Nanozora (ozoralizumab) / EddingPharm, Sanofi, Taisho - LARVOL DELTA

New anti-TNF biologics in RA: What is new and what is old? (PubMed, Semin Arthritis Rheum) - "This review summarizes the recent advancement of fragmented immunoglobulin molecules targeting on Tumot Necrosis Factor (TNF) alpha and highlighted the nanobody, which is the first approved product for the patients with rheumatoid arthritis (RA), ozoralizumab (OZR)...It has been approved in Japan in 2022 and marked as the fixth products of TNF inhibitors for RA in Japan. The similarities and differences among these products are discussed in this review."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Efficacy of ozoralizumab based on baseline RF titres in patients with RA: A post hoc analysis of the OHZORA trial (EULAR 2025) - No abstract available

Clinical • Retrospective data

Ozoralizumab shows effectiveness regardless of baseline RF and ACPA titres in patients with RA: A post hoc analysis of the OHZORA trial. (PubMed, Rheumatology (Oxford)) - "OZR is an effective anti-TNF treatment for RA, regardless of RF and ACPA titres, and exhibits promise as a novel therapeutic option."

Journal • Retrospective data • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Rapid improvement of rheumatoid arthritis symptoms with ozoralizumab: a case of progress monitored by musculoskeletal ultrasonography. (PubMed, Scand J Rheumatol) - No abstract available

Journal • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Rheumatoid Arthritis • Rheumatology

Research trends in the use of nanobodies for cancer therapy. (PubMed, J Control Release) - "In recent years, several nanobody-based drugs, including Caplacizumab, KN-035, and Ozoralizumab, have been approved for clinical use. Future trends were also predicted. This study provides a unique, comprehensive, and objective perspective on the use of nanobodies in tumor research, laying a foundation for future research directions and offering valuable insights for researchers in the field."

Journal • Review • Infectious Disease • Oncology • Solid Tumor • Targeted Protein Degradation

Effect of Ozoralizumab Administration with or without Methotrexate in Patients with Rheumatoid Arthritis: A Post-Hoc Analysis. (PubMed, Rheumatol Ther) - "OZR administration without MTX was associated with an improvement in the signs and symptoms of RA compared to placebo administration (continuation of MTX monotherapy). OZR and MTX administration showed better efficacy than OZR administration alone."

Journal • Retrospective data • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Correction: Long-term safety and efficacy of anti-TNF multivalent VHH antibodies ozoralizumab in patients with rheumatoid arthritis. (PubMed, RMD Open) - No abstract available

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Acute Heart Failure with Reduced Ejection Fraction Following Ozoralizumab in A Patient with Rheumatoid Arthritis: A Case Report. (PubMed, Mod Rheumatol Case Rep) - "Her condition improved after OZR discontinuation, suggesting that OZR may have precipitated the HFrEF despite tolerance with previous TNF inhibitors. Further studies are warranted to elucidate the mechanism and incidence of OZR-associated HF."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Long-term safety and efficacy of anti-TNF multivalent VHH antibodies ozoralizumab in patients with rheumatoid arthritis. (PubMed, RMD Open) - P3 | "This integrated analysis revealed no new safety concerns, and the efficacy was maintained in patients with RA under long-term ozoralizumab administration."

Journal • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Single domain antibody: Development and application in biotechnology and biopharma. (PubMed, Immunol Rev) - "The introduction of commercial nanobody drugs such as Cablivi, Nanozora, Envafolimab, and Carvykti has boosted confidence among in their potential. This review explores the evolutionary history of HCAbs, their ontogeny, and applications in biotechnology and pharmaceuticals, focusing on approved and ongoing medical research pipelines."

Journal • Review

Development of a novel bacterial production system for recombinant bioactive proteins completely free from endotoxin contamination. (PubMed, PNAS Nexus) - "Moreover, we applied our system to produce ozoralizumab, a multispecific VHH that binds to human TNF-α and albumin and are marketed as a rheumatoid arthritis drug. We successfully purified a functional antibody from endotoxin contamination. This system establishes a new, completely endotoxin-free platform for the expression of recombinant proteins, which distinguishes it from other bacterial expression systems, and holds promise for future applications."

Journal • Immunology • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • TNFA

Structural design of the anti-TNFα therapeutic NANOBODY® compound, ozoralizumab, to support its potent and sustained clinical efficacy. (PubMed, Biochem Biophys Res Commun) - No abstract available

Journal

Systematic review and meta-analysis for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis. (PubMed, Mod Rheumatol) - "This systematic review provides latest evidence for the 2024 update of the JCR CPG for RA management."

Clinical guideline • Journal • Retrospective data • Review • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Next-Generation Anti-TNFα Agents: The Example of Ozoralizumab. (PubMed, BioDrugs) - "In clinical trials, ozoralizumab yielded an early improvement in clinical symptoms, a sustained efficacy for up to 52 weeks, and an acceptable tolerability in patients with rheumatoid arthritis. This review focuses on the results of pre-clinical and clinical trials for ozoralizumab and outlines the progress in next-generation antibody development."

Journal • Review • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

A pivotal decade for bispecific antibodies? (PubMed, MAbs) - "Nevertheless, only three bsAbs (catumaxomab, blinatumomab, emicizumab) were approved through the end of 2020. However, since then, 11 bsAbs received regulatory agency approvals, of which nine (amivantamab, tebentafusp, mosunetuzumab, cadonilimab, teclistamab, glofitamab, epcoritamab, talquetamab, elranatamab) were approved for the treatment of cancer and two (faricimab, ozoralizumab) in non-oncology indications. Notably, of the 13 currently approved bsAbs, two, emicizumab and faricimab, have achieved blockbuster status, showing the promise of this novel class of therapeutics. In the 2020s, the approval of additional bsAbs can be expected in hematological malignancies, solid tumors and non-oncology indications, establishing bsAbs as essential part of the therapeutic armamentarium."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor

Efficacy of ozoralizumab based on baseline rheumatoid factor titers in patients with rheumatoid arthritis and an inadequate response to methotrexate: Post hoc analysis of a Phase II/III study (OHZORA trial) (JCR 2024) - No abstract available

Clinical • P2/3 data • Retrospective data • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Pharmacological profiles and clinical efficacy of ozoralizumab (Nanozora 30 ‍mg Syringes for S.C. Injection), the first Nanobody compound in Japan (PubMed, Nihon Yakurigaku Zasshi) - "Ozoralizumab showed an inhibitory effect on TNFα-induced cell death, and its inhibitory concentration was lower than that of etanercept, adalimumab, and infliximab...In clinical trials, ozoralizumab demonstrated clinical efficacy in rheumatoid arthritis patients with inadequate response to methotrexate, which was observed from day 3 of treatment...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."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Population pharmacokinetics of ozoralizumab in patients with rheumatoid arthritis. (PubMed, J Clin Pharmacol) - "Body weight, sex, anti-drug antibody status, estimated glomerular filtration rate, and concomitant methotrexate use were identified as covariates for CL/F, while body weight and sex were covariates for V /F in the final model. When administered at 30 mg every 4 weeks, the predicted steady-state plasma trough concentration in a patient weighing 83.2 kg exceeded the trough concentration required to maintain efficacy of ozoralizumab, and the estimated exposure in a patient weighing 42.5 kg did not exceed the mean exposure at 80 mg, a well-tolerated dose, throughout 52 weeks. We developed a population PK model that adequately described the ozoralizumab PK in Japanese patients with RA, and none of the evaluated covariates showed clinically relevant effects on the PK of ozoralizumab."

Journal • PK/PD data • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology • TNFA

Effect of extended dosing interval of anti-TNF-alpha NANOBODY® compound ozoralizumab in patients with low disease activity rheumatoid arthritis. (PubMed, Mod Rheumatol) - "In patients with RA and maintained DAS28-ESR <3.2 with ozoralizumab, efficacy was sustained and well tolerated after the dosing interval was extended from Q4W to Q8W."

Journal • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Isolation and Characterization of Single-Domain Antibodies from Immune Phage Display Libraries. (PubMed, Methods Mol Biol) - "The first approved VH, a bivalent humanized VH (caplacizumab), was approved for treating rare blood clotting disorders in 2018 by the EMA and the FDA in 2019. This was followed by the approval of an anti-BCMA VH-based CAR-T cell product in 2022 (ciltacabtagene autoleucel; CARVYKTI™) and more recently a trivalent antitumor necrosis factor alpha-based VH drug (ozoralizumab; Nanozora) in Japan for the treatment of rheumatoid arthritis...This includes protocols for expression, biotinylation, purification, and characterization of the isolated VHs. To demonstrate the feasibility of the entire strategy, we present examples of VHs previously isolated and characterized in our laboratory."

IO biomarker • Journal • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology • Thrombosis • TNFA

Ozoralizumab: first Nanobody® therapeutic for rheumatoid arthritis. (PubMed, Expert Opin Biol Ther) - "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."

Journal • Review • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Inducer-free recombinant protein production in Trichoderma reesei: secretory production of endogenous enzymes and heterologous nanobodies using glucose as the sole carbon source. (PubMed, Microb Cell Fact) - "In general, whereas the replacement of major cellulase genes leads to extreme decrease in the degradation capacity of cellulose, our inducer-free system enabled it and achieved high secretory production of POI with increased occupancy in glucose medium. This system would be a novel platform for heterologous recombinant protein production in T. reesei."

Journal

Structural, nonclinical, and clinical features of ozoralizumab: A novel tumour necrosis factor inhibitor. (PubMed, Mod Rheumatol) - "This review summarizes OZR's unique structural characteristics and nonclinical and clinical data. The clinical data outline the pharmacokinetics, efficacy, relationship between efficacy and pharmacokinetics, and safety of OZR, focusing on a Phase II/III confirmatory study (OHZORA trial)."

Journal • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

An Extension Study of TS-152 in Subjects With Rheumatoid Arthritis (clinicaltrials.gov) - P3 | N=401 | Completed | Sponsor: Taisho Pharmaceutical Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Unique structure of ozoralizumab, a trivalent anti-TNFα NANOBODY compound, offers the potential advantage of mitigating the risk of immune complex-induced inflammation. (PubMed, Front Immunol) - "In this study, in order to elucidate the mechanism underlying the reduced incidence of ISRs associated with ozoralizumab administration, we investigated the stoichiometry of two TNFα inhibitors (ozoralizumab and adalimumab, an anti-TNFα IgG) ICs and the induction by these drugs of Fcγ receptor (FcγR)-mediated immune responses on neutrophils. We also developed a model of anti-TNFα antibody-TNFα IC-induced subcutaneous inflammation and found that ozoralizumab-TNFα ICs do not induce any significant inflammation at injection sites. The results of our studies suggest that ozoralizumab is a promising candidate for the treatment of RA that entails a lower risk of the IC-mediated immune cell activation that leads to unwanted immune responses."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology