Two phase 3 studies evaluating a fixed 110-mg subcutaneous dose of reslizumab (Cinqair, Teva Pharmaceutical Industries Ltd.) failed to meet their primary endpoints: reducing exacerbations in patients with uncontrolled asthma in one trial, and reducing oral corticosteroid doses in asthma patients dependent on those drugs in the other trial.
Both studies tested the safety and efficacy of the 110-mg dose every four weeks, Teva said.
Study NCT02452190 was a 52-week, registration, double-blind, placebo-controlled study designed to evaluate reslizumab given in a pre-filled syringe in 468 patients with uncontrolled asthma and elevated blood eosinophils (more than 300/mcL). It failed to meet its primary objective of demonstrating the efficacy of reslizumab as assessed by the reduction in frequency of clinical asthma exacerbations (CAEs).
Study NCT02501629 was a claim-support, 24-week, double-blind, placebo-controlled, parallel-group study to evaluate reslizumab in 177 patients with oral corticosteroid (OCS)–dependent asthma and elevated blood eosinophils. Its primary objective was to demonstrate the efficacy of the fixed dose of reslizumab as assessed by reduction in daily OCS dose compared with baseline, an endpoint it failed to meet.
“We are disappointed that these trials of the reslizumab formulation administered subcutaneously at a fixed dose of 110 mg did not meet their primary endpoints. However, these results reinforce the role of eosinophils in severe asthma disease biology and the importance of defining the right blood eosinophil cutoff point for patient selection. We continue to see the positive impact of the intravenous formulation as a clinically effective 3 mg/kg weight-based dosing option in patients with asthma and elevated blood eosinophils who are inadequately controlled on standard-of-care therapy,” said Tushar Shah, MD, Senior Vice President, Specialty Clinical Development and Medical Affairs at Teva.
In the registration study, a prespecified a priori-powered subgroup analysis of 80% of the total randomized severe asthma patient population with baseline blood eosinophil count of at least 400/mcL showed significant reduction in CAE risk (P < 0.025). This patient population is similar to those studied in the phase 3 clinical trials for Cinqair injection, the currently approved intravenous formulation, which also used a blood eosinophil count of 400/mcL or greater.
Teva will review the full data to determine next steps.
No new safety concerns to the known safety profile of reslizumab were identified in review of the data from these studies and no cases of anaphylaxis related to reslizumab were reported.
Reslizumab injection is an interleukin-5 antagonist monoclonal antibody (IgG4 kappa) indicated for add-on maintenance treatment of patients 18 years of age and older who have severe asthma with an eosinophilic phenotype.
Source: Teva; January 22, 2018.