The Food and Drug Administration (FDA) has granted Priority Review designation for Ocrevus™ (ocrelizumab), an investigational treatment for relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS).
Approximately 95% of people with MS are initially diagnosed with either RMS or PPMS. If the FDA approves Ocrevus for both RMS and PPMS, the drug would be the first and only treatment indicated for both forms of MS.
Ocrevus is a humanized monoclonal antibody designed to selectively target CD20+ B cells, which are key contributors to the myelin and axonal damage that leads to disability in people with MS, according to the drug’s manufacturer Genentech, based in South San Francisco, CA.
Genentech’s application to the FDA was based on positive results from three phase III studies—OPERA I, OPERA II, and ORATORIO. Researchers presented results of these phase III trials on April 15, 2016 at the American Academy of Neurology’s (AAN) annual meeting, held in Vancouver, Canada. Here are some of their findings:
OPERA I and OPERA II
OPERA I and OPERA II are identical randomized, double-blind, multi-center studies that evaluated the efficacy and safety of ocrelizumab compared with conventional treatment of interferon beta 1-alpha in 1,656 people with RMS and secondary-progressive MS with relapses. At 96 weeks, patients treated with ocrelizumab showed a 40% reduced risk of confirmed disability progression (CDP) compared with patients given interferon beta 1-alpha.
Also, more patients treated with ocrelizumab had improved/stable disability (OPERA I: 92.3%; OPERA II: 87.5%) compared with patients treated with interferon beta 1-alpha (OPERA I: 86.1%; OPERA II: 80.4%), and significantly fewer patients had worsened disability with ocrelizumab vs interferon beta 1-alpha (OPERA I: 7.7% vs 13.9%; OPERA II: 12.5% vs 19.6%).
“These results show that CD20+ B-cell targeting with ocrelizumab has a robust effect in reducing disability progression in MS,” researchers concluded.
These trials also used serial brain MRI scanning to detect changes in central nervous system lesions. Compared with interferon beta 1-alpha, ocrelizumab reduced T1 gadolinium-enhancing lesions by 94% in OPERA I and by 95% in OPERA II, and decreased new/enlarging T2 hyperintense lesions by 77% in OPERA I and by 83% in OPERA II. Ocrelizumab reduced new T1 hypointense lesions by 57% in OPERA I and 64% in OPERA II, and slowed brain volume loss by 23.5% in OPERA I and by 23.8% OPERA II from baseline to week 96.
“Ocrelizumab significantly and consistently suppressed inflammatory and neurodegenerative markers of disease on MRI vs interferon beta 1-alpha in OPERA I and OPERA II over 96 weeks, with near-complete elimination of new T1 gadolinium-enhancing lesions following the first dose,” the investigators summarized.
ORATORIO is a randomized, double-blind, multi-center trial that evaluated ocrelizumab compared with placebo in 732 people with PPMS. Findings showed that patients treated with ocrelizumab reduced their relative risk of CDP by 24% at 12 weeks and by 25% at 24 weeks compared with patients on placebo. Patients in the ocrelizumab group also slowed their progression rate by 29% on a timed 25-foot walking test compared with those on placebo.
Also, serial brain MRI scanning showed that PPMS patients treated with ocrelizumab had reduced T2 lesion volume (-3.4%) compared with those on placebo (+7.4%), and a 17.5% reduced rate of brain volume loss (-0.9% with ocrelizumab vs -1.1% with placebo). Overall, adverse events and serious adverse events were similar in both groups.
“Ocrelizumab is the first investigational treatment to meet primary and key secondary efficacy outcomes in a phase III PPMS study,” the authors concluded.
The FDA’s Priority Review designation means that the agency has determined a drug to have the potential to provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared with standard applications. It also means the FDA aims to take action on an application within 6 months (compared to 10 months under standard review). For Ocrevus, the FDA set a targeted action date of December 28, 2016.