New TNF inhibitor, Ozoralizumab

Abstract

  Ozoralizumab, a novel tumor necrosis factor（TNF）inhibitor, is an antibody drug that utilizes variable domains of heavy chain of heavy chain antibody（VHH）. It was approved in September 2022 in Japan for rheumatoid arthritis. Ozoralizumab is a trivalent bispecific antibody consisting of anti–human TNFα-VHHs and an anti–human serum albumin-VHH, with a molecular weight of 38 kDa, approximately one-fourth that of conventional IgG antibodies. Due to such low molecular weight and serum albumin binding ability, it is expected to be rapidly absorbed into the systemic circulation after subcutaneous administration and efficiently distributed to inflamed tissues. In fact, ozoralizumab was shown to enter the circulation more rapidly and distribute to inflamed joint tissue compared to IgG-type TNF inhibitors in a mouse model of collagen-induced arthritis. In a clinical study in combination with methotrexate, improvement in clinical symptoms was observed on day 3 of subcutaneous administration of ozoralizumab 30mg and the efficacy was maintained for 52 weeks. Based on these findings, ozoralizumab is considered to be a new type of TNF inhibitor that is expected to improve clinical symptoms rapidly.