Date: 01-May-2020

Roches Phase III OPERA I & OPERA II Studies Show That Ocrevus Treatment Reduces Risk Of Disease And Disability Progression In RMS And PPMS

Roche announced new analyses of phase III OPERA I and OPERA II studies, as well as the open-label extensions, showing that Ocrevus (ocrelizumab) treatment reduced the risk of disease and disability progression in RMS and PPMS. These new analyses add additional evidence to the benefit-risk profile of Ocrevus, including the impact of MS on people’s daily lives. The data were selected for the 72nd American Academy of Neurology (AAN) Annual Meeting and will be made available online via virtual presentation in the coming weeks.

“For people with MS, maintaining mobility for as long as possible is very important. We are encouraged by these new longer-term analyses showing that earlier initiation of Ocrevus treatment may reduce the risk of needing a walking aid by nearly 50 percent over six years,” said Levi Garraway, M.D., Ph.D., Roche's chief medical officer and Head of Global Product Development. “Slowing MS progression earlier in the disease course – not just treating relapses – may bring additional clinically meaningful outcomes to people living with this disease.”

Earlier treatment with Ocrevus may delay the risk of needing a walking aid compared to those who switched from interferon beta-1a two years later in a new post-hoc analysis from the open-label extension of the phase III OPERA studies in RMS. The risk was measured by the length of time until a person reached a score on the Expanded Disability Status Scale of 6 or greater (EDSS=6) that was sustained for at least 48 weeks. People treated with Ocrevus had a 49% reduction in the risk of needing a walking aid compared to those that received interferon beta-1a over 6 years of study (4.3% vs. 7.2%; p=0.0042). Safety profiles in the double-blind period and open-label extension were generally consistent.

Ocrevus progressively slowed thalamic atrophy (as measured by change in thalamic volume) in patients with RMS or PPMS. Results from the double-blind periods of the phase III OPERA I, OPERA II and ORATORIO studies showed significantly less thalamic atrophy compared with interferon beta-1a and placebo, respectively (both p<0.001). The thalamus is a deep grey matter structure within the brain that acts as a relay and integrative centre, playing a key role in alertness, motor control and cognition, as well as sensory processing. It is affected by MS-related damage and its atrophy could be a useful marker of therapeutic efficacy.

With rapidly growing real-world experience and more than 150,000 patients treated globally, Ocrevus has twice-yearly (six-monthly) dosing and is the first and only therapy approved for RMS (including relapsing-remitting MS (RRMS) and active, or relapsing, secondary progressive MS (SPMS), in addition to clinically isolated syndrome in the US) and PPMS. Ocrevus is approved in 90 countries across North America, South America, the Middle East, Eastern Europe, as well as in Australia, Switzerland and the European Union.

Multiple sclerosis (MS) is a chronic disease that affects nearly 1 million people in the US and more than 2.3 million people worldwide. MS occurs when the immune system abnormally attacks the insulation and support around nerve cells (myelin sheath) in the central nervous system (brain, spinal cord and optic nerves), causing inflammation and consequent damage. This damage can cause a wide range of symptoms, including muscle weakness, fatigue and difficulty seeing, and may eventually lead to disability. Most people with MS experience their first symptom between 20 and 40 years of age, making the disease the leading cause of non-traumatic disability in younger adults.

People with all forms of MS experience disease progression – permanent loss of nerve cells in the central nervous system and gradual worsening of disability – at the beginning of their disease even if their clinical symptoms aren’t apparent or don’t appear to be getting worse. Delays in diagnosis and treatment can negatively impact people with MS, both in terms of their physical, mental and financial health. An important goal of treating MS is to slow the progression of disability as early as possible.

Relapsing-remitting MS (RRMS) is the most common form of the disease and is characterised by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. Approximately 85% of people with MS are initially diagnosed with RRMS. The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive MS (SPMS), in which they experience steadily worsening disability over time. Relapsing forms of MS (RMS) include people with RRMS and people with SPMS who continue to experience relapses. Primary progressive MS (PPMS) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately 15% of people with MS are diagnosed with the primary progressive form of the disease. Until the FDA approval of Ocrevus, there had been no FDA approved treatments for PPMS.

Ocrevus is the first and only therapy approved for both RMS (including clinically isolated syndrome, RRMS and active, or relapsing, SPMS in the US) and PPMS, with dosing every six months. Ocrevus is a humanised monoclonal antibody designed to 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, suggesting that important functions of the immune system may be preserved. Ocrevus is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.