Genentech, a member of the Roche Group, recently reported top-line data from two Phase 3 clinical trials assessing the efficacy and safety of lebrikizumab in people with uncontrolled asthma despite standard-of-care treatment with an inhaled corticosteroid and a second controller medication.
The results obtained were disappointing given the previous data from Phase 2 trials.
The LAVOLTA I and LAVOLTA II Phase 3 trials were two multicenter, randomized, double-blind, placebo-controlled studies that together included more than 2,100 people across 28 countries. The primary endpoint of both trials was the rate of asthma exacerbations over a period of 52 weeks.
The results of the LAVOLTA I trial showed that treatment with lebrikizumab significantly reduced the rate of asthma exacerbations in people with higher levels of serum periostin or blood eosinophils, both airway inflammation biomarkers. There was also a significant improvement in lung function (assessed by forced expiratory volume in one second, called FEV1). However, the observed effects were inferior to the ones previously reported in Phase 2 trials assessing lebrikizumab.
In the LAVOLTA II trial, the exacerbation reduction did not meet statistical significance. There were no safety concerns reported in either trial.
“We were hopeful these identical studies would confirm the Phase II results because there is still a significant unmet need for people with severe asthma,” Sandra Horning, M.D., chief medical officer and head of Genentech’s Global Product Development, said in a press release. “These data require further interpretation, and analyses are ongoing to better understand the results and determine next steps.”
Data from the two trials will be submitted for presentation at upcoming medical meetings.
Asthma is expected to affect 400 million people worldwide by 2025. If uncontrolled, the condition causes substantial limitations on daily life, and in some cases it is fatal.
Lebrikizumab is a humanized monoclonal antibody and an experimental immunosuppressive drug for the treatment of asthma that cannot be adequately controlled with inhaled glucocorticoids. Lebrikizumab blocks interleukin 13 (IL-13), a cytokine (cell-signaling protein) that is produced by immune Th2 cells. IL-13 induces the expression of another signaling protein, called periostin, by epithelial cells of the bronchi. Periostin, in turn, seems to partake in a number of asthma-related problems, such as bronchial hyperresponsiveness, inflammation, and activation and proliferation of airway fibroblasts, which are involved in airway remodeling.