Elarekibep, an inhaled anti-IL-4 receptor alpha Anticalin, in moderate-to-severe asthma: a randomized, placebo-controlled phase 2a study (APATURA)

The pro-inflammatory cytokines interleukin (IL)-4 and IL-13 and their cognate receptor IL-4 receptor-alpha are key targets for asthma therapy. Elarekibep is an inhaled Anticalin protein developed to inhibit IL-4 receptor-alpha signalling in patients with moderate-to-severe asthma not controlled with standard-of-care therapies. APATURA was a phase 2a study (NCT04643158) investigating the efficacy and safety of elarekibep in patients with moderate-to-severe asthma. This was a randomized, placebo-controlled, double-blinded, multicentre, two-part study investigating elarekibep administered via dry powder inhaler twice daily for 4 weeks. Part 1 evaluated the safety and pharmacokinetics of elarekibep in patients with controlled moderate asthma, and part 2 evaluated the efficacy of elarekibep compared with placebo in those with uncontrolled moderate-to-severe asthma. In total, 72 patients were included (part 1: n = 50; part 2: n = 22) in the study. In part 1, approximately half of the patients receiving elarekibep (n = 20; 58.8%) or placebo (n = 8; 50.0%) experienced at least one treatment-emergent adverse event. Most of the treatment-emergent adverse events reported were of mild intensity. Elarekibep was steadily absorbed, with a median time to peak drug concentration of approximately 3–4 hours post-dose. In part 2, there was a mean increase from baseline in pre-bronchodilator forced expiratory volume in 1 second of 196 mL with elarekibep 3 mg compared with placebo (95% confidence interval: 14.3, 378; p = 0.035 vs placebo) at week 4. Improvements in Asthma Control Questionnaire-6 scores at week 4 were numerically superior with elarekibep 1 mg and 3 mg than with placebo. Elarekibep was clinically well tolerated with no identified short-term safety concerns. Development of elarekibep was terminated due to lung pathology findings in a 13-week non-human primate inhalation toxicology study, which were considered to be adverse and relevant for chronic clinical dosing. Nonetheless, the overall data demonstrate that there remains potential for the development of inhaled biologic therapies for patients with asthma that may offer advantages over systemically administered biologics. NCT04643158 (ClinicalTrials.gov). Registered 23 November 2020.