Roche announced that the European Commission (EC) has granted marketing authorisation for OCREVUS (ocrelizumab) for patients with active relapsing forms of multiple sclerosis defined by clinical or imaging features and for patients with early primary progressive multiple sclerosis in terms of disease duration and level of disability, and with imaging features characteristic of inflammatory activity. Multiple sclerosis (MS) affects approximately 700,000 people in Europe, of which around 96,000 have the highly disabling primary progressive form. Most people with MS have a relapsing form (RMS) or primary progressive MS (PPMS) at diagnosis.
“For people in Europe living with MS, today’s approval of OCREVUS by the European Commission signifies an important advance in the treatment of their disease,’’ said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “OCREVUS is the first medicine to be approved for primary progressive MS, a debilitating form in which irreversible disability accumulates rapidly, and it provides a highly efficacious treatment option for people with relapsing forms of MS. We are committed to working with member states to provide access as quickly as possible to people with RMS and PPMS who may benefit from OCREVUS.”
“It is great news that OCREVUS, which has the potential to be a significant game changer in how we think about and treat MS, has been approved in the European Union today,” said Gavin Giovannoni, Professor of Neurology at Barts and The London School of Medicine and Dentistry, Queen Mary University of London. “Until OCREVUS, people with primary progressive MS, who often have to rely on a cane or wheelchair, give up work or have carers look after them, have not had an approved treatment to slow the progression of their disease. People with relapsing forms of MS often have to make difficult trade-off choices between safety and higher efficacy. OCREVUS is given every six months without the need for onerous monitoring, which we hope will allow people to live their lives without thinking about their treatment every day or every week.”
The EU approval is based on data from three pivotal Phase III studies from the ORCHESTRA trial programme of 2,388 patients who met primary and nearly all key secondary endpoints. Data from two identical Phase III studies in relapsing forms of MS (OPERA I and OPERA II) showed OCREVUS demonstrated superior efficacy with approximately 80 percent of patients relapse free and significantly slower progression of the disease compared with high-dose interferon beta-1a (Rebif) over the two-year controlled treatment period. OCREVUS also significantly increased the chance of a patient having no evidence of disease activity (NEDA; brain lesions, relapses and worsening of disability) by 64 percent in OPERA I and 89 percent in OPERA II compared with high-dose interferon beta-1a (p<0.0001 and p<0.0001).
In a separate PPMS Phase III study (ORATORIO), OCREVUS was the first and only treatment to significantly slow disability progression and reduce signs of disease activity in the brain (MRI lesions) compared with placebo with a median follow-up of three years. Patients treated with OCREVUS were 24 percent less likely to have disability progression for three months and 25 percent less likely to have disability progression for six months (p=0.0321 and p=0.0365, respectively). OCREVUS also significantly slowed the progression of walking impairment by 29.4 percent, measured by the timed 25-foot walk, compared with placebo (p=0.0404).
The most common side effects associated with OCREVUS in all Phase III studies were infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity.
OCREVUS has been approved for use in countries across North America, South America, the Middle East, Eastern Europe, as well as in Australia and Switzerland. Over 30,000 people have been treated with OCREVUS to date.
About OCREVUS (ocrelizumab)
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 multiple sclerosis (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.
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.
About the OPERA I and OPERA II studies in relapsing forms of MS
OPERA I and OPERA II are Phase III, randomised, double-blind, double-dummy, global multi-centre studies evaluating 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. In these studies, relapsing MS (RMS) was defined as relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses. A similar proportion of patients in the OCREVUS group experienced serious adverse events and serious infections compared with patients in the high-dose interferon beta-1a group in the RMS studies.
About the ORATORIO study in primary progressive MS
ORATORIO is a Phase III, randomised, double-blind, global multi-centre study evaluating the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months; given as two 300 mg infusions two weeks apart) compared with placebo in 732 people with primary progressive MS (PPMS). The blinded treatment period of the ORATORIO study continued until all patients had received at least 120 weeks of either OCREVUS or placebo and a predefined number of confirmed disability progression (CDP) events was reached overall in the study. A similar proportion of patients in the OCREVUS group experienced adverse events and serious adverse events compared with patients in the placebo group in the PPMS study.
About OCREVUS pivotal Phase III trial results
A summary of the data from the OPERA I, OPERA II and ORATORIO studies that support this approval is below.
Key data in RMS patients treated with OCREVUS showed:
- A 46 percent and 47 percent relative reduction in the annualised relapse rate (ARR) compared with interferon beta-1a over the two-year period in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).
- A 40 percent relative risk reduction in confirmed disability progression (CDP) sustained for 12 weeks compared with interferon beta-1a in a pooled analysis of OPERA I and OPERA II, as measured by the Expanded Disability Status Scale (EDSS) (p=0.0006).
- A 94 percent and 95 percent relative reduction in the total number of T1 gadolinium-enhancing lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).
- A 77 percent and 83 percent relative reduction in the total number of new and/or enlarging T2 lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).
- A 64 percent and 89 percent relative increase in the proportion of patients with No Evidence of Disease Activity (NEDA) compared with interferon beta-1a in OPERA I and OPERA II, respectively (p<0.0001 and p<0.0001).
Key data in PPMS patients treated with OCREVUS showed:
- A 24 percent relative risk reduction in CDP sustained for at least 12 weeks compared with placebo, as measured by the EDSS (p=0.0321).
- A 25 percent relative risk reduction in CDP sustained for at least 24 weeks compared with placebo, as measured by the EDSS (p=0.0365).
- A 29.4 percent relative reduction in progression rate of walking impairment compared with placebo over 120 weeks measured by the timed 25-foot walk (p=0.0404).
- A 3.4 percent reduction in volume of brain hyperintense T2 lesions compared with a 7.4 percent increase in volume in placebo-treated patients over 120 weeks (p<0.0001).
The most common side effects associated with OCREVUS in all Phase III studies were infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity.
Filed Under: Drug Discovery
