The following article is a part of conference coverage from the American Academy of Allergy, Asthma & Immunology Annual Meeting, being held in Phoenix, Arizona, from February 25 to 28, 2022. The team at Pulmonology Advisor will be reporting on the latest news and research conducted by leading experts in the field. Check back for more from the AAAAI 2022 Virtual Annual Meeting.
Patients with a history of asthma exacerbations in the previous year and elevated type 2 (T2) biomarkers who were treated with the monoclonal antibody lebrikizumab (LEB) exhibited a significant reduction in exacerbations. These were among the findings of a post-hoc analysis of the duplicate placebo-controlled, phase 3 LAVOLTA I and LAVOLTA II trials of patients with moderate to severe asthma. Results of the analysis are being presented at the American Association of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting, held in Phoenix, Arizona, from February 25 to 28.
LAVOLTA I and LAVOLTA II enrolled patients regardless of their asthma exacerbation history, baseline blood eosinophila, or fractional exhaled nitric oxide (FeNO) level, with 2 dose groups evaluated: LEB 125 mg every 4 weeks or LEB 37.5 mg every 4 weeks. The primary study endpoint was the adjusted exacerbation rate ratio (AERR) in T2-positive patients, which was defined as having periostin levels of at least 50 ng/mL or blood eosinophils (eos) of at least 300 cells/µL. Results of both LAVOLTA I and LAVOLTA II failed to demonstrate consistently significant results in AERR or a dose response.
The current post-hoc analysis established AERR for LEB vs placebo from the LAVOLTA I and LAVOLTA II trials in subpopulations of patients with at least 1 exacerbation in the previous 12 months. Patients were grouped and analyzed according to their baseline levels of FeNO (≤25 ppb, ≥25 to <50 ppb, or ≥50 ppb) and eosinophilia (eos <150 cells/µL, ≥150 to <300 cells/µL, or ≥300 cells/µL).
Results of the study showed that LEB reduced AERR vs placebo in combined LAVOLTA I and LAVOLTA II trials as follows: (1) FeNO ≤25 ppb (LEB 125 mg: 0.79; 95% CI, 0.62- 1.01; LEB 37.5 mg: 0.75; 95% CI, 0.58-0.96); (2) FeNO ≥25 to <50 ppb (LEB 125 mg: 0.83; 95% CI, 0.63-1.07; LEB 37.5 mg: 0.70; 95% CI, 0.53 to 0.92); (3) FeNO ≥50 ppb (LEB 125 mg: 0.55; 95% CI,0.41-0.72; LEB 37.5 mg: 0.53; 95% CI, 0.40 to 0.69);
(4) eos <150 cells/µL (LEB 125 mg: 0.94; 95% CI, 0.68 -1.29; LEB 37.5 mg: 0.57; 95% CI, 0.40-0.82); (5) eos ≥150 to <300 cells/µL (LEB 125 mg: 0.75; 95% CI, 0.56-0.99); LEB 37.5 mg: 0.76; 95% CI, 0.57-1.02), (6) eos ≥300 cells/µL (LEB 125 mg: 0.62; 95% CI, 0.50 to 0.76; LEB 37.5 mg: 0.59; 95% CI, 0.48 to 0.73).
The investigators concluded that LAVOLTA study participants with a history of prior-year asthma exacerbations and elevated T2 biomarkers did experience significantly fewer exacerbations, and that future studies are needed with optimal targeting of LEB in patients with exacerbation-prone T2 inflammation.
Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.
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Sher E, Korenblat P, Brusselle G, et al. Post-hoc analysis of lebrikizumab phase 3 trials (LAVOLTA I and II): enhanced efficacy in patients with prior exacerbations and elevated baseline FENO or blood eosinophilia. Presented at: American Academy of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting; February 25–28, 2022; Phoenix, AZ. Abstract 191.