The U.S. Food and Drug Administration recently extended until the end of March its review of the Biologics License Application (BLA) for Ocrevus (ocrelizumab). The application was submitted by Roche, requesting FDA approval for Ocrevus as a treatment for patients with relapsing-remitting multiple sclerosis (RRMS) and — for a first time — for those with primary progressive multiple sclerosis (PPMS) as well.
Roche had submitted additional data to the agency on the manufacturing process of Ocrevus, which resulted in the FDA moving its expected decision date to March 28, 2017. The additional information provided does not concern the efficacy or safety of Ocrevus, the company said in a news release.
“We strongly believe in the potential of OCREVUS as a new therapeutic option for both people with relapsing forms of multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS),” Sandra Horning, MD, chief medical officer at Roche, said in the release. “We are working closely with the FDA during their review and committed to bringing this innovative medicine to the over 400,000 people with MS in the US living with this disabling disease as quickly as possible.”
Ocrevus is a humanized antibody that targetd CD20-positive B-cells, a type of immune system cell that is believed to contribute to myelin degeneration and neuronal damage, the hallmarks of MS.
The BLA was based on the positive results obtained in three Phase 3 clinical trials assessing Ocrevus as a treatment for both RRMS and PPMS.
The studies OPERA I and OPERA II (NCT01412333) evaluated the efficacy of intravenous administration of Ocrevus 600 mg every six months, compared to Rebif (interferon beta-1a) as a control therapy, in more than 1,600 RRMS patients. Pooled trial data demonstrated that, with Ocrevus treatment, a significant number of relapsing MS patients (75 percent) achieved No Evidence of Disease Activity (NEDA) status — meaning no relapses, no confirmed disability progression, no gadolinium-enhancing MRI lesions, and no new or enlarging MRI lesions — over 96 weeks compared to those in the control group.
The ORATORIO study (NCT01194570) evaluated the efficacy and safety of Ocrevus (intravenously injection of 600 mg every six months) in 732 patients with PPMS by measuring three parameters of physical disability that define No Evidence of Disease Progression (NEP) in these patients — confirmed disease progression, walking speed, and upper extremity function. Results indicated that, some two years after treatment with Ocrevus, a significant number of PPMS patients (47 percent) achieved NEP compared to a control arm given placebo.
“These results redefine our understanding of MS by highlighting the central role of the B cell,” said Stephen Hauser, MD, chair of the Scientific Steering Committee of the OPERA studies and chair of the Department of Neurology at the University of California, San Francisco, School of Medicine. “The findings may also encourage the MS community to look more closely at earlier treatment of the disease. Currently, many doctors reserve what are considered highly effective MS medicines until a patient’s disease becomes more advanced. Patients and their doctors need new treatment options that offer the potential for greater efficacy than a standard-of-care interferon with a similar safety profile.”
These results also led the FDA to designate Ocrevus a Breakthrough Therapy in February.
“This is an important moment for the MS community,” said Xavier Montalban, MD, PhD, chair of the Scientific Steering Committee of the ORATORIO study and a professor of Neurology and Neuroimmunology at Vall d’Hebron University Hospital and Research Institute, Barcelona, Spain. “For decades, trial after trial has failed to show the benefit of any medicine for people with primary progressive MS. Now, for the first time, we have a positive Phase III study result for people with this debilitating form of the disease.”