“Controlling clinical and sub-clinical disease activity as early as possible is an important treatment goal for people living with MS”
OCREVUS increased disease control in patients with RMS and PPMS in separate post-hoc analyses. In these analyses, two composite endpoints measured disease control using a combination of clinical and MRI outcomes: No Evidence of Disease Activity (NEDA) in patients with RMS and No Evidence of Progression (NEP) in patients with PPMS. These composite endpoints are emerging as new treatment targets.
A NEDA analysis of pooled data from the Phase III OPERA I and OPERA II studies compared no evidence of disease activity during different time periods over two years of study. NEDA is achieved when a patient has no relapses, no confirmed disability progression, no gadolinium-enhancing MRI lesions and no new or enlarging MRI lesions. The data showed that OCREVUS significantly increased the proportion of RMS patients achieving NEDA by 75 percent compared with interferon beta-1a over 96 weeks (0-96 weeks, p<0.0001). Additionally, compared with interferon beta-1a, OCREVUS treatment significantly increased the relative proportion of patients achieving NEDA by 33 percent in weeks 0-24 and by 72 percent in weeks 24-96 (both p<0.0001). A majority of patients achieved NEDA in the first 24 weeks of OCREVUS treatment (60.8 percent) and this proportion increased during weeks 24-96 of the study (72.2 percent).
“Controlling clinical and sub-clinical disease activity as early as possible is an important treatment goal for people living with MS,” said Professor Gavin Giovannoni, Scientific Steering Committee Member of the OPERA I and II studies and Chair of Neurology at Barts and The London School of Medicine and Dentistry. “These new data suggest that ocrelizumab consistently impacts disease progression and has the potential to change how we approach treating both relapsing and primary progressive MS.”
New post-hoc analyses of the ORATORIO study in PPMS patients measured NEP, which includes three measures of physical disability (confirmed disability progression, walking speed and upper extremity function) and reflects no evidence of worsening of a person’s physical disability. Patients who achieved NEP had no evidence of confirmed disability progression sustained for at least 12 weeks and less than 20 percent worsening of performance on the timed 25-foot walk and 9-hole peg test. OCREVUS treatment significantly increased the proportion of PPMS patients with NEP by 47 percent at week 120 compared with placebo (p=0.0006).
“With no approved treatment options, primary progressive MS remains a challenge for physicians and people with MS,” said Xavier Montalban, M.D., Ph.D., Professor of Neurology and Neuroimmunology at Vall d’Hebron University Hospital, Research Institute and Cemcat, Barcelona, Spain. “OCREVUS significantly impacted three key disability measurements, which further highlight its clinical significance in people with primary progressive MS.”
In addition, new patient-reported outcomes data from the ORATORIO study highlighting the unmet need of people with PPMS, including the effect OCREVUS had on fatigue measures, will be presented.
Leading investigators will present the following oral and poster presentations:
Abstract Number (type),
|An exploratory analysis of 12- and 24-week composite confirmed disability progression in patients with primary progressive multiple sclerosis in the ORATORIO trial||P746 (poster), Thursday, September 15, 3:45 – 5:00 p.m. BST|
|Infusion-related reactions with ocrelizumab in relapsing multiple sclerosis and primary progressive multiple sclerosis||P720 (poster), Thursday, September 15, 3:45 – 5:00 p.m. BST|
|Evaluation of no evidence of progression using composite disability outcome measures, in patients with primary progressive multiple sclerosis in the ORATORIO trial||167 (oral), Friday, September 16, 9:51 – 10:03 a.m. BST|
|Effect of ocrelizumab on magnetic resonance imaging markers of neurodegeneration in patients with relapsing multiple sclerosis: analysis of the Phase III, double-blind, double-dummy, interferon beta-1a-controlled OPERA I and OPERA II studies||P1011 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST|
|Patient-reported outcomes in the Phase III double-blind, placebo-controlled ORATORIO study of ocrelizumab in primary progressive multiple sclerosis||P1279 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST|
|Infections and serious infections with ocrelizumab in relapsing multiple sclerosis and primary progressive multiple sclerosis||P1248 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST|
|Design of two phase III open-label trials evaluating ocrelizumab in patients with relapsing-remitting multiple sclerosis and suboptimal response to disease-modifying treatment||P1180 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST|
|Baseline assessment of fatigue and health-related quality of life in patients with primary progressive multiple sclerosis in the ORATORIO study||P1278 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST|
|Exploration and verification of a patient-powered research network to provide patient insights in multiple sclerosis||P889 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST|
|NEDA epoch analysis of patients with relapsing multiple sclerosis treated with ocrelizumab: Results from OPERA I and OPERA II, Phase III studies||P1593 (poster), Friday, September 16, 3:30 – 5:00 p.m. BST|
|Real-world treatment observation in multiple sclerosis: development of an online platform to measure patients’ treatment awareness and experiences, access barriers and decision-making||ePoster will be displayed on terminals during the congress|
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As previously announced, the U.S. Food and Drug Administration (FDA) accepted for review the company’s Biologics License Application (BLA) for OCREVUS for the treatment of RMS and PPMS, and granted the application Priority Review Designation with a targeted action date of December 28, 2016.
OCREVUS™ is the proprietary name submitted to the FDA for the investigational medicine ocrelizumab.
About OCREVUS™ (ocrelizumab)
OCREVUS is an investigational, humanized monoclonal antibody designed to selectively target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can lead to disability in people with MS. Based on preclinical studies, OCREVUS binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved.
The Phase III clinical development program for OCREVUS (ORCHESTRA) includes three studies: OPERA I, OPERA II and ORATORIO. OPERA I and OPERA II are identical Phase III, randomized, double-blind, double-dummy, global multi-center studies that evaluated the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months) compared with interferon beta-1a (44 mcg administered by subcutaneous injection three times per week) in 1,656 people with relapsing forms of MS (i.e., relapsing-remitting MS and secondary-progressive MS with relapses). ORATORIO is a Phase III, randomized, double-blind, global multi-center study that evaluated the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months) compared with placebo in 732 people with primary progressive MS (PPMS).
The most common adverse events associated with OCREVUS were infusion-related reactions and infections, which were mostly mild to moderate in severity.