Phase 1 trial finds inhaled JAK1 inhibitor londamocitinib reduces Feno in mild asthma

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The Journal of allergy and clinical immunology Published April 6, 2026 Medically reviewed May 26, 2026 Study authors: Jellesmark Jensen Tina, Riff Camille, Lund Julia, Jevnikar Zala, Belvisi Maria G, Keen Christina, Mä… PubMed ↗ NCT04769869 ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Note: Phase 1 data show inhaled londamocitinib reduces Feno, a biomarker; clinical efficacy is unknown.

This first-in-human, phase 1 randomized controlled trial evaluated the inhaled selective JAK1 inhibitor londamocitinib (AZD4604) versus placebo. The study enrolled 85 healthy volunteers and 18 participants with mild asthma, primarily assessing safety, tolerability, pharmacokinetics, and target engagement over up to 10 days of follow-up.

In participants with mild asthma, londamocitinib at 1.4 mg and 3 mg doses led to an approximately 50% reduction in mean fractional exhaled nitric oxide (Feno), a marker of type 2 inflammation, after 3 days, with the effect persisting to day 10. The drug also showed suppression of IL-4-induced STAT6 phosphorylation in peripheral CD3 T cells, indicating systemic target engagement, though the extent was not quantified. The treatment was reported as well tolerated after single and multiple dosing, but specific adverse event rates were not reported.

Key limitations include the small sample size of participants with asthma (n=18), the early-phase design focused on biomarkers rather than clinical outcomes like symptom control or exacerbations, and the lack of reported safety event details. The study did not assess effects in severe asthma. Practice relevance is not established, as this is a preliminary safety and pharmacodynamic study. Further research is needed to determine the clinical efficacy and long-term safety profile of inhaled londamocitinib for asthma management.

Study Details

Study typeRct

Sample sizen = 85

EvidenceLevel 2

PublishedApr 2026

PMID41534719

TrialNCT04769869

View Original Abstract ↓

BACKGROUND: Janus kinase (JAK) 1 is a promising target for asthma treatment; it may address inflammation not controlled by inhaled corticosteroids. Londamocitinib (AZD4604) is a selective JAK1 inhibitor designed for inhaled delivery. OBJECTIVE: A 3-part randomized placebo-controlled phase 1 study (NCT04769869) was conducted in healthy volunteers (n = 85) and participants with mild asthma (n = 18) investigating safety, tolerability, pharmacokinetics, and lung and systemic target engagement of londamocitinib. METHODS: Single (0.025-6 mg) and multiple (0.4-3 mg, inhaled) doses of londamocitinib were administered to healthy volunteers and participants with mild asthma for up to 10 days. Effect on fractional exhaled nitric oxide (Feno), a type 2 inflammation marker, was assessed in participants with mild asthma with elevated Feno. RESULTS: Londamocitinib was well tolerated after single and multiple dosing. After inhalation, londamocitinib was quickly absorbed, and systemic exposure increased approximate dose proportionally. After twice-daily dosing to obtain steady state, 2- to 4-fold accumulation was observed. Approximately 50% reductions in mean Feno were seen for 1.4 and 3 mg doses of londamocitinib in participants with mild asthma after 3 days, which persisted to day 10 of dosing, versus no significant reduction with placebo. Transient, minimal suppression of systemic target engagement (IL-4-induced STAT6 phosphorylation in peripheral CD3 T cells) was seen with the 3 mg but not the 1.4 mg londamocitinib dose. CONCLUSION: Twice-daily administration of londamocitinib provides rapid and effective reduction of Feno in patients with mild asthma with elevated Feno.