Elarekibep in Moderate-to-Severe Asthma: APATURA Trial Readout

Key Takeaways

• Week 4 pre-bronchodilator FEV1 favored elarekibep 3 mg over placebo in uncontrolled moderate-to-severe asthma.
• ACQ-6 scores were numerically better with elarekibep 1 mg and 3 mg than placebo, and part 1 treatment-emergent adverse events were mostly mild.
• The authors concluded that elarekibep was clinically well tolerated without identified short-term safety concerns, although development later stopped after non-human primate lung pathology findings.

In uncontrolled moderate-to-severe asthma, elarekibep 3 mg was associated with a 196 mL greater mean increase from baseline in pre-bronchodilator FEV1 than placebo at week 4. The APATURA phase 2a abstract describes a randomized, placebo-controlled, double-blinded, multicentre, two-part phase 2a study of inhaled elarekibep delivered twice daily by dry powder inhaler for 4 weeks. The 4-week readout also included short-term safety observations and pharmacokinetic findings across lung function, tolerability, and drug exposure.

Seventy-two patients were included overall, with 50 assigned to part 1 and 22 included in part 2. Part 1 enrolled patients with controlled moderate asthma and focused on safety and pharmacokinetics, while part 2 enrolled patients with uncontrolled moderate-to-severe asthma for efficacy versus placebo. Elarekibep was administered by dry powder inhaler twice daily for 4 weeks, with placebo serving as the comparator in both parts. The two-part design separated early safety and pharmacokinetic assessment from the placebo-controlled efficacy readout across distinct populations.

In part 2, the week 4 pre-bronchodilator FEV1 comparison versus placebo had a 95% confidence interval of 14.3 to 378 and a p value of 0.035. Asthma Control Questionnaire-6 scores at week 4 were numerically superior with elarekibep 1 mg and 3 mg than with placebo, with symptom differences reported at that timepoint only.

Approximately half of patients receiving elarekibep n = 20, 58.8%, or placebo n = 8, 50.0%, experienced at least one treatment-emergent adverse event in part 1. Most treatment-emergent adverse events were mild in intensity. Pharmacokinetic sampling showed steady absorption, with a median time to peak drug concentration of about 3 to 4 hours after dosing. These findings reflected the short-term safety and PK profile observed during the 4-week treatment period.

The investigators concluded that elarekibep was clinically well tolerated, with no identified short-term safety concerns during the trial. They also stated that development was terminated because of lung pathology findings in a 13-week non-human primate inhalation toxicology study, considered adverse and relevant to chronic clinical dosing. The authors also noted broader potential for inhaled biologic therapies in asthma. The trial findings were short term, while the development halt followed toxicology results outside the trial.