PHOENIX — Exacerbation-prone asthma patients who had high blood eosinophil counts or elevated fractional exhaled nitric oxide (FeNO) appeared to benefit from lebrikizumab, pooled data from two disappointing phase III trials suggested.
In the post-hoc analysis of LAVOLTA I and LAVOLTA II, patients with at least one exacerbation in the prior year who had high blood eosinophil counts (≥300 cells/μL) saw a 38-41% reduction in their annualized exacerbation rate with two lebrikizumab doses as compared to placebo (P<0.001), reported Ellen Sher, MD, of Rutgers Robert Wood Johnson Medical School of Medicine in New Brunswick, New Jersey.
The story was the same for the subgroup of patients with a past-year exacerbation and elevated FeNO levels (≥50 ppb), which saw a 45-47% reduction in the annual exacerbation rate versus placebo (P<0.001), Sher said during her oral presentation at the annual meeting of the American Academy of Allergy, Asthma & Immunology.
The LAVOLTA studies were aimed at showing improvement in all-comers with uncontrolled asthma, but the trials failed to demonstrate “consistently significant results” for the primary endpoint of annualized exacerbation rate or a clear dose response, Sher explained.
In studies of atopic dermatitis involving higher doses of lebrikizumab, there was a clear dose-response curve, however, said Sher, suggesting that patients in the LAVOLTA trials may have been underdosed (they received doses of 37.5 mg or 125 mg every 4 weeks).
Sher suggested that future trials in asthma should involve higher lebrikizumab doses and target exacerbation-prone patients with type 2 inflammation, as defined by appropriate biomarkers.
“Certainly, we have to realize that this study with lebrikizumab was a post-hoc analysis, and there are limitations with that,” Roxana Siles, MD, of the Cleveland Clinic in Ohio, told MedPage Today. “We definitely need a direct clinical trial that targets these specific groups of patients — those with high levels of nitric oxide and blood eosinophils.”
Siles, who was not involved in the trials, called these subgroup results “striking,” and said the final chapter for lebrikizumab in uncontrolled asthma has not been written.
“These findings tell me that lebrikizumab could be a great product in a select group of patients,” she said. “This drug worked well in atopic dermatitis, so we know the mechanism of action is there.”
Testing for eosinophil and FeNO is already part of a general workup for asthma patients, Siles noted. “When we use these biologic agents in treating asthma, we do run tests to determine what biomarkers are present so that we can match the right patient to the right drug.”
Overall, LAVOLTA I and LAVOLTA II assigned 716 patients to each dose of lebrikizumab and 716 people to placebo.
For the subgroup with at least one prior-year exacerbation and high blood eosinophil counts in the post-hoc analysis, 174 patients received 125 mg lebrikizumab, 187 received 37.5 mg lebrikizumab, and 183 patients received placebo.
For the subgroup with high FeNO levels, 107 patients were assigned 125 mg lebrikizumab, 105 were assigned 37.5 mg lebrikizumab, and 109 patients were assigned to placebo.
The study was supported by Eli Lilly.
Sher disclosed relationships with AstraZeneca, AbbVie, Aimmune, BioCryst, Boehringer Ingelheim, Eli Lilly, Genentech, GlaxoSmithKline, Regeneron, Sanofi, Optinose, Teva, ALK, Amgen, Allergy Therapeutics, Celgene, Merck, Menlo Therapeutics, Gossamer, Novartis, and Shionogi.
Siles disclosed relationships with DynaMed.