New study confirms long-term safety and efficacy of ozoralizumab in rheumatoid arthritis patients

A recent study published in Rheumatic and Musculoskeletal Diseases (RMD) Open has demonstrated the long-term safety and efficacy of ozoralizumab, a novel anti-TNF multivalent variable domain of heavy-chain (VHH) antibody, in patients with rheumatoid arthritis (RA). The findings, based on an integrated analysis of the OHZORA, NATSUZORA, and HOSHIZORA trials, offer promising prospects for rheumatologists exploring extended treatment options for RA. 

The study enrolled 521 patients across the OHZORA and NATSUZORA trials, with 401 progressing to the HOSHIZORA trial. Ultimately, 279 patients completed the long-term extension, with a mean treatment duration of 200 weeks and a total exposure of 1419.34 PY. Of the participants, 96.9% experienced at least one AE, though the majority were mild to moderate in severity. Importantly, no significant AEs emerged during the study, and there were no specific safety concerns regarding AESIs, despite one reported death. Remarkably, ozoralizumab maintained American College of Rheumatology (ACR) response rates of 20%, 50%, and 70% throughout the trials, demonstrating its sustained effectiveness over the long term. The study highlighted the absence of new safety concerns and affirmed ozoralizumab’s consistent efficacy in treating RA over a mean treatment duration of 200 weeks. This extended data underscores the potential of ozoralizumab as a valuable long-term treatment option for RA, particularly in the growing field of biological disease-modifying antirheumatic drugs (bDMARDs). 

Ozoralizumab is a next-generation anti-TNF antibody, weighing 38 kDa, comprised of two humanized antihuman TNF variable heavy-chain domains (VHH) and one humanized antihuman serum albumin (HSA) VHH. VHH antibodies are derived from a unique class of heavy-chain-only antibodies naturally produced by llamas and other camelid species. Ozoralizumab has shown strong inhibitory activity against human TNF and demonstrated a specific binding affinity for HSA. This interaction neutralizes TNF activity and extends the serum half-life of the drug by binding it to serum albumin. The efficacy and safety of ozoralizumab have been previously demonstrated in patients with active rheumatoid RA, both in combination with methotrexate (MTX) in the OHZORA trial and without MTX in the NATSUZORA trial. Data from the long-term extension HOSHIZORA trial further supported these results. 

The study findings may influence future research and clinical practices by reinforcing the role of ozoralizumab as a reliable treatment for long-term use in RA management. The absence of significant safety concerns, combined with the maintenance of efficacy rates, positions ozoralizumab as a promising candidate for managing RA. This offers hope for sustained disease control in patients requiring long-term intervention. 

 Reference 

  1. Tanaka Y, Miyazaki Y, Kawanishi M, Yamasaki H, Takeuchi T. Long-term safety and efficacy of anti-TNF multivalent VHH antibodies ozoralizumab in patients with rheumatoid arthritis. RMD Open. 2024 Aug 22;10(3):e004480. 
  2. Takeuchi T, Kawanishi M, Nakanishi M, Yamasaki H, Tanaka Y. Phase II/III Results of a Trial of Anti-Tumor Necrosis Factor Multivalent NANOBODY Compound Ozoralizumab in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2022 Nov;74(11):1776-1785. 
  3. Tanaka Y, Kawanishi M, Nakanishi M, Yamasaki H, Takeuchi T. 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). Mod Rheumatol. 2023 Aug 25;33(5):875-882. 
  4. Tanaka Y, Kawanishi M, Nakanishi M, Yamasaki H, Takeuchi T. 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). Mod Rheumatol. 2023 Aug 25;33(5):883-890.