Roche announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the investigational medicine ocrelizumab (OCREVUS) for the treatment of people with primary progressive multiple sclerosis (PPMS). There are currently no approved treatments for PPMS, a debilitating form of MS characterised by steadily worsening symptoms and typically without distinct relapses or periods of remission.
“Ocrelizumab is the first investigational medicine for MS to be granted Breakthrough Therapy designation by the FDA,” said Sandra Horning, M.D., Roche’s chief medical officer and head of global product development. “With no approved treatments for primary progressive MS, ocrelizumab has the potential to address an important unmet need. We are committed to working with the FDA to bring ocrelizumab to people with primary progressive MS as quickly as possible.”
Breakthrough Therapy designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. The designation is based on positive results from the pivotal phase III study (called ORATORIO), which showed treatment with ocrelizumab significantly reduced disability progression and other markers of disease activity compared with placebo. Top-line results were presented at the 31st congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in October 2015.
Roche plans to pursue marketing authorisation for both PPMS and relapsing multiple sclerosis (RMS), a more common form of the disease, and will submit data from three pivotal phase III studies to global regulatory authorities in the first half of 2016.
OCREVUS is the proprietary name submitted to global regulatory authorities for the investigational medicine ocrelizumab.
Ocrelizumab is an investigational, humanised monoclonal antibody designed to selectively target CD20-positive B cells. CD20-positive B cells are a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage, which can result in disability in people with MS. 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.
In addition to ORATORIO, the phase III clinical development programme for ocrelizumab includes OPERA I and OPERA II, which are randomised, double-blind, double-dummy, global multi-centre studies in people with relapsing forms of MS.
ORATORIO is a phase III, randomised, double-blind, global multi-centre study evaluating the efficacy and safety of ocrelizumab compared with placebo in 732 people with PPMS. The primary endpoint of the study was time to onset of confirmed disability progression (CDP) sustained for at least 12 weeks.
CDP measures a sustained protocol-defined increase in a patient’s Expanded Disability Status Scale (EDSS) score. The EDSS is based on a physical and neurological exam of eight systems throughout the body. The functional systems include vision, coordination, limb movement, strength, thinking abilities, bowel and bladder control, sensation and walking ability.
MS is a chronic disease that affects an estimated 2.3 million people around the world, for which there is currently no cure. MS 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. Damage to these nerves can cause a wide range of symptoms, including muscle weakness, fatigue and difficulty seeing, and may eventually lead to progressive disability.
PPMS is a debilitating form of MS characterised by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately one in 10 people with MS are diagnosed with the primary progressive form of the disease. There are no approved treatments for PPMS.