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.
READ ABOUT OTHER TREATMENT OPTIONS
Here’s a few highlights of the meeting:
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)
Curing MS and repairing disease damage requires innovative, groundbreaking research. Funding for research is critical. That’s why we need YOU!
Support the National Multiple Sclerosis Society by joining or donating to Team MoBap. STAFF, PATIENTS, FRIENDS and FAMILY ARE INVITED on our team.
Walk MS is Sunday April 17 2016 at Forest Park Upper Muny Lot. Registration 1 PM, Start 2 PM.
REGISTER OR DONATE HERE!
GATEWAYWALKMS.ORG | 1-800-344-4867
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.
REGISTER at 314-996-LIFE. Love to see you there!
Myelin repair strategies are being pursued to repair old myelin damage in multiple sclerosis patients and to improve remyelination after an acute exacerbation. Encouraging to see these potential remyelinating treatments enter clinical trial phases! Clearly, a huge need is treatment to repair myelin and hopefully improve disability for those living with MS.
Through screening over 125,000 Mayo Clinic patient blood samples, a human monoclonal antibody was found that promoted remyelination in animal models of MS. A phase 1, multi-center, double-blind randomized study was conducted using a recombinant version of this antibody, rHIgM22. A single dose of rHIgM22 was given in the vein to 55 MS patients and 17 patients received placebo. Headache and contact dermatitis were reported, but no MRI or laboratory safety issues. The MS Center for Innovations in Care at Missouri Baptist Medical Center was one of the sites for this phase 1 clinical trial. A second phase 1 trial is planned to assess the safety and tolerability of rHIgM22 immediately following a relapse.
LINGO-1 is a glycoprotein on neurons and oligodendrocytes (myelin-making cells) in the central nervous system that blocks myelination. In the RENEW Trial, 82 patients with acute optic neuritis affecting one eye were randomized anti-LINGO-1 antibody BIIB033 or placebo infusions every 4 weeks for 6 total doses. Anti-LINGO-1 treatment had better outcomes than placebo on the full-field visual evoked potentials (P=0.05). An ongoing phase 2 trial of anti-LINGO-1 treatment is being examined in patients with relapsing multiple sclerosis while staying on Avonex.
Semaphorin 4D signaling blocks remyelination. Anti-semaphorin 4D (Anti-SEMA 4D) monoclonal antibody protects against loss of myelin and enhancing myelin repair in animal models of MS. A phase 1 study of VX15/2503, an anti-SEMA 4D antibody, showed that the antibody treatment was well-tolerated without serious safety issues.
Ocrelizumab is an anti-CD20 antibody therapy given as an infusion every 6 months. Ocrelizumab temporarily knocks out B cells, an important immune cell involved in causing damage in multiple sclerosis. Two Phase 3 clinical trials (OPERA I and II) were conducted to evaluate ocrelizumab in relapsing multiple sclerosis. In both trials, patients were randomized to Rebif or ocrelizumab 600 mg intravenously every 24 weeks. Only the first dose of ocrelizumab was divided into 300 mg on Day 1 and Day 15. OPERA I and II randomized 821 and 835 patients, respectively.
Treatment with ocrelizumab significantly reduced the number of relapses per year (annualized relapse rate), the risk of disability progression and reduced the number of brain lesions compared to Rebif treatment. Results were just announced in a press release. Exact difference will be presented at a future scientific meeting.
The most common side effects of ocrelizumab were mild-to-moderate infusion-related reactions. The incidence of serious infections on ocrelizumab was similar to Rebif.
The MS Center for Innovations in Care was a site for the OPERA clinical program.
Reporting live from Washington, DC.
Multiple sclerosis in children is becoming increasingly recognized. The focus has been on earlier diagnosis. Many children can have only one attack such as optic neuritis or ADEM (acute disseminated encephalomyelitis) in which multiple active areas of inflammation occurred in the brain and spinal cord. Data was presented on MRI findings and environmental factors (low vitamin D levels and Epstein-Barr virus exposure) that predict risk of developing multiple sclerosis.
Daclizumab data was presented. In the DECIDE Trial, 1841 patients were randomized to daclizumab or Avonex. Daclizumab reduced new relapses by 54%, reduced contrast-enhancing lesions by 65% and reduced confirmed progression of disability at 6 months by 27%. Infections and skin reactions (37%) were higher on daclizumab.
SMART study examined 2455 multiple sclerosis patients treated with Gilenya. Only one patient had symptoms from low pulse. LONGTERMS study of patients on Gilenya for an average of 4 years results showed no increase risk of infection in patients with low lymphocyte (type of white blood cell) counts. Low lymphocytes was defined as absolute lymphocyte count <0.4 for 60% or more of labs checked on treatment.
Lemtrada-treated patients with no previous treatment with multiple sclerosis treatment generally had good 4 year response. Forty-two percent of patients actually had improvement in disability and 31 % of patients remained stable despite very active disease entering the trial.
JC virus index has been useful in examining PML risks. Of a group of 68 patients with PML without previous immunosuppressive medication exposure, only 2 patients (2.9%) had a JC virus index less than or equal to 0.9. Since PML can be fatal, Tysabri risks must be weighed against treatment benefits.