Study Highlights Impact of Rademikibart on Blood Eosinophil Counts in Asthma

A new analysis suggests that, unlike dupilumab, rademikibart does not cause eosinophil elevation in patients with asthma, highlighting a potential distinction in how the 2 biologics interact with interleukin (IL)-4Rα.1

These findings were presented in a poster session at the American Thoracic Society (ATS) International Conference in San Francisco. The poster for this new research was titled ‘Effect of Rademikibart on Blood Eosinophil Counts in Patients with Asthma: Is there an IL-4Rα Class Effect?’ and it was authored by such investigators as Raúl Collazo, PhD, vice president and Global Head of Medical Affairs for Connect Biopharma.

The subgroup of respiratory disorders, known as type 2 (T2) inflammatory airway diseases, are known to be marked by persistent inflammation that has been associated with T2 cytokines such as IL-4, IL-5, and IL-13. Such conditions are also known to commonly present with increased fractional exhaled nitric oxide (FeNO), elevated serum IgE levels, and high counts of eosinophils (Eos).

Collazo and coauthors highlighted that dupilumab treatment, designed to inhibit the IL-4 receptor alpha (IL-4Rα), has previously been linked to cases of hypereosinophilia. They added that this was especially noted among certain patients who started their course of therapy with eosinophil levels exceeding 500 cells/μL.

The next-generation IL-4Rα antagonist known as rademikibart has previously demonstrated in phase 2 findings several notable and sustained pulmonary function improvements, even as early as the first week and continuing through the 24-week mark. Collazo et al sought to evaluate whether eosinophilia is a class effect common to IL-4R blockade, looking at safety data from that phase 2 analysis and at those with uncontrolled moderate-to-severe asthma.

There were 322 individuals recruited for this phase 2b clinical study, which involved a global, randomized, placebo-controlled design. At 79 sites, the investigative team randomized participants in a 1:1:1 ratio to receive either rademikibart 150 mg on a basis of every 2 weeks (Q2W; n=106), rademikibart 300 mg Q2W involving a 600 mg loading dose (n=108), or a placebo (n=108).

The incidence of eosinophilia (defined as Eos >1500 cells/μL) as well as hypereosinophilia (Eos >3000 cells/μL) was evaluated by Collazo and colleagues, across the full study population and in a subgroup with elevated baseline eosinophils (>500 cells/μL). These findings pertain to the higher 300 mg Q2W dosage group.

At the 24-week mark, those treated with rademikibart saw a greater eosinophil count reduction from the point of baseline versus those in the placebo group.1 The percent changes were as follows:

• Week 1: -4.6% for those on rademikibart versus -0.3% for placebo
• Week 4: -11.9% versus -1.7%
• Week 24: -38.5% versus -10.7%

In the investigators’ evaluation of subjects with baseline eosinophil levels above 500 cells/μL, it was noted that 10% of those on rademikibart were shown to have a peak eosinophil count exceeding 1500 cells/μL at any point during the course of the analysis. This was compared to 18.8% observed in the placebo cohort.

In 1 notable finding, Collazo and coauthors highlighted that no participants included in the rademikibart arm of the study (0%) attained the threshold for hypereosinophilia (>3000 cells/μL). Overall, they also concluded that rademikibart’s safety profile was favorable and aligned with prior data.

While prior research on dupilumab has indicated that the drug was associated with eosinophilia in 42% of individuals using the drug and hypereosinophilia in 13%, the present analysis suggests that there is consistency in the eosinophil changes in the placebo arms across different studies.

This would indicate that the differences observed by the investigative team in treatment arms are likely attributable to the specific drug being evaluated, thus supporting the notion that rademikibart does not share the same eosinophil-related effects as dupilumab.

For more data at ATS 2025, view our latest conference coverage.

References

1. Collazo R, Wechsler M, Quart B. (Poster Board # P1515) Effect of Rademikibart on Blood Eosinophil Counts in Patients With Asthma: Is There an IL-4Rα Class Effect? Abstract presented at the American Thoracic Society (ATS) International Conference 2025 in San Francisco, CA, from May 18 - May 21, 2025.