B32-42 Comparable Pharmacokinetics and Pharmacodynamics of Londamocitinib, an Inhaled, Selective JAK1 Inhibitor, When Administered via the Turbuhaler® or Genuair® Device in Participants With Mild Asthma

Introduction Londamocitinib (AZD4604) is an inhaled, selective JAK1 inhibitor in development for individuals with uncontrolled moderate-to-severe asthma. In clinical studies to date, londamocitinib has been administered via a Genuair dry powder inhaler (DPI); going forwards it is to be administered via the Turbuhaler DPI. This study was designed to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of londamocitinib delivered using the two devices. Methods This Phase 1b, multicentre, randomized, placebo-controlled, single-blinded study enrolled participants with mild asthma and elevated fractional exhaled nitric oxide (FeNO ≥40 ppb) (NCT06732882). Participants (n = 7 per arm) received 1400 µg londamocitinib or placebo twice daily via the Turbuhaler or Genuair device for 10 days. PK comparisons were performed after the last dose on Day 10; PD comparisons evaluated changes in FeNO from baseline to Day 10. Results Londamocitinib plasma exposures at steady state were comparable between devices. The mean ± standard deviation of the maximum plasma concentration (Cmax) was 15.45±5.64 nmol/L vs 14.78±3.80 nmol/L and area under the curve limited to the last sampling time point (AUClast) was 46.52±16.52 h*nmol/L vs 46.19±13.42 h*nmol/L (Turbuhaler and Genuair respectively) (Figure 1). The relative FeNO reduction at Day 10 compared to placebo was not meaningfully different between devices (51% Turbuhaler vs 59% Genuair). Londamocitinib showed acceptable safety and tolerability with both devices, with no severe treatment-related adverse events. Conclusion Londamocitinib has comparable PK and PD profiles when administered via Turbuhaler and Genuair in participants with mild asthma, supporting device transition in future londamocitinib studies. These findings are consistent with prior Phase 1 PK/PD data obtained with Genuair. Figure 1 Pharmacokinetics of londamocitinib: Geometric mean plasma concentration (nmol/L) over time at Day 10 This abstract is funded by: AstraZeneca