverse events), including serious infections, was similar to placebo.
ORATORIO is a Phase III, randomized, double blind trial comparing ocrelizumab infusions to placebo in 732 primary progressive multiple sclerosis. The primary endpoint of the study was the time to onset of confirmed disability progression, sustained for at least 12 weeks. Ocrelizumab was given in the vein every 6 months as two 300 mg infusions two weeks apart.
Ocrelizumab targets specifically B-cells, a type of white blood cell lymphocyte. Another B-cell therapy, rituximab had failed in a previous primary progressive multiple sclerosis trial. Full abstract results coming next week at ECTRIMS in Barcelona.
Join us for The MS Center for Innovation in Care’s annual program focused on the latest updates in multiple sclerosis. The meeting takes place right after the largest global MS meeting called ECTRIMS in Barcelona, Spain in October. Over 8000 people focused on curing and treating MS will attend including Dr. Barry Singer and Dr. Mark Tullman. New therapies including some expected to be FDA-approved in 2016 will be discussed. The first MS treatment to work in primary progressive multiple sclerosis trials with be reviewed. Progress on myelin repair strategies will be highlighted including research at our center. Options for improving MS symptoms and quality of life will be addressed. A question and answer session will follow. Speakers include Barry Singer MD, Mark Tullman MD and Heather Popham, NP-C.
The FREE program is sponsored by Missouri Baptist Medical Center and will be held Thursday October 29, 2015 at the St. Louis Frontenac Hilton at 6:30 PM. Light refreshments will be served.