Ozoralizumab: first Nanobody® therapeutic for rheumatoid arthritis

ABSTRACT

Introduction

Ozoralizumab (Nanozora), a novel TNF inhibitor, was first approved in Japan in September 2022 as a next-generation antibody for the treatment of rheumatoid arthritis (RA). Ozoralizumab potently inhibits TNF action through two human TNFα-binding domains, and a human serum albumin-binding domain that prolongs its plasma half-life enabling 4-week administration intervals. Its molecular weight is 38 kDa, which is one-fourth that of the conventional immunoglobulin G.

Areas covered

Structural characteristics of ozoralizumab, preclinical findings, clinical data, and its recommended positioning in current RA treatments have been summarized.

Expert opinion

Studies using mouse models have shown the rapid distribution of ozoralizumab in inflamed joint tissues, presumably because of its small molecular size and albumin-binding action. In clinical studies, remarkable improvements in clinical symptoms and patient-reported outcomes were observed 2 days after subcutaneous administration of 30 mg ozoralizumab with concurrent methotrexate therapy. Moreover, the efficacy and tolerability of the drug for up to 52 weeks, with or without methotrexate, were confirmed. Ozoralizumab is expected to be a highly practical option for patients with RA as a new type of TNF inhibitor with early symptom improvement despite subcutaneous administration.

KEYWORDS:

• Antirheumatic agent
• ozoralizumab
• rheumatoid arthritis
• tumor necrosis factor
• VHH

Article highlights

• Ozoralizumab is the first Nanobody® drug for rheumatoid arthritis.

• It has a long plasma half-life of 18 days because of its ability to bind albumin.

• Owing its small molecular size and ability to bind to albumin, it has a high distribution rate to inflammation sites, so its effect appears quickly.

• The improvement rate was equal to or greater than that of other TNF inhibitors and was maintained up to 52 weeks.

• Low immunogenicity caused by the lack of Fc region.

Declaration of Interest

Y Tanaka has received speaking fees and/or honoraria from Abbvie, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Pfizer, Taiho and Tisho and has received research grants from Chugai, Eisai, Taisho and Tanabe-Mitsubishi. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Taisho Pharmaceutical Co., Ltd.