Okrelizumab

Okrelizumab is a humanized anti-CD20 monoclonal antibody . It affects mature B-lymphocytes ^[1] and is thereby an immunosuppressant . It is jointly developed by Genentech and Biogen Idec, a subsidiary of Hoffmann-La Roche.

Okrelizumab achieved phase III clinical trials for rheumatoid arthritis ^[2] and systemic lupus erythematosus , ^[3] as well as phase II for multiple sclerosis (MS) ^[4] and lymphoma ^[5] .

In March 2010, Hoffmann-La Roche announced the early termination of clinical trials of okrelizumab for rheumatoid arthritis and systemic lupus erythematosus. This step followed reports of increased mortality in patients with these diseases who received okrelizumab from opportunistic infections. However, the development of okrelizumab as a treatment for multiple sclerosis continued, since there was no increased mortality from opportunistic infections among these patients ^[6] .

In October 2010, Hoffmann-La Roche announced the preliminary results of a 24-week phase II study in relapsing-remitting multiple sclerosis. Okrelizumab showed a statistically significant decrease in disease activity, as measured by the number of plaques in the brain on MRI and the relapse rate, compared with placebo. Both doses of okrelizumab (200 mg and 600 mg) were well tolerated.

In 2017, the US Food and Drug Administration (FDA) approved okrelizumab (under the Okrevus brand) as the first and, at the time of 2018, the only drug suitable for treating two forms of multiple sclerosis - primary progressive and recurrent.

In a separate study of phase III on PPRS (ORATORIO), OKREVUS was the first and only drug to significantly slow down the progression of disability and reduce the activity of the disease in MRI images compared with placebo with a median follow-up of 3 years. In the PPRS study, the relative number of patients with adverse events and serious adverse events in the okrelizumab and placebo groups was comparable. The most common adverse events were infusion reactions, as well as upper respiratory tract infections & nbsp; - mostly mild to moderate severity. The results of these phase III studies were published on January 19, 2017 in the New England Journal of Medicine (NEJM) ^[7] .

In the additional open stages of the OPERA I and OPERA II phase III trials, patients with recurrent multiple sclerosis who received continuous treatment with okrelizumab for five years had better results in assessing brain atrophy and confirmed progression of disability, compared with those patients who switched to okrelizumab after the first two years of treatment with interferon β-1a . Also, in patients who replaced interferon β-1 with okrelizumab after a controlled stage in the study, there was a rapid suppression of disease activity, determined by the average annual frequency of exacerbations and MRI indices ^[8] .