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

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

Efficacy and pharmacokinetics of ozoralizumab, an anti-TNFα NANOBODY compound, in patients with rheumatoid arthritis: 52-week results from the OHZORA and NATSUZORA trials. (PubMed, Arthritis Res Ther) - "OZR showed a long half-life and favorable PK properties. A post hoc analysis suggested sustained efficacy independent of trough concentration by subcutaneous administration of OZR 30 mg at 4-week intervals for 52 weeks."

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

Safety and Efficacy of New TNF Blocker Ozoralizumab (JCR 2023) - "Co-sponsored by: Taisho Pharmaceutical Co., Ltd."

Clinical

Antibodies to watch in 2023. (PubMed, MAbs) - "As of mid-November, 12 antibody therapeutics had been granted first approvals in either the United States or European Union (tebentafusp (Kimmtrak), faricimab (Vabysmo), sutimlimab (Enjaymo), relatlimab (Opdualag), tixagevimab/cilgavimab (Evusheld), mosunetuzumab (Lunsumio), teclistamab (TECVAYLI), spesolimab (SPEVIGO), tremelimumab (Imjudo; combo with durvalumab), nirsevimab (Beyfortus), mirvetuximab soravtansine (ELAHERE™), and teplizumab (TZIELD)), including 4 bispecific antibodies and 1 ADC...An additional seven were first approved in China or Japan in 2022, including two bispecific antibodies (cadonilimab and ozoralizumab)...Our data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline grew by ~20% in the past year to include nearly 140 investigational antibody therapeutics that were designed using a wide variety of formats and engineering techniques. Of those in late-stage development, marketing application submissions for..."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Ozoralizumab: First Approval. (PubMed, Drugs) - "In September 2022, ozoralizumab was approved in Japan for the treatment of RA that is inadequately managed by current available treatments. This article summarizes the milestones in the development of ozoralizumab leading to this first approval."

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

A novel anti-TNF-α drug ozoralizumab rapidly distributes to inflamed joint tissues in a mouse model of collagen induced arthritis. (PubMed, Sci Rep) - "To elucidate the mechanism underlying the rapid onset of the effects of ozoralizumab, we compared the biodistribution kinetics of ozoralizumab and adalimumab after subcutaneous injection in an animal model of arthritis. These results indicate that ozoralizumab enters the systemic circulation more rapidly and is distributed to the target tissues earlier and at higher levels than conventional IgG antibodies. Our investigation provides new insight into the mechanism underlying the rapid onset of the effects of ozoralizumab in clinical practice."

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

Efficacy and safety of anti-TNF multivalent NANOBODY® compound 'ozoralizumab' without methotrexate co-administration in patients with active rheumatoid arthritis: A 52-week result of phase III, randomised, open-label trial (NATSUZORA trial). (PubMed, Mod Rheumatol) - "Ozoralizumab, at 30 and 80 mg, demonstrated significant therapeutic effects without MTX, and the efficacy was maintained for 52 weeks with active RA. Ozoralizumab showed an acceptable tolerability profile over 52 weeks."

Journal • P3 data • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Efficacy and safety of the anti-TNF multivalent NANOBODY® compound ozoralizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: A 52-week result of a phase II/III study (OHZORA trial). (PubMed, Mod Rheumatol) - "Ozoralizumab demonstrated significant therapeutic effects and efficacy, which was maintained for 52 weeks. The safety profile was consistent with the evaluated results in interim analysis at week 24, and ozoralizumab was well-tolerated up to week 52."

Journal • P2/3 data • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology