Astrazeneca PLC Sponsored ADR (AZN.US) dual anti-1 class new drug approved for clinical use in China.

Recently, the official website of the China National Medical Products Administration Drug Evaluation Center (CDE) publicized that the 1st category new drug injection AZD1163 sponsored by Astrazeneca PLC Sponsored ADR (AZN.US) has been approved for clinical trials, aiming to develop a treatment for rheumatoid arthritis. It is reported that AZD1163 is a novel bispecific antibody that can inhibit the activity of peptidyl arginine deiminase (PAD) 2 and 4 in the extracellular matrix, which are responsible for protein citrullination in patients with rheumatoid arthritis (RA). In susceptible individuals, citrullinated proteins can activate a series of events driven by T lymphocytes, promoting the maturation and activation of B cells, resulting in the production of pathogenic anti-citrullinated protein antibodies (ACPA). ACPA is associated with a worse prognosis, often manifesting as more severe joint damage and rapid disease progression. In in vitro experiments, AZD1163 was able to inhibit protein citrullination and elevated PAD activity present in the serum and synovial fluid of RA patients. At the 2025 ACR annual meeting, the safety, tolerability, pharmacokinetics, and pharmacodynamic data research of AZD1163 in healthy volunteers and its effect on systemic PAD enzyme activity were first disclosed. The study showed that the exposure of AZD1163 increased in a dose-proportional manner, with peak concentrations occurring on the 10th day after subcutaneous administration. The estimated bioavailability after subcutaneous administration was 65%. The average systemic clearance rate was 0.15 L/day, with an average elimination half-life of 38 days. Significant and dose-dependent inhibition of PAD2/4 activity was observed, with a maximum inhibition rate of over 95%, confirming target binding. The occurrence of anti-drug antibodies (ADA) in AZD1163 recipients was low at 6.7%. Adverse events were minimal, and dose escalation was well tolerated. This first human study of the novel bispecific antibody targeting PAD2/4 enzymes demonstrated good tolerability of AZD1163 administered every two weeks in healthy volunteers, showing favorable pharmacokinetic characteristics within the studied dose range. Target binding was confirmed through the inhibition of PAD2/4 activity in ex vivo plasma. The results obtained from this phase 1 study support further evaluation of AZD1163 in RA patients. According to the ClinicalTrials website, Astrazeneca PLC Sponsored ADR is conducting a Phase 2 clinical study of AZD1163 for the treatment of rheumatoid arthritis patients. The approval for clinical trials in China for this product indicates that clinical research will soon be conducted in China.