The U.S. Food and Drug Administration ( FDA ) has approved Ocrevus ( Ocrelizumab ) as the first and only medicine for both relapsing and primary progressive forms of multiple sclerosis.
The majority of people with multiple sclerosis have a relapsing form or primary progressive multiple sclerosis at diagnosis.
In two identical RMS Phase III studies ( OPERA I and OPERA II ), Ocrelizumab has demonstrated superior efficacy on the three major markers of disease activity by reducing relapses per year by nearly half, slowing the worsening of disability and significantly reducing MRI lesions compared with Rebif ( high-dose Interferon beta-1a ) over the two-year controlled treatment period.
A similar proportion of people in the Ocrelizumab group experienced a low rate of serious adverse events and serious infections compared with people in the high-dose Interferon beta-1a group in the relapsing multiple sclerosis studies.
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.
A similar proportion of people in the Ocrelizumab group experienced adverse events and a low rate of serious adverse events compared with people in the placebo group in the PPMS study.
The most common side effects associated with Ocrelizumab in all phase III studies included infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity.
Results from these three phase III studies were recently published in the New England Journal of Medicine ( NEJM ).
OPERA I and OPERA II are randomized, double-blind, double-dummy, global multi-center studies evaluating the efficacy and safety of Ocrelizumab ( 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 multiple sclerosis.
In these studies, relapsing multiple sclerosis was defined as relapsing-remitting multiple sclerosis ( RRMS ) and secondary progressive multiple sclerosis ( SPMS ) with relapses.
ORATORIO is a phase III, randomized, double-blind, global multi-center study evaluating the efficacy and safety of Ocrelizumab ( 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 PPMS. The blinded treatment period of the ORATORIO study continued until all patients had received at least 120 weeks of either Ocrelizumab or placebo and a predefined number of confirmed disability progression ( CDP ) events was reached overall in the study.
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.
Potential serious side effects may include infusion reactions, infections and malignancies where only routine screening is required based on age and medical history.
Multiple sclerosis is a chronic disease that affects an estimated 400,000 people in the U.S., for which there is currently no cure. Multiple sclerosis occurs when the immune system abnormally attacks the insulation and support around nerve cells ( myelin sheath ) in the 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 multiple sclerosis experience their first symptom between 20 and 40 years of age, making the disease the leading cause of non-traumatic disability in younger adults.
Relapsing-remitting multiple sclerosis ( RRMS ) is the most common form of the disease and is characterized by episodes of new or worsening signs or symptoms ( relapses ) followed by periods of recovery. Approximately 85% of people with multiple sclerosis are initially diagnosed with RRMS.
The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive multiple sclerosis ( SPMS ), in which they experience steadily worsening disability over time.
Relapsing forms of multiple sclerosis ( RMS ) include people with RRMS and people with SPMS who continue to experience relapses.
Primary progressive multiple sclerosis ( 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 multiple sclerosis are diagnosed with the primary progressive form of the disease.
People with all forms of multiple sclerosis experience disease activity, inflammation in the nervous system and permanent loss of nerve cells in the brain, even when their clinical symptoms aren’t apparent or don’t appear to be getting worse.
An important goal of treating multiple sclerosis is to reduce disease activity as soon as possible to slow how quickly a person’s disability progresses.
Despite available disease-modifying treatments, some people with RMS continue to experience disease activity and disability progression.
Ocrelizumab is a 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 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 first dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.
Ocrevus is a prescription medicine used to treat adults with relapsing or primary progressive forms of multiple sclerosis.
It is not known if Ocrevus is safe or effective in children. ( Xagena )
Source: Genentech, 2017