SAN DIEGO — Lebrikizumab, a novel monoclonal antibody against the inflammatory cytokine IL-13, might have reduced exacerbations in severe asthma in a randomized trial, although manufacturing problems undermined any conclusions.
Overall, the monthly injections cut asthma exacerbations a relative 36% compared with placebo (0.68 versus 0.43 per year), Nicola Hanania, MD, of Baylor College of Medicine in Houston, showed in combined analysis of the LUTE and VERSE trials.
But that effect missed statistical significance and had to be extrapolated from a variable follow-up period of a median 24 to 28 weeks of the 52 as originally planned in what were to be the pivotal phase III trials.
During the trials, “a process-related impurity” necessitated a change to manufacturing and brought dosing to a halt at just 463 of a planned 1,400 patients, Hanania reported here at the American Academy of Allergy, Asthma, and Immunology meeting.
Sponsors Genentech and Roche downgraded LUTE and VERSE to phase IIb and have started a new set of pivotal trials, LAVOLTA I and II.
“It would have been nice to see the study completed,” commented Wesley Burks, MD, of the University of North Carolina at Chapel Hill. “But certainly there’s a difference in those that were treated and not treated to suggest that it might work.”
The nearly half of patients with high levels of the IL-13 marker periostin saw a significant 60% relative reduction in exacerbations with lebrikizumab compared with placebo. Lung function improvements were significant for that group as well.
Biologics are making their way into allergy and asthma now that agents can be narrowly targeted, said Burks, a past AAAAI president.
Other less specifically-targeted agents had been tried before but not been very effective, he told MedPage Today.
“To me this is the second-generation of monoclonal antibodies,” he said. “They’re able to target more specific targets that aren’t general targets that have effects in other cells. To be able to target cytokines or cytokine receptors, IL-5, IL-13, that are specific for allergic disease, that’s the big deal about it.”
The drug is also being investigated for idiopathic pulmonary fibrosis.
Serious adverse events weren’t elevated with the drug. There were no cases of anaphylaxis, serious hypersensitivity, or deaths, either.