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 ( PPMS ) in terms of disease duration and level of disability, and with imaging features characteristic of inflammatory activity.
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 multiple sclerosis ( OPERA I and OPERA II ) showed Ocrelizumab demonstrated superior efficacy with approximately 80% 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.
Ocrelizumab has also significantly increased the chance of a patient having no evidence of disease activity ( NEDA; brain lesions, relapses and worsening of disability ) by 64% in OPERA I and 89% in OPERA II compared with high-dose Interferon beta-1a ( p less than 0.0001 and p less than 0.0001 ).
In a separate PPMS phase III study ( ORATORIO ), Ocrelizumab 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 Ocrelizumab were 24% less likely to have disability progression for three months and 25% less likely to have disability progression for six months ( p=0.0321 and p=0.0365, respectively ).
Ocrelizumab has also significantly slowed the progression of walking impairment by 29.4%, measured by the timed 25-foot walk, compared with placebo ( p=0.0404 ).
The most common side effects associated with Ocrelizumab in all phase III studies were infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity.
Ocrelizumab 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.
Based on preclinical studies, Ocrelizumab 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. ( Xagena )
Source: Roche, 2018