Rademikibart Yields Rapid Improvements in Moderate to Severe Uncontrolled Asthma

Rademikibart quickly improved clinical outcomes in patients with moderate-to-severe uncontrolled asthma, including forced expiratory volume in 1 second (FEV1) and clinically important reductions in annual exacerbation rates, according to new data published in American Journal of Respiratory and Critical Care Medicine (AJRCCM).1

“It is notable that rademikibart, particularly in patients with true eosinophilic driven asthma, was associated with numerically larger placebo-adjusted improvements in FEV1 than those previously reported for other biologics,” Michael E. Wechsler, MD, MMSc, Professor of Medicine and Director, NJH Cohen Family Asthma Institute at National Jewish Health in Denver, Colorado, said in a statement.2 “These numerically larger improvements in efficacy were obtained with no incidents of hypereosinophilia, suggesting that increases in eosinophil levels previously observed are not an IL-4Rα class effect.”

The new data are from a global, phase 2b CBP-201-WW002 trial (NCT04773678) evaluating the safety and efficacy of the biologic in 322 adult participants with moderate-to-severe, persistent, uncontrolled asthma. Participants, across 78 study centers in the United States China, Poland, South Korea, and Hungary were randomized 1:1:1 to rademikibart 150 mg or 300 mg every 2 weeks, following a 600 mg loading dose, or placebo, administered subcutaneously, for 24 weeks. Overall, 88% of participants completed treatment.

The investigators found that prebronchodilator FEV1 at Week 12 improved in the rademikibart 150 mg group (least squares mean [LSM] change, +140 mL above placebo [95% CI, 44-236]; P = .005) and 300 mg group (LSM, +189 mL above placebo [95% CI, 92-286]; P <.001) compared to placebo. These improvements improvements occurred rapidly during Week 1 and were sustained through Week 24. Notably, participants with high baseline blood eosinophils (≥300 eosinophils/mL; n = 40) had the greatest improvements, with a +420 mL increase above placebo (95% CI, 239-600) in the 300 mg group. This group had a week 1 FEV1 improvement of +312 mL. All patients with at least 150 eosinophils/µL at baseline receiving rademikibart 150 or 300 mL had significant increases in FEV1.1

Furthermore, participants receiving rademikibart had 24 acute exacerbations in 214 patients compared with 26 events in 108 patients receiving placebo. Through Week 24, 7.5% of participants in the 150 mg group and 9.3% in the 300 mg group had at least 1 exacerbation, compared with 16.7% of the placebo group.1

Asthma Control Questionnaire (ACQ-5) scores also reflected rapid statistically significant improvements in asthma control in both rademikibart groups compared with placebo at week 2, continuing through week 24.

In terms of safety, rademikibart was generally well-tolerated with mostly mild-to-moderate treatment-emergent adverse events (TEAEs) and no serious TEAEs related to treatment. The most common TEAEs (10-12% of patients) were cough, COVID-19, and dyspnea.

There were no eosinophilia-related TEAEs, and no patients with baseline eosinophils over 500 cells/µL exhibited a peak eosinophil level of >3000 cells/µL. Connect favorably compared rademikibart’s safety profile with that of dupilumab in clinical trials, in which almost 13% of a similar population reaching a peak eosinophil level of >3000 cells/µL.

“Publication in AJRCCM of the results from the Phase 2 study of rademikibart in patients with chronic moderate-to-severe asthma and Type 2 inflammation underscores the potentially significant impact of rademikibart for these patient populations. Given the substantial increases in FEV1, clinically meaningful decreases in exacerbations, and the favorable safety profile observed in the Phase 2 trial, rademikibart has the potential to benefit patients with chronic asthma and patients with other respiratory diseases with Type 2 inflammation such as COPD,” Barry Quart, PharmD, CEO and Board Director of Connect Biopharma, added.2 “Based on these data and post hoc analyses soon to be presented at the upcoming American Thoracic Society meeting, we believe there is a significant opportunity to study rademikibart during the four weeks following an acute exacerbation of asthma or COPD, a vulnerable period when approximately half of patients who receive current standard of care will experience another exacerbation and where no biologic therapies have been approved or systematically studied. We believe the unique clinical profile of rademikibart may provide significant benefit during this critical period and look forward to sharing the outcomes from our upcoming Phase 2 trials in acute asthma and COPD.”

Connect also shared that it had received agreement from the FDA in an end-of-Phase 2 meeting with the Division of Pulmonology, Allergy, and Critical Care, in the Office of Immunology and Inflammation, to advance rademikibart into Phase 3 trials for the maintenance treatment of asthma based off the phase 2b data.2

REFERENCES

1. Kerwin E, Yang T, Su N, et al. Rademikibart Treatment for Moderate-to-Severe, Uncontrolled Asthma: A Phase 2B Randomized Trial. Am. J. Respir. Crit. Care Med. 2025; 0(ja). doi: 10.1164/rccm.202409-1708OC

2. Connect Biopharma Announces Publication of Positive Data from Global Phase 2 Trial of Rademikibart in Patients with Moderate-to-Severe Uncontrolled Asthma. News release. Connect Biopharma. March 31, 2025. https://www.globenewswire.com/news-release/2025/03/31/3052769/0/en/Connect-Biopharma-Announces-Publication-of-Positive-Data-from-Global-Phase-2-Trial-of-Rademikibart-in-Patients-with-Moderate-to-Severe-Uncontrolled-Asthma.html