Connect Biopharma has announced the publication of positive results from its global Phase 2 trial of rademikibart in patients with moderate-to-severe uncontrolled asthma. The findings, published in the American Journal of Respiratory and Critical Care Medicine (AJRCCM), demonstrate the potential of this novel anti-interleukin-4-receptor alpha (IL-4Rα) antibody as a breakthrough treatment for asthma patients with Type 2 inflammation.
The Phase 2 trial (CBP-201-WW002) enrolled 322 adult patients with moderate-to-severe, persistent, uncontrolled asthma, with two-thirds of participants treated in the United States. Patients were randomized 1:1:1 to receive either rademikibart 150 mg, 300 mg (both administered every two weeks following a 600 mg loading dose), or placebo, delivered subcutaneously over 24 weeks.
Exceptional Lung Function Improvements
Results revealed clinically meaningful and statistically significant improvements in lung function, with benefits observed as early as one week after treatment initiation and sustained throughout the 24-week study period. The primary endpoint of prebronchodilator forced expiratory volume in one second (FEV1) showed remarkable improvements:
- In patients with ≥300 eosinophils/μL at baseline receiving rademikibart 300 mg, the mean difference from placebo in FEV1 was +420 mL at Week 24
- The Week 1 FEV1 improvement in these patients was already substantial at +312 mL
- Significant increases in FEV1 were observed in both rademikibart dose groups across all high eosinophil count subgroups (≥150 cells/μL at baseline)
"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," said Michael E. Wechsler, MD, MMSc, Professor of Medicine and Director, NJH Cohen Family Asthma Institute at National Jewish Health in Denver, Colorado.
Reduced Exacerbations and Improved Asthma Control
Beyond lung function improvements, the trial demonstrated additional clinical benefits:
- Patients receiving rademikibart experienced substantially fewer acute exacerbations (24 events in 214 patients) compared to those on placebo (26 events in 108 patients)
- Asthma control, measured by the five-question Asthma Control Questionnaire (ACQ-5), improved rapidly with statistical significance for both rademikibart doses compared to placebo at Week 2
- These improvements continued through Week 24 in the overall population
Favorable Safety Profile
Rademikibart was generally well-tolerated throughout the study:
- Most treatment-emergent adverse events (TEAEs) were mild or moderate in intensity
- No serious TEAEs were related to treatment with rademikibart
- Notably, no eosinophilia-related TEAEs were reported for rademikibart
- No patients with baseline eosinophils over 500 cells/μL exhibited peak eosinophil levels >3000 cells/μL, comparing favorably to the nearly 13% reported in clinical trials of dupilumab in similar patient populations
This safety profile suggests that increases in eosinophil levels previously observed with other IL-4Rα inhibitors may not be a class effect, potentially differentiating rademikibart from existing therapies.
Path Forward to Phase 3
Based on these promising results, Connect Biopharma has received agreement from the U.S. Food and Drug Administration to advance rademikibart into Phase 3 trials for the maintenance treatment of asthma.
"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," said Barry Quart, Pharm.D., CEO and Board Director of Connect Biopharma.
Dr. Quart added, "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."
Addressing Unmet Needs in Respiratory Care
Connect Biopharma is also exploring rademikibart's potential in acute settings. The company plans to study the drug during the four weeks following acute exacerbations of asthma or COPD—a vulnerable period when approximately half of patients receiving current standard of care experience another exacerbation.
This represents a significant unmet need, as no biologic therapies have been approved or systematically studied for this critical period. With approximately 1 million asthma patients and 1.3 million COPD patients in the U.S. experiencing acute exacerbations annually, rademikibart could address a substantial treatment gap.
The rapid onset of action observed in the Phase 2 trial—with improvements seen within one week and in most cases within 24 hours via home spirometry—suggests rademikibart may be particularly well-suited for acute intervention.
About Rademikibart and Connect Biopharma
Rademikibart is a next-generation anti-IL-4Rα antibody being developed by Connect Biopharma, a clinical-stage biopharmaceutical company headquartered in San Diego, California. The company is focused on transforming both acute and chronic care of asthma and COPD.
The company believes rademikibart's unique clinical profile, including rapid onset of action and favorable safety characteristics, positions it as a potentially best-in-class therapy that could significantly improve outcomes for patients with moderate-to-severe asthma and other respiratory conditions characterized by Type 2 inflammation.
Connect Biopharma plans to present additional post hoc analyses from the Phase 2 trial at the upcoming American Thoracic Society meeting and is preparing to launch Phase 2 trials in acute asthma and COPD.
