AstraZeneca PLC (AZN.US) has received approval from China's Center for Drug Evaluation (CDE) for clinical trials of its new Class 1 drug, AZD1163 injection, intended for the treatment of rheumatoid arthritis. AZD1163 is a novel bispecific antibody designed to inhibit the activity of extracellular peptidylarginine deiminase (PAD) enzymes 2 and 4, which are responsible for protein citrullination in rheumatoid arthritis (RA) patients. In susceptible individuals, citrullinated proteins activate a cascade of T-cell-driven events that promote B-cell maturation and activation, leading to the production of pathogenic anti-citrullinated protein antibodies (ACPA). ACPA is associated with poorer prognosis, often manifesting as more severe joint damage and rapidly progressing disease.

In vitro experiments have demonstrated that AZD1163 can inhibit protein citrullination and elevated PAD activity present in the serum and synovial fluid of RA patients. Initial data from a study presented at the 2025 ACR Annual Meeting evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD1163 in healthy volunteers, including its effect on systemic PAD enzyme activity. The study showed that exposure to AZD1163 increased in a dose-proportional manner, with peak concentrations observed on day 10 following subcutaneous administration. The estimated bioavailability for subcutaneous delivery was 65%. The mean systemic clearance rate was 0.15 liters per day, and the mean elimination half-life was 38 days.

Significant, dose-dependent inhibition of PAD2/4 activity was observed, with a maximum inhibition rate exceeding 95%, confirming target engagement. The incidence of anti-drug antibodies (ADA) among AZD1163 recipients was low, at 6.7%. Adverse events were infrequent, and the drug was well-tolerated across escalating doses. This first-in-human study of a novel bispecific antibody inhibiting PAD2/4 enzymes indicates that AZD1163, administered every two weeks, was well-tolerated in healthy volunteers and exhibited favorable pharmacokinetic profiles across the studied dose range. Target engagement was further demonstrated by the inhibition of PAD2/4 activity in ex vivo plasma. The results from this Phase 1 study support further evaluation of AZD1163 in RA patients.

According to ClinicalTrials.gov, AstraZeneca is currently conducting a Phase 2 clinical study of AZD1163 for the treatment of rheumatoid arthritis patients. The recent clinical trial approval in China indicates that clinical research for the product is set to commence in the country.