LOS ANGELES—Early March brings with it post-hoc study results from two presentations at the recent American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting in Los Angeles—both of them related to asthma and from both sides of the pond, from London-based GlasoSmithKline (GSK) and from Ridgefield, Conn.-based Boehringer Ingelheim Pharmaceuticals Inc., the largest U.S. subsidiary of Germany’s Boehringer Ingelheim Corp. (BI).
GSK presented results from a post-hoc study which showed that severe asthma patients with a baseline blood eosinophil count of 150 cells/mL or above who received Nucala (100 mg fixed-dose subcutaneous injection of mepolizumab) or an investigational dose of mepolizumab had a significant improvement in their exacerbation rates compared to those receiving placebo. The data showed that when these patients were stratified by baseline eosinophil levels, a significant improvement in exacerbation rates was observed in all groups receiving mepolizumab (≥150, ≥300, ≥400, ≥500 cells/mL) with the greatest improvement occurring in those patients with higher levels of eosinophils.
The source of these data came from a meta-analysis of the DREAM (MEA112997) and MENSA (MEA115588) studies, encompassing a total of 1,192 patients, 846 of whom received mepolizumab and 346 on placebo. Overall, the meta-analysis demonstrated a 47-percent reduction in annual exacerbation rates with mepolizumab versus placebo. Clinically relevant reductions in exacerbation rate were shown to range from 52 percent for patients with a baseline eosinophil threshold of 150 cells/μL or above, to 70 percent for patients with a baseline eosinophil threshold of 500 cells/μL or above.
“In a sub-set of asthma patients, eosinophils drive airway inflammation. By utilizing eosinophils as a biomarker, we have been able to identify those asthma patients whose disease is severe and driven by the over-expression of eosinophils and are therefore likely to respond to treatment,” explained Steve Yancey, medicines development lead for mepolizumab at GSK. “This post-hoc analysis confirms the predictive nature of the relationship between baseline blood eosinophil counts and efficacy outcomes in patients treated with mepolizumab.”
The results of the meta-analysis reinforce the relevance of a data-driven approach to determining the eosinophil cut-off levels used to identify the patient population that is appropriate for treatment with mepolizumab—eosinophils are a type of white blood cell that play a role in the development of asthma. In people with asthma, inflammatory mediators released from the eosinophil cause inflammation in the lungs increasing the risk of an exacerbation.
Nucala is a monoclonal antibody that binds to IL-5, preventing it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this way reduces blood, tissue and sputum eosinophil levels. In the United States, Nucala is licensed as an add-on maintenance treatment for patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. Nucala is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus.
From BI’s American subsidiary came a presentation of new post-hoc analyses that show the addition of Spiriva Respimat to other asthma maintenance therapies helps improve lung function and asthma symptom control, while reducing asthma exacerbations (also known as flare-ups), independent of a patient’s subtype of allergic asthma. According to BI, these analyses evaluated the safety and efficacy of adding Spiriva Respimat to other maintenance therapies compared to placebo across the broad range of asthma patients studied, regardless of immunoglobulin E (IgE) or eosinophil levels.
The addition of Spiriva Respimat significantly improved lung function, according to the data. Adding Spiriva Respimat also was shown to improve asthma symptom control, as measured by the seven question Asthma Control Questionnaire (ACQ-7) and reduce the risk of asthma worsening and exacerbations. The ACQ-7 results in the pooled analysis did not distinguish among the treatment arms.
“The data confirm that adding Spiriva Respimat is a well-tolerated and effective treatment option for asthma patients independent of allergic subtype,” said Dr. Mark Vandewalker, director of Clinical Research of the Ozarks in Columbia, Mo. “For people with allergic asthma who are still experiencing symptoms, adding Spiriva Respimat may help open airways to improve breathing.”
Spiriva Respimat is steroid-free and is the first new class of inhaled medicine approved in over 10 years for asthma. The U.S. Food and Drug Administration (FDA) approved a once-daily dose of Spiriva Respimat 2.5 µg (delivered in 2 puffs of 1.25 µg each) for the long-term maintenance treatment of asthma in people ages 12 and older. Spiriva Respimat is not a treatment for sudden asthma symptoms. In the treatment of asthma, the maximum benefits in lung function may take up to four to eight weeks of dosing.
The post-hoc analyses are based on data from the two PrimoTinA-asthma and two MezzoTinA-asthma trials which are part of the UniTinA-asthma large-scale clinical trial program. The PrimoTinA-asthma trials investigated Spiriva Respimat as an add-on therapy for adults with asthma who continued to have symptoms despite taking at least ICS/LABA therapy. The MezzoTinA-asthma trials investigated Spiriva Respimat as an add-on therapy for adults with asthma who continued to have symptoms despite taking at least moderate-dose ICS therapy.
The safety and tolerability of Spiriva Respimat in each trial and treatment group were comparable with those of placebo in the overall patient population.