Pharmacological and Safety Evaluation of AMG 139: A Human Anti-IL-23 Monoclonal Antibody for Inflammatory Diseases

AMG 139 is a monoclonal antibody that targets IL-23 and is currently undergoing a phase II clinical trial for the treatment of Crohn's disease. To enhance its clinical progress, various tests were carried out on cynomolgus monkeys, including in vitro assays and in vivo studies, to assess the drug's pharmacological profile, efficacy, and safety.

In the experimental phase, the drug's pharmacological effects, how it is absorbed and distributed in the body (pharmacokinetics), its impact on biological processes (pharmacodynamics), and potential toxicity were examined. The administration was done either intravenously or subcutaneously, weekly for a period of up to 26 weeks.

Key findings indicate that AMG 139 has a strong binding affinity to IL-23 in both humans and cynomolgus monkeys, effectively neutralizing IL-23's biological activity without affecting IL-12. Following a single dose, the drug showed linear pharmacokinetics with a subcutaneous bioavailability of 81% and an average half-life of 8.4 to 13 days. With weekly subcutaneous dosing over 3 to 6 months, the drug's exposure increased proportionally with the dose, and the accumulation between the first and last dose varied from 2 to 3.5 times.

There were no significant differences in immune cell profiling, T-cell responses, or bone formation markers between the test subjects receiving AMG 139 and those given a placebo. Additionally, no adverse effects were observed in terms of clinical signs, body weight, vital signs, eye health measures, clinical pathology, electrocardiogram readings, organ weights, or tissue pathology in monkeys administered the highest tested dose of AMG 139.

The results from the in vitro pharmacology, pharmacokinetics, immunogenicity, and safety studies in cynomolgus monkeys suggest that AMG 139 is a promising candidate for further clinical development for treating a range of inflammatory conditions.