Ocrevus (ocrelizumab) for the Treatment of Multiple Sclerosis, United States of America
Developed by Genentech, Ocrevus (ocrelizumab) is indicated for the treatment of relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis.
The US Food and Drug Administration (FDA) granted breakthrough therapy designation for Ocrevus on 16 February 2016.
The biological license application (BLA) and marketing authorisation application (MAA) for Ocrevus were respectively accepted for review by the US FDA and European Medicines Agency (EMA) in June 2016.
Genentech has also submitted marketing applications for the drug in Switzerland and Australia. If approved, Ocrevus will be the first drug to be approved as a treatment for two forms of multiple sclerosis.
Multiple sclerosis types and symptoms
Multiple sclerosis (MS) is an autoimmune disease, which affects either the brain or spinal cord of the central nervous system. The condition causes serious damage to the myelin sheath of the nerves, which acts as a surrounding and protective layer.
MS is categorised into two types, relapsing MS and primary progressive MS. Relaspsing MS is associated with new episodes of symptoms or relapses, which repeat over a few days and can persist for months. Primary progressive MS is associated with gradually worsening symptoms over a number of years.
The disease normally includes symptoms such as fatigue, blurred vision, numbness in different parts of the body, muscle stiffness and spasms, problem in balancing and co-ordination of the body, loss of bladder control, and difficulty in thinking, learning, and planning.
Ocrevus' mechanism of action
Ocrevus is a humanised monoclonal antibody, which inhibits the growth of the CD20-positive B lymphoma cell lines, which play a major role in damaging nerve cells and the myelin sheath around the nerves.
Ocrelizumab selectively targets the CD20-positive B cells by binding to the surface proteins of the cells and protects the nerve cells from mediated damage caused by CD20-positive B lymphoma cell lines.
Clinical trials on Ocrevus
The BLA and MAA for Ocrevus were submitted based on the results obtained from the phase III clinical development programme named ORCHESTRA, which included three trials namely OPERA I, OPERA II and ORATORIO.
OPREA I and OPERA II were phase III, randomised, double-blind, multi-centre, identical studies conducted on 1,656 relapsing MS patients worldwide.
The trials were conducted to examine the safety and efficacy of ocrelizumab in comparison with interferon beta-1a. The subjects in the trial were randomised to receive either 600mg of Ocrelizumab administered intravenously every six months or 44mg of interferon beta-1a administered subcutaneously three times a week.
Both the trials met the primary and secondary end points of significantly reducing the annualised relapse rate (ARR) and delaying confirmed disability progression (CDP). Ocrelizumab reduced the ARR by 50% when compared to interferon beta-1a over a period of two years and delayed confirmed disability progression by 40% at both 12 weeks and 24 weeks when compared with interferon beta-1a.
In addition, Ocrelizumab significantly reduced inflammations, brain injury, number of T1 gadolinium-enhancing lesions and hyper intense T2 lesions associated with the disease.
ORATORIO was a phase III, randomised, double-blind, global multi-centre trial conducted on 732 patients with primary progressive multiple sclerosis. The subjects in the trial were randomised to receive either two infusions of 300mg of Ocrelizumab during the treatment cycle or placebo.
Ocrelizumab demonstrated a significant reduction in clinical disability progression (CDP) at 12 and 24 weeks, decreased the volume of T2 lesions and also reduced the rate of whole brain volume loss when compared to the placebo.
The most common adverse reactions observed during the trials were mild to moderate infusion-related reactions and infections.