Phase 2 Data on Rilzabrutinib as Rescue Medication for Asthma, with William Busse, MD

In a new interview with the HCPLive editorial team, William W. Busse, MD, of the University of Wisconsin School of Medicine and Public Health, touched on the results of a phase 2 study assessing rilzabrutinib’s impact on reducing loss of asthma control events in individuals with uncontrolled moderate-to-severe asthma.1

The poster, presented at the American Thoracic Society (ATS) 2025 International Conference in San Francisco, was titled ‘Reduction in the Use of Rescue Medication for Asthma Symptom Relief With Rilzabrutinib: Results from a Phase 2 Study.’1 Busse was asked about the study design, its findings, and the significance of these results for health care providers.

HCPLive: Can you walk us through the design of the phase 2 study?

Busse: The 12-week, double-blind, placebo-controlled, 2-staggered-cohort study evaluated rilzabrutinib in poorly controlled adult patients with moderate-to-severe asthma. The primary endpoint was the proportion of participants with a loss of asthma control (LOAC) event, as defined and assessed by the use of >6 additional reliever puffs of a short-acting β2 adrenergic agonist (SABA) rescue inhaler in a 24-hour period.

The study enrolled 196 patients with poorly controlled disease using inhaled corticosteroids (ICS) and a long-acting β2 adrenergic agonist (LABA) therapy. Patients were randomized 1:1 first to rilzabrutinib 800mg (400 mg twice daily; n=32) or placebo (n=32) and then to rilzabrutinib 1200mg (400mg three times daily; n=64) or placebo (n=68).

HCPLive: What were the key findings regarding rilzabrutinib’s impact on the use of rescue medication?

Busse: In this study, treatment with oral rilzabrutinib (800mg or 1200mg) over 12 weeks was associated with a reduction in LOAC events in uncontrolled patients with moderate-to-severe asthma. At Week 12, the proportion of participants requiring rescue medication was 6.3% for rilzabrutinib 800mg and 0% for rilzabrutinib 1200mg, compared to 12.5% and 10.3%, respectively, for the placebo groups.

An overall reduction in patients requiring rescue medication with rilzabrutinib was also observed across different thresholds over 12 weeks: 9.4% (800mg) and 6.3% (1200mg) of rilzabrutinib-treated patients required >3 additional reliever puffs, compared to 21.9% and 23.5% of placebo-treated patients, respectively; 6.3% (800mg) and 4.7% (1200mg) of rilzabrutinib-treated patients required >4 additional reliever puffs, compared to 18.8% and 17.6% of placebo-treated patients, respectively; 6.3% (800mg) and 1.6% (1200mg) of rilzabrutinib-treated patients required >5 additional reliever puffs, compared to 12.5% and 14.7% of placebo-treated patients, respectively.

These data add to the growing body of clinical evidence supporting rilzabrutinib’s potential as an oral therapy to manage the burden of asthma in uncontrolled moderate-to-severe patients.

HCPLive: Were there any surprising secondary outcomes or trends observed in symptom control or lung function? Did rilzabrutinib appear to influence other indicators of disease severity or inflammation?

Busse: The results were encouraging as this is a new regulatory pathway in the inflammatory response in asthma. Although the specific effects on inflammation were not established, a reduction in LOAC points to anti-inflammatory actions.

HCPLive: How does rilzabrutinib’s mechanism of action as a BTK inhibitor potentially address the underlying drivers of asthma exacerbations? How might this differ from currently approved biologics?

Busse: BTK, expressed in B cells, macrophages, and other immune cells, plays a critical role in inflammatory pathways and multiple immune-mediated disease processes, including those implicated in asthma. By inhibiting BTK, rilzabrutinib has potential to downregulate the underlying immune mechanisms driving asthma-related inflammation, which could help reduce symptoms and LOAC events, and even predict a future reduction in exacerbations for asthma patients.

That said, it’s important to note that multiple mechanisms can cause the inflammation underlying immune-inflammatory conditions, including asthma. Currently approved biologics target some of these pathways, including the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways, but there remains a need for new modes of action, like BTK inhibition, to help offer patients and physicians a diverse toolkit of options for treating these diseases.

HCPLive: What safety or tolerability signals emerged in this study, if any? Were there any specific patient subgroups that responded particularly well—or poorly—to rilzabrutinib?

Busse: The safety profile of rilzabrutinib was consistent with previous studies, with no new safety signals observed. The lack of adverse events is reassuring given the actions of rilzabrutinib on tyrosine kinases.

HCPLive: What are the next steps for rilzabrutinib in asthma? Do you anticipate a phase 3 trial, and what would you hope to further investigate?

Attributed to Sanofi spokesperson, Leda Mannent, Global Project Head, Immunology & Inflammation at Sanofi: Sanofi is evaluating next steps for our rilzabrutinib clinical program in asthma based on ongoing discussions with global regulators. However, it would be premature to discuss timing or plans for additional studies while those conversations are ongoing. Beyond asthma, rilzabrutinib is being studied in a number of chronic inflammatory diseases, including immune thrombocytopenia (ITP; phase 3), chronic spontaneous urticaria (CSU; phase 2), prurigo nodularis (PN; phase 3), IgG4-related disease (phase 2), and warm autoimmune hemolytic anemia (wAIHA; phase 2).

For more information on data released at ATS 2025, view HCPLive’s latest conference coverage.

Busse has previously reported receiving grant funding from the National Institute of Allergy and Infectious Diseases and the National Heart, Lung, and Blood Institute and receiving personal fees for consulting from AstraZeneca, Genentech, GlaxoSmithKline, Novartis, Sanofi, and Regeneron.

References

1. Busse WW, Maspero JF, Martincova R, et al. Reduction in the Use of Rescue Medication for Asthma Symptom Relief With Rilzabrutinib: Results From a Phase 2 Study. Abstract presented at the American Thoracic Society (ATS) International Conference 2025 in San Francisco, CA, from May 18 - May 21, 2025.