FDA Delays Review of Multiple Sclerosis Drug Ocrevus

Manufacturing process requires further scrutiny

The FDA has extended the Prescription Drug User Fee Act (PDUFA) date for its review of the biologics license application for ocrelizumab (Ocrevus, Roche) to March 2017. The extension is the result of the submission of additional data by Roche regarding the commercial manufacturing process of ocrelizumab, which required additional time for FDA review. The extension is not related to the drug’s efficacy or safety.

Ocrelizumab is an investigational, humanized 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 axonal (nerve cell) damage, which can result in disability in people with multiple sclerosis (MS). Based on data from preclinical studies, ocrelizumab binds to CD20 cell-surface proteins expressed on certain B cells, but not on stem cells or plasma cells; therefore, important functions of the immune system may be preserved.

The phase 3 clinical development program for ocrelizumab (ORCHESTRA) includes three studies: OPERA I, OPERA II, and ORATORIO. OPERA I and OPERA II are identical randomized, double-blind, double-dummy, global studies that evaluated 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 subjects with relapsing forms of MS (i.e., relapsing-remitting MS and secondary-progressive MS with relapses). ORATORIO is a randomized, double-blind, global study that evaluated 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 subjects with primary progressive MS (PPMS).2

MS is a chronic disease that affects an estimated 2.3 million people worldwide. It occurs when the immune system abnormally attacks the insulation and support around nerve cells (the myelin sheath) in the brain, spinal cord, and optic nerves, causing inflammation and consequent damage. This damage can result in a wide range of symptoms, including muscle weakness, fatigue, and difficulty seeing, and may eventually lead to disability. Most people with MS experience their first symptoms between 20 and 40 years of age, making the disease the leading cause of nontraumatic disability in younger adults. There is no cure for MS.

Relapsing MS is the most common form of the disease. Disease activity and progression can occur even when people do not show signs or symptoms. PPMS is a debilitating form of the disease marked by steadily worsening symptoms without distinct relapses or periods of remission. Approximately 10% of people with MS are diagnosed with the primary progressive form of the disease.

Source: Roche; December 20, 2016.