AZD8630/AMG 104, an inhaled anti-thymic stromal lymphopoietin antibody fragment, for moderate-to-severe asthma: Phase 1 randomized controlled trial

  • J Allergy Clin Immunol. 2026 Apr 20:S0091-6749(26)00262-9. doi: 10.1016/j.jaci.2026.03.026.
Sarah R Doffman  1 ,  Davinder P S Dosanjh  2 ,  Muhammad Waqas Sadiq  3 ,  Yuko Matsunaga  4 ,  Jason D Cooper  5 ,  Geoff Edwards  5 ,  Sara Asimus  3 ,  Lubna Abuqayyas  6 ,  Xiao-Hong Zhou  7 ,  Ian C Scott  8 ,  Mathias Cardner  9 ,  Jane R Parnes  10 ,  Kristina Kovacina  11 ,  Nicholas White  12 ,  Michael G Cushion  13 ,  Maria G Belvisi  14 ,  Dinesh Saralaya  15 ,  Thomas Brown  16 ,  Jutta Beier  17 ,  Nestor A Molfino  4
Affiliations
  • 1. Clinical Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, Mass. Electronic address: [email protected].
  • 2. Clinical Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, Mass; Birmingham Acute Care Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
  • 3. Clinical Pharmacology and Quantitative Pharmacology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • 4. Global Development, Inflammation, R&D, Amgen Inc., Thousand Oaks, Calif.
  • 5. Biometrics and Statistical Innovation, BioPharmaceuticals R&D, AstraZeneca, Cambridge, Mass.
  • 6. Clinical Pharmacology Modeling and Simulation, Amgen, Cambridge, Mass.
  • 7. Patient Safety Biopharma, Chief Medical Office, Oncology R&D, AstraZeneca, Gothenburg, Sweden.
  • 8. Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, Mass.
  • 9. Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • 10. Early Development, Amgen Inc., Thousand Oaks, Calif.
  • 11. Bioanalysis, AstraZeneca, San Francisco, Calif.
  • 12. Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, Mass.
  • 13. Clinical Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, Mass.
  • 14. Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; Respiratory Pharmacology, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
  • 15. Respiratory Medicine, Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom.
  • 16. Respiratory Medicine, Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom.
  • 17. Insaf Respiratory Research Institute, Taunusstein, Germany.
PMID: 42019634 DOI: 10.1016/j.jaci.2026.03.026
Abstract

Background: AZD8630/AMG 104 is an inhaled anti-thymic stromal lymphopoietin (TSLP) antibody fragment in development for the treatment of patients with moderate-to-severe asthma.

Objective: We sought to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and target engagement of AZD8630/AMG 104 in healthy adults and adults with moderate-to-severe asthma.

Methods: This was a first-in-human, 2-part, phase 1 study of AZD8630/AMG 104. Part A was a single-blind study in healthy adults evaluating single and multiple ascending doses (0.2-16 mg) inhaled once daily for up to 14 days; part B was a double-blind, randomized, placebo-controlled study in adults with moderate-to-severe asthma and elevated fractional exhaled nitric oxide (Feno; ≥30 ppb) randomized to AZD8630/AMG 104 (0.4, 2, and 8 mg) or placebo once daily for 28 days. The primary objective was safety and tolerability. Secondary and exploratory objectives included pharmacokinetics, immunogenicity, pharmacodynamics (change from baseline in Feno), and target engagement.

Results: In total, 181 participants (part A, n = 104; part B, n = 77) were randomized. AZD8630/AMG 104 showed an acceptable safety profile, with low incidence of treatment-induced antidrug antibodies (part A, n = 1; part B, n = 2), and dose-dependent pharmacokinetics. In part B, there was a statistically significant reduction in Feno in AZD8630/AMG 104 8 mg recipients versus placebo (day 28, 23%; P = .037). AZD8630/AMG 104 dosing led to a dose-dependent decrease of free TSLP levels and increased TSLP-AZD8630/AMG 104 levels in serum in all participants.

Conclusion: AZD8630/AMG 104 was well tolerated, with pharmacokinetics suitable for once-daily dosing. Results demonstrate proof of mechanism: clinically meaningful reductions in Feno levels and evidence of target engagement. Further development of AZD8630/AMG 104 in adults with moderate-to-severe asthma is warranted.

Keywords
Asthma; fractional exhaled nitric oxide (Feno); inhaled biologics first-in-human; safety; thymic stromal lymphopoietin (TSLP).
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