AT 2016 AAAAI ANNUAL MEETING
LOS ANGELES (FRONTLINE MEDICAL NEWS) – The investigational interleukin-13 inhibitor lebrikizumab provides a clinically meaningful improvement in measures of lung function within 1 week after the first dose in patients with moderate-to-severe uncontrolled asthma on standard-of-care therapy and a high baseline serum periostin level, Dr. Jonathan Corren reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.
He presented a post hoc analysis of three phase II randomized trials of lebrikizumab as add-on therapy in a total of 558 patients with uncontrolled asthma while on a moderate- or high-dose inhaled corticosteroid plus at least one other controller medication, most often a long-acting beta agonist. The post hoc analysis included 333 asthma patients who received lebrikizumab subcutaneously at 125 or 250 mg every 4 weeks for 12 weeks and 225 who got placebo. Baseline serum periostin levels were 50 ng/mL or higher in 252 participants.
One week after the first dose of lebrikizumab, the high serum periostin group demonstrated a placebo-subtracted mean 147-mL improvement from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1). The week 1 improvement in FEV1 with lebrikizumab in the low serum periostin group was more modest: a placebo-subtracted 57 mL.
The response to lebrikizumab was maintained through 12 weeks of once-monthly therapy, with a mean placebo-subtracted week 12 improvement in FEV1 of 198 mL in the high-periostin group, compared with 74 mL in low-periostin patients. The lebrikizumab-treated group with high baseline periostin had a 16% improvement from baseline in FEV1 as compared with a 5% improvement in placebo-treated patients with high periostin.
The three trials were known by the acronyms MILLY, LUTE, and VERSE. Dr. Corren was first author of the MILLY study (N Engl J Med. 2011 Sep 22;365(12):1088-98), which was the initial report that lebrikizumab performed markedly better in patients with uncontrolled asthma and a high baseline serum periostin – a biomarker for IL-13 activity – and that periostin was a better predictor of response to lebrikizumab than either blood eosinophil count or serum IgE.
The new pooled post hoc analysis was performed to boost sample size and confirm the key MILLY findings, as well as to more closely examine the speed of improvement in airflow in response to therapy, said Dr. Corren of the University of California, Los Angeles.
Lebrikizumab is an IgG4 humanized monoclonal antibody that binds to IL-13 with high affinity. Its efficacy in the phase II trials confirms the importance of IL-13 as a mediator of disease activity in a subset of asthma patients with activation of Type 2 lymphocytes.
“We know specifically that IL-13 has some very important effects in asthma, including upregulation of adhesion molecules that allow eosinophils to stick in the lung, as well as promoting hyperplasia of smooth muscle and mucus cell hyperplasia with increased mucus secretion. Immunologically, it allows switching from IgM to IgE on the surface of B cells. So IL-13 is a cytokine that literally makes people atopic,” Dr. Corren explained in an interview.
Several ongoing phase III randomized trials of lebrikizumab in adults with uncontrolled asthma despite standard-of-care therapy are due to be completed in the first half of 2017. A phase III trial in adolescents is also underway.
Dr. Corren reported receiving research funding from Roche/Genentech, which sponsored the studies.