Lebrikizumab Reduces Asthma Attack Rate in Mid-Stage Trials
Improved lung function linked to periostin biomarker
New findings have been reported from two phase IIb studies investigating lebrikizumab (Roche) in patients with severe uncontrolled asthma. The data showed that asthma attacks were reduced by 60% in lebrikizumab-treated patients with a high level of the biomarker periostin, compared with a reduction of only 5% in patients with a low level of periostin.
The data also showed that, in patients with high periostin levels, lebrikizumab improved lung function, as measured by the forced expiratory volume at 1 second (FEV1).
Findings from the phase IIb LUTE and VERSE trials were presented March 5 at the annual meeting of the American Academy of Allergy, Asthma, and Immunology in San Diego, California.
The new data build on previous positive phase II findings related to lebrikizumab treatment in patients who were uncontrolled despite the use of inhaled corticosteroids (ICS). The LUTE and VERSE studies enrolled a more severe asthma population, as these patients were receiving high-dose ICS in addition to a second asthma controller therapy.
Based on the previous phase II results, lebrikizumab is currently being evaluated in adult patients with severe uncontrolled asthma in two phase III studies (LAVOLTA I and LAVOLTA II). Lebrikizumab is also under investigation in seven ongoing or planned clinical studies, including one for idiopathic pulmonary fibrosis.
LUTE and VERSE were replicate double-blind studies that randomly assigned patients with severe uncontrolled asthma (despite treatment with ICS and a second controller) to receive lebrikizumab (37.5 mg, 125 mg, or 250 mg) or placebo subcutaneously every 4 weeks. Both studies, initially phase III, were converted to phase IIb upon identification of a process-related impurity requiring changes to the lebrikizumab manufacturing process.
The primary endpoint of both studies was the rate of exacerbations during the placebo-controlled period. The data were evaluated separately in patients with low and high periostin levels. The data showed that asthma attacks were reduced by 60% in lebrikizumab-treated patients with a high level of periostin (≥ 50 ng/mL; P = 0.01 all doses combined), compared with a reduction of only 5% in patients with a low level of periostin (≤ 50 ng/mL; P = 0.87 all doses combined). Specifically, exacerbation rates were reduced by 22%, 77%, and 81% in periostin-high patients treated with lebrikizumab 250 mg, 125 mg, and 37.5 mg, respectively.
The change from baseline in FEV1 was a key secondary endpoint. At 12 weeks in the periostin-high group, there was a 9.1% percent increase in FEV1 in the pooled lebrikizumab arms over placebo (P = 0.02), compared with a 2.6% increase over placebo in the periostin-low group (P = 0.26).
The data showed that FEV1 was increased by 6.8%, 10.7%, and 10.1% in the periostin-high patients treated with lebrikizumab 37.5 mg, 125 mg, and 250 mg, respectively, compared with placebo.
The overall frequency of adverse events was 70% in the lebrikizumab arm (all dose levels combined) compared with 63% in the placebo group. The frequencies of serious adverse events were similar (lebrikizumab, 2.0%; placebo, 1.7%). Overall, no clinically important safety signals were identified.
Lebrikizumab is a novel humanized monoclonal antibody designed to specifically block the action of interleukin-13 (IL-13), a cytokine that contributes to airway inflammation and the asthma disease process in some patients. The biomarker periostin may predict benefit from anti–IL-13 therapy.
Periostin is a protein that has been identified as a key biomarker (measured with a blood test) in certain types of asthma. In asthma patients with higher levels of periostin, IL-13 appears to be a major contributor to their airway inflammation. In the new phase II trials, periostin was a prespecified biomarker in the primary endpoint. Periostein has been shown to be a predictor of airway eosinophilia — a prominent feature of asthma — and has potential value in selecting patients for treatment with lebrikizumab.
Source: Roche; March 5, 2014.