Q&A: Rademikibart may be ‘transformational therapy’ for moderate to severe asthma

Key takeaways:

• Rademikibart led to better lung function and asthma control in adults with moderate to severe persistent asthma vs. placebo.
• Researchers said this drug “may be better than dupilumab.”

Topline results from a phase 2b trial revealed that rademikibart led to improvements in lung function and asthma control in adults with moderate to severe persistent asthma compared with placebo.

In this global, multicenter, randomized, double-blind, placebo-controlled study, rademikibart (CBP-201, Connect BioPharma) was given to patients every 2 weeks for 24 weeks as either a 150 mg dose (n = 106) or a 300 mg dose (n = 108). The placebo group included 108 patients.

By week 12, patients receiving rademikibart had greater improvements in pre-bronchodilator FEV₁ compared with patients receiving placebo (difference in least square means: 150 mg dose, 140 mL; P = .005; 300 mg dose, 189 mL; P < .001).

Researchers further found significant absolute changes in Asthma Control Questionnaire (ACQ) scores between baseline and week 24 in both rademikibart groups (150 mg, –0.44; P < .001; 300 mg, –0.33; P < .01) after adjusting for placebo.

To learn more about this trial, the drug and future research, Healio spoke with Edward Kerwin, MD, medical director of Clinical Research Institute in the Allergy and Asthma Center of Southern Oregon.

Healio: Were any of the study findings unexpected or surprising?

Kerwin: Yes, a phase 2 study with 100 patients per treatment arm normally might show an 80 mL to 100 mL improvement in FEV₁ at week 12 with a P value less than .05 or perhaps equal to .01, but in this rademikibart asthma study, the “effect sizes” of rademikibart were much larger. FEV₁ improved by 140 mL to 189 mL over placebo, and the P values were less than .001. This is a remarkable effect size and remarkable P value for a fairly small phase 2 trial.

Additionally, the secondary endpoints that were measured daily or weekly also showed highly statistically significant benefits in favor of rademikibart (with P values < .001 or in some cases < .01). This is quite unusual for a small phase 2 trial. Rademikibart helped patients to feel better (to feel successful asthma control, as measured by the ACQ-6 scores) in the very first days and weeks after they received their initial dose injection (compared with placebo patients). The medication worked even in the first few days and weeks and over the course of the study, which is quite unusual.

For instance, the CAPTAIN study, published in 2020 in The Lancet Respiratory Medicine looked at fluticasone furoate, umeclidinium and vilanterol (Trelegy, GSK) vs. fluticasone and vilanterol (Breo, GSK) for patients exacerbation-prone asthma. Even with about 400 patients in each treatment group, the CAPTAIN study did not show significant ACQ improvements for treatments vs. control inhaled corticosteroid/long-acting beta-agonist (let alone show ACQ improving by P < .001).

The high success rate for primary and secondary endpoints in the phase 2b asthma study means that future rademikibart studies are very likely to be successful. The very high level of statistical significance achieved also means that fewer patients may be needed for a pivotal phase 3 trial to confirm rademikibart’s effectiveness for asthma airflow (FEV₁) and for its ability to reduce asthma exacerbations.

These are great, highly impressive data in favor of rademikibart’s effectiveness in helping patients with asthma.

Healio: Could you describe rademikibart’s potential for a highly competitive efficacy and safety profile?

Kerwin: Asthma biologic medicines succeed based on several factors that make the drug the most high-quality successful treatment available. These factors include:

• potency to cause a benefit to disease;
• ability to help a high percentage of treated patients (near 100%);
• ability to help fully or completely improve the targeted disease state (such as asthma);
• ability to help “the whole patient,” for instance helping multiple atopic diseases, such as asthma (ie, lung allergies), and at the same time helping rhinitis and sinusitis (ie, nose allergies) and atopic dermatitis (ie, skin allergies), and potentially helping gastrointestinal or food allergies, such as eosinophilic esophagitis;
• convenient dosing;
• safety, where all treatment benefits accrue with minimal or acceptable safety risks;
• reasonable cost for patients; and
• ability of the medicine to be used globally across a variety of countries and health care settings.

Rademikibart may be better than dupilumab (Dupixent; Regeneron, Sanofi) because rademikibart has stronger potency. It may be able to be dosed every 4 weeks or monthly and be released at a favorable cost advantage (especially if dosing is every 4 weeks long term). Further, it may potentially become more globally available (eg, in China and Asia over time).

Rademikibart looks like a potential “superstar” biologic for atopic T2-high diseases. It appears to be approximately at least as good as the current market leader, dupilumab, and potentially better in some of the indices identified above.

Healio: Would you briefly characterize what the impact of the findings are for the everyday clinician?

Kerwin: If approved, and if phase 3 data confirm current phase 2/phase 3 benefits seen, then rademikibart based on initial findings for asthma and atopic dermatitis could be a transformational therapy. It could be dosed monthly for patients with uncontrolled atopic diseases, and lead to a high level of disease control and stabilization with minimal side effect risk. Patients may tolerate this treatment very well as a monthly, at-home injected therapy.

Healio: How will future studies be different?

Kerwin: Because of the very strong “effect size” on FEV₁ and ACQ-6 etc., and the very high P values (eg, P < .001) seen across several primary and secondary endpoints in the phase 2 asthma trial, future phase 3 studies can be smaller, with fewer patients needed in each treatment arm to effectively power the study. Smaller studies can be quicker to accomplish and less expensive for sponsors such as Connect Biopharma, so a phase 3 program might be able to be launched fairly soon (possibly in late 2024). Further, future phase 3 studies are more likely to be successful based on the very strong success and efficacy seen in phase 2 studies.

References:

• Connect Biopharma announces positive rademikibart global phase 2b topline results in adult patients with moderate to severe persistent asthma. https://investors.connectbiopharm.com/news-releases/news-release-details/connect-biopharma-announces-positive-rademikibart-global-phase. Published Dec. 12, 2023. Accessed Dec. 12, 2023.
• Lee LA, et al. Lancet Respir Med. 2021;doi: 10.1016/S2213-2600(20)30389-1.