Roche announced that a phase II study of its investigational treatment lebrikizumab, a humanized monoclonal antibody designed to block interleukin-13 (IL-13) cytokine, met its primary endpoint. In the study, lebrikizumab treatment resulted in a statistically significant increase in FEV1 (measure of lung function) in adults with asthma whose symptoms were inadequately controlled with inhaled corticosteriods (ICS). The overall frequency of adverse events was similar in both the placebo and the treatment group. The results of this study, known as ‘MILLY’, are being published in the New England Journal of Medicine (NEJM) today.

IL-13 is a key contributor to the features of asthma and increases periostin, a protein which can be measured with a blood test. In the study, patients with high pre-treatment periostin levels had greater improvement in lung function with lebrikizumab compared to patients with low periostin levels.

“The findings of the MILLY study, and the development of a potential biomarker, have shown that we may be able to select appropriate asthma patients for lebrikizumab therapy,” said Richard Scheller, Executive Vice President, Genentech Research and Early Development (gRED). “These results support further investigation of lebrikizumab as a personalized medicine for patients who suffer from moderate to severe uncontrolled asthma.”

The study also showed a trend towards a lower rate of severe asthma attacks (known as exacerbations) in patients treated with lebrikizumab, although the study was not powered to detect a reduction of these. These data are encouraging as severe asthma attacks, characterized by shortness of breath and chest tightness, are potentially life threatening.

Lebrikizumab may benefit patients with a high unmet medical need who have uncontrolled asthma with existing treatment options.

Lebrikizumab, which was developed by Genentech Research and Early Development, is a treatment being investigated for patients with uncontrolled asthma. It is a humanized monoclonal antibody designed to block the IL-13 cytokine (proteins that serve as messengers between cells) and reduce inflammation in the lung. IL-13 overexpression results in airway inflammation which is a feature of asthma.

The MILLY trial (a global phase II randoMized, double blInd, placebo-controLled study to evaLuate the safetY, tolerability and efficacy of lebrikizumab in adult patients with asthma who are inadequately controlled on inhaled corticosteroids) is a Roche/Genentech sponsored study to evaluate the safety profile, tolerability and efficacy of lebrikizumab in adult patients whose asthma is inadequately controlled on inhaled corticosteroids, a common treatment for asthma. Lebrikizumab was dosed every 28 days subcutaneously at 250mg, for a total of six doses. A total of 219 patients were randomized, one patient was not treated. 106 patients were randomized to lebrikizumab and 112 patients were randomized to placebo.

The primary endpoint of the study was a measure of lung function called the ‘pre-bronchodilator Forced Expiratory Volume 1 (FEV1)’. FEV1 is the volume of air that can be forced out in one second after taking a deep breath.

The primary endpoint of the trial showed that at week 12, lebrikizumab-treated patients had a 5.5% (95% CI, 0.8% to 10.2%; P=0.02) greater increase in pre-bronchodilator FEV1, from baseline than placebo-treated patients (lebrikizumab, 9.8%±1.9%; placebo, 4.3%±1.5%). Lebrikizumab-treated patients in the high-periostin subgroup experienced an 8.2% (P=0.03) relative increase from baseline FEV1, compared with placebo. Lebrikizumab treated patients in the low-periostin subgroup experienced a 1.6% (P=0.61) relative increase in FEV1, compared with placebo. Periostin was measured in serum using a protein assay.

Secondary pre-specified outcomes included the rates of protocol-defined exacerbations and severe exacerbations (worsening of asthma) through week 24. Although the study was not powered to detect a reduction of exacerbations, there was a trend towards a lower rate of severe exacerbation in patients treated with lebrikizumab.

The overall frequency of adverse events was similar in both the placebo and the treatment groups. Serious adverse events (SAEs) were observed in 4 lebrikizumab treated patients; 2 events of patients experiencing an asthma attack, community acquired pneumonia and traumatic pneumothorax (a collection of air inside the chest, between the lung and inner chest wall, which causes the lung to collapse) related to a car accident.

The most common side effects were infections (lebrikizumab 48.1%, placebo 49.1%), which included upper respiratory infections (lebrikizumab 12.3%, placebo 14.3%) and sinus infections (lebrikizumab 9.4%, placebo 8.0%). The overall frequency of adverse events was similar in both treatment groups (lebrikizumab, 74.5%; placebo, 78.6%), as were the frequencies of serious adverse events (lebrikizumab, 3.8%; placebo, 5.4%). Musculoskeletal events were more common with lebrikizumab (lebrikizumab, 13.2%; placebo, 5.4%). Twenty-five patients (11.5%) discontinued the study early, including 12 placebo and 13 lebrikizumab-treated patients.

Asthma is a chronic disease of the airways that makes breathing difficult and is a major public health problem affecting millions of people worldwide. A feature of asthma is inflammation of the air passages resulting in a variable airflow to the lungs. This results in recurrent attacks of coughing, wheezing, shortness of breath, and chest tightness thus requiring continuous medical care. Therapies such as inhaled corticosteroids are intended to ease airway inflammation and airway narrowing. Despite treatment with inhaled glucocorticosteroids (ICS), many patients continue to have uncontrolled asthma that requires the use of more intensive therapy.