Further Analysis of Pivotal Phase III Studies Show Reduction in Asthma Exacerbation Rates by at least half (50% and 59% respectively) and Significant Improvement in Lung Function in Patients Treated with Reslizumab
Teva Pharmaceutical Industries Ltd., (NYSE: TEVA) announced today that The Lancet Respiratory Medicine has published data from two replicate 52-week Phase III global studies on the company’s investigational anti-interleukin-5 (IL-5) monoclonal antibody, reslizumab. The data showed that treatment with reslizumab, compared to placebo, significantly reduced the annual rate of clinical asthma exacerbations (Study 1, 50% and Study 2, 59%), significantly improved lung function, and provided sustained improvement in multiple secondary measures of asthma control in patients with asthma and elevated blood eosinophils who were inadequately controlled on an inhaled corticosteroid (ICS)-based regimen. Findings from the studies were also presented today at the 2015 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in a late-breaking oral session.
“Results from these Phase III studies highlight the importance of phenotype-targeted therapies and represent a potential change in the treatment paradigm for patients with moderate-to-severe asthma and elevated blood eosinophil levels who are uncontrolled on an ICS-based therapy,” said Professor Mario Castro, Washington University School of Medicine, Division of Pulmonary and Critical Care Medicine and lead investigator. “If approved, reslizumab could provide doctors with a new treatment option that has the potential to both significantly reduce patients’ asthma exacerbations and improve their current symptom control and lung function.”
Across both trials, a total of 953 patients with asthma and elevated blood eosinophil counts, who were uncontrolled despite receiving medium-to-high doses of ICS with or without an additional controller, and who had at least one asthma exacerbation in the prior year, were randomized to receive intravenously administered reslizumab (3.0 mg/kg) or placebo every four weeks for one year. Approximately 80% of patients in these trials were also taking an inhaled long-acting beta-agonist. The primary efficacy variable was the annual frequency of clinical asthma exacerbations. Lung function, quality of life, asthma control, and safety were also assessed.
Primary efficacy was met in both studies. Results were consistent and demonstrated that reslizumab reduced the annual frequency of clinical exacerbations by at least half (50% and 59% respectively), compared to placebo. Lung function also improved by week four and was maintained through one year in both studies. Furthermore, significant improvements were observed in the Asthma Quality of Life, Asthma Control Questionnaire and Asthma Symptom Utility Index scores. Common adverse events in the reslizumab treatment group were comparable to placebo and included worsening of asthma, nasopharyngitis, upper respiratory infections, sinusitis, influenza and headache. Two anaphylactic reactions were reported and resolved following medical treatment at the study site.
“We are immensely impressed by the continued positive results seen across the entire Phase III clinical trial program for reslizumab,” said Dr. Michael Hayden, President of Global R&D and Chief Scientific Officer at Teva Pharmaceutical Industries Ltd. “There is a tremendous need within the asthma patient population for targeted treatment options that may limit the number of annual exacerbations and aid patients in effectively controlling their condition. If approved, we look forward to bringing this important new therapy to market as soon as possible.”
The data published today in The Lancet Respiratory Medicine and presented at AAAAI are part of the comprehensive Phase III clinical trial program for reslizumab and further build upon Phase III trial data previously presented at the European Respiratory Society (ERS) International Congress in 2014. Regulatory submissions for reslizumab are planned for the first half of 2015.
Reslizumab is an investigational humanized monoclonal antibody (mAb) against interleukin-5 (IL-5). IL-5 has been shown to play a crucial role in the maturation, and survival of eosinophils, inflammatory white blood cells implicated in a number of allergic diseases, such as asthma. Elevated levels of blood eosinophils are a risk factor for future asthma exacerbations. Recent data from the Phase III clinical program demonstrated that reslizumab significantly reduced the annual rate of asthma exacerbations and improved lung function and asthma symptoms in patients with moderate to severe asthma with elevated blood eosinophils whose symptoms were inadequately controlled by medium to high doses of inhaled corticosteroids with or without an additional controller, compared with placebo.
About the Studies
In two duplicate, double-blind, Phase III studies, a total of 953 patients with similar baseline characteristics, and with moderate to severe asthma and elevated blood eosinophil levels were randomized to receive either intravenous reslizumab (3.0 mg/kg) (n=477) or placebo (n=476) every four weeks for one year. The primary endpoint was the annual frequency of clinical asthma exacerbations. Additional assessments included lung function, quality of life, asthma control and safety.
Results from these studies demonstrated that patients receiving reslizumab achieved reductions in clinical asthma exacerbations (study 1 RR 0.50 [95%CI 0.37, 0.67], study 2 RR 0.41 [95%CI 0.28, 0.59], both P<0.0001) versus placebo. lung function improved by the first assessment at week four, and was maintained for one year in both studies (change in fev>1 over 52 weeks was 0.126 L, P<0.0001 and 0.090 l, p="0.006)." significant improvements from baseline over 52 weeks were observed in asthma quality of life questionnaire scores (0.302, p="0.0004" and 0.234, p="0.0052)," asthma control questionnaire (-0.255, p="0.0002" and -0.242, p="0.0003)" and asthma symptom utility index (+0.061 [p><0.0001]; +0.036 [p="0.0011])." common adverse events in the reslizumab treatment group were similar to placebo; two anaphylactic reactions in the reslizumab arm were reported that resolved with treatment at the study site. overall, reslizumab significantly reduced the annual rate of clinical exacerbations and resulted in sustained improvement in secondary measures of asthma control compared with placebo.>0.0001];>0.0001>0.0001)>
Asthma is a chronic (long-term) disease usually characterized by airway inflammation and narrowing of the airways, which can vary over time. Asthma may cause recurring periods of wheezing (a whistling sound when you breathe), chest tightness, shortness of breath and coughing that often occurs at night or early in the morning. Without appropriate treatment, asthma symptoms may become more severe and result in an asthma attack, which can lead to hospitalization and even death.
Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a leading global pharmaceutical company that delivers high-quality, patient-centric healthcare solutions to millions of patients every day. Headquartered in Israel, Teva is the world’s largest generic medicines producer, leveraging its portfolio of more than 1,000 molecules to produce a wide range of generic products in nearly every therapeutic area. In specialty medicines, Teva has a world-leading position in innovative treatments for disorders of the central nervous system, including pain, as well as a strong portfolio of respiratory products. Teva integrates its generics and specialty capabilities in its global research and development division to create new ways of addressing unmet patient needs by combining drug development capabilities with devices, services and technologies. Teva's net revenues in 2014 amounted to $20.3 billion. For more information, visit www.tevapharm.com.
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