Pharmacological profiles and clinical efficacy of ozoralizumab (Nanozora® 30 ‍mg Syringes for S.C. Injection), the first Nanobody® compound in Japan

Abstract

Ozoralizumab, a novel TNF inhibitor, is the first NANOBODY® compound in Japan for rheumatoid arthritis. This compound consists of a humanized fusion protein with a trimeric structure having two anti-human TNFα NANOBODY® molecules and one anti-human serum albumin NANOBODY® molecule, and has the unique structure without an Fc portion. Ozoralizumab showed an inhibitory effect on TNFα-induced cell death, and its inhibitory concentration was lower than that of etanercept, adalimumab, and infliximab. Ozoralizumab also showed inhibitory effects on human TNFα-induced cellular infiltration in the murine air pouch model and reduced the arthritis scores in a murine rheumatoid arthritis model. In addition, ozoralizumab showed distinctive pharmacological characteristics different from the traditional IgG antibodies, which may be attributed to its unique structure, such as its ability to rapidly distribute to inflamed joint tissues in a murine rheumatoid arthritis model, and its immune complexes with TNFα do not induce inflammation in a murine subcutaneous inflammation model. In clinical trials, ozoralizumab demonstrated clinical efficacy in rheumatoid arthritis patients with inadequate response to methotrexate, which was observed from day 3 of treatment. Ozolalizumab also showed improvements in clinical symptoms in rheumatoid arthritis patients without methotrexate. The safety profile of the compound was not significantly different from that of current TNF inhibitors. Based on these results, ozoralizumab was approved in September 2022. Ozoralizumab shows early improvement of clinical symptoms in patients with rheumatoid arthritis, and its characteristic structure is expected to be new treatment options for patients who have an inadequate response to current bDMARDs.