Date: 2014-09-27
Type of information: Results
phase: 3
Announcement: results
Company: Teva Pharmaceutical Industries (Israel)
Product: reslizumab
Action
mechanism: 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, growth and chemotaxis (movement) of eosinophils, inflammatory white blood cells implicated in a number of allergic diseases.
Disease: asthma
Therapeutic area: Allergic diseases - Inflammatory diseases - Respiratory diseases
Country: USA, Argentina, Australia, Brazil, Denmark, Canada, Chile, Colombia, Czech Republic , France, Germany, Greece, Israel, Korea, Mexico, New Zealand, Poland, Romania, Russia, South Africa, Sweden,Taiwan ,
Trial
details: Study NCT01287039 was a Phase III, 12-month, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, and immunogenicity of treatment with reslizumab in 489 patients with eosinophilic asthma. Its primary objective was to demonstrate the efficacy of reslizumab, at a dose of 3 mg/kg administered IV every 4 weeks, as assessed by the reduction in frequency of clinical asthma exacerbations (CAEs). Professor Mario Castro , MD, Washington University School of Medicine , Division of Pulmonary and Critical Care Medicine, was the principal investigator. Study was conducted in 128 study centers. Study NCT01285323 was a Phase III, 12-month, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of reslizumab treatment (3 mg/kg administered IV every 4 weeks) in the reduction of clinical asthma exacerbations in 464 patients (12-75 years of age) with eosinophilic asthma whose symptoms are inadequately controlled with inhaled corticosteroids. Principal investigator - Dr. Stephanie Korn , Head of Clinical Research Pulmonology, Asthma and COPD clinic, Mainz University Hospital in Germany . Study was conducted in 104 study centers. Study NCT01270464 was a 16-week, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of reslizumab (0.3 or 3.0 mg/kg) as treatment for patients (12-75 years of age, n=311) with eosinophilic asthma. The primary objective was is to determine whether reslizumab administered once every 4 weeks for a total of 4 doses, is more effective than placebo in improving lung function in patients with eosinophilic asthma. Study NCT01508936 was a 16-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of reslizumab (3.0 mg/kg IV injection every four weeks) treatment in patients (18-65 years of age, n= 492) with moderate to severe asthma. The primary objective of the study was to assess reslizumab effect on FEV1 in relation to baseline blood eosinophils in subjects with moderate to severe asthma.
Latest
news: * On September 27, 2015, Teva Pharmaceutical Industries presented results from a post hoc analysis of two pivotal Phase III clinical trials showing that treatment with reslizumab reduced clinical asthma exacerbations (CAEs) by 75 percent versus placebo in a subgroup of patients with late onset asthma (diagnosed at 40 years of age and older) with elevated blood eosinophils, who were inadequately controlled on inhaled corticosteroids (ICS). These results were presented as a late-breaking abstract at the 2015 ERS International Congress in Amsterdam . In order to determine the influence that age of asthma onset has as it relates to the efficacy of reslizumab, results were pooled from two Phase III clinical trials that investigated reslizumab IV 3 mg/kg in patients who were inadequately controlled on an ICS-based regimen, who had at least one asthma exacerbation within the previous 12 months, and a blood eosinophil count of =400/µL. These post-hoc analysis results indicate that, in the subgroup with late onset asthma, reslizumab showed a 75 percent reduction in asthma exacerbations and improvement in lung function as measured by forced expiratory volume in one second (FEV1). In the overall pooled patient population, asthma exacerbations were reduced by 54 percent; in the subgroup of subjects diagnosed with asthma at <40 years of age, exacerbations were reduced by 42 percent. Data for this post-hoc analysis were pooled from two identical Phase III clinical trials (which were part of the BREATH clinical program) that comprised four placebo-controlled studies whose population of 1,700 adult and adolescent asthma patients (aged 12-75 years) had elevated blood eosinophils and symptoms that were inadequately controlled with ICS-based therapies. Common adverse events (occurring in >5 percent of patients overall) in the reslizumab treatment group were comparable to placebo and included asthma, nasopharyngitis, upper respiratory infections, sinusitis, influenza and headache. Two patients treated with reslizumab experienced anaphylactic reactions. In both cases, patients responded to standard treatment administered at the study centre. Patients were then withdrawn from participation in the study. * On September 8, 2014 , Teva Pharmaceutical Industries announced positive new data from Phase III studies of the company’s anti-IL5 monoclonal antibody, reslizumab, in patients with uncontrolled moderate to severe asthma with elevated eosinophils, treated with standard of care therapies. The data demonstrated that reslizumab treatment resulted in significant improvement in lung function and asthma control measures and showed a safety profile comparable to placebo. Reslizumab treatment (3.0 mg/kg and 0.3 mg/kg IV injection every four weeks) resulted in significant improvements in lung function versus placebo when administered to patients, with moderate to severe asthma with elevated eosinophils. Improvement was measured by overall change in Forced Expiratory Volume in 1 second (FEV1), a standard measure of the degree of airway obstruction in asthma. Improvements were noted as early as four weeks after initial dose administration and were maintained at the end of the 16 week treatment period. Furthermore, reslizumab produced significant improvements in patient reported asthma control, assessed by using the Asthma Control Questionnaire (ACQ), which includes questions on symptoms, activity limitation, and the use of non-steroidal rescue medication. Improvements in FEV1 and ACQ for the 0.3 mg/kg dose were numerically smaller than for the 3 mg/kgdose.The majority of reported adverse events (AEs) were mild to moderate and comparable across the treatment groups. The most common AEs in any treatment group were asthma, headache, nasopharyngitis, and upper respiratory tract infection. The results announced provide a strong foundation for investigation of additional indications, such as COPD with elevated eosinophils. The ongoing development of a subcutaneous formulation will further strengthen the franchise and is expected to be submitted for approval in the second half of 2017.
Results from a second study, utilizing only the 3 mg/kg dose of reslizumab, in an asthma population that was not selected for elevated blood eosinophils, demonstrated minimal improvements in asthma control, and provides support for the eosinophil threshold of ≥400/µL set for the reslizumab phase III program.
Teva-Sponsored Data Highlights Include:
A randomized phase III study of the efficacy and safety of reslizumab in subjects with asthma with elevated eosinophils (Poster Presentation on Sunday, Sept 7, 2014. 8:30 – 10:30am. Session 57) Leif Bjermer, Catherine Lemiere, Jorge Maspero, Monika Ciesielska, Christopher O'Brien, James Zangrilli.
A randomized phase III study of reslizumab efficacy in relation to blood eosinophil levels in patients with moderate to severe asthma (Oral Presentation: Wednesday, Sept 10, 2014. 10:15am. Session 488) Jonathan Corren, Steven Weinstein, Lindsay Janka, Christopher O'Brien, James Zangrilli
* On September 2, 2014, Teva Pharmaceutical Industries announced that reslizumab, an investigational anti-IL-5 monoclonal antibody, demonstrated clear levels of efficacy in achieving the primary endpoint of reduction in the frequency of clinical asthma exacerbations (CAE) compared to placebo in two pivotal Phase III studies in patients with inadequately controlled moderate to severe asthma with elevated levels of blood eosinophils. In both trials, reslizumab treatment showed both clinically relevant and statistically significant reductions in the frequency of CAE compared to placebo (50% and 60% respectively, p This initial set of results shows the adverse event profile of reslizumab was comparable to placebo in both trials. The incidence of common AEs (> 5%) was consistent with those seen in a moderate to severe asthma population, the most frequent being upper respiratory tract infections, asthma and headache. Further analyses of additional efficacy and safety data are ongoing.
The two pivotal Phase III studies involved 953 patients across 232 medical centers worldwide including the US, EU and the Far East. These studies are part of the Phase III BREATH program that evaluated the safety and efficacy of reslizumab treatment in four separate Phase III trials involving more than 1700 adolescent and adult asthma patients with elevated eosinophils, whose symptoms were inadequately controlled with inhaled corticosteroids with or without another controller medication.Detailed analyses of the data are ongoing and full results will be submitted for presentation to a future scientific meeting and for publication in a peer reviewed journal. Teva Pharmaceutical Industries plans to submit applications for approval in the US, Europe and other regions as soon as possible.
