Phase 2 Study Demonstrates Oral Rilzabrutinib Reduces Loss of Control Events in Patients With Asthma


According to the investigators, these findings support the investigation of rilzabrutinib in patients with asthma in a phase 3 trial program.

Positive results from a phase 2 trial (NCT05104892) demonstrate that treatment with oral rilzabrutinib at both a high and low dose led to a numerical reduction in loss of asthma control (LOAC) events. The results were presented at the 2024 American Thoracic Society International Conference in San Diego, which was held May 17 to May 22.1

X-ray of lungs with asthma -- Image credit: magicmine |

Image credit: magicmine |

Rilzabrutinib is an oral, reversible, covalent Bruton tyrosine kinase (BTK) inhibitor that could potentially be a first- and/or best-in-class treatment for multiple immune mediated diseases. BTK, which is expressed in B cells and mast cells, plays a significant role in multiple immune-mediated disease processes, and the treatment can selectively inhibit the BTK target while potentially reducing the risk of off-target side effects.1

Currently, rilzabrutinib is being studied across multiple immune-mediated diseases, including asthma, chronic spontaneous urticaria, prurigo nodularis, IgG4-related disease, and warm autoimmune hemolytic anemia. Additionally, in the recent randomized, multicenter phase 3 LUNA 3 trial (NCT04562766), rilzabrutinib met the primary end point and demonstrated a durable platelet response in adult patients with persistent or chronic immune thrombocytopenia (ITP).1,2

About the Trial

Trial Name: Proof of Concept Study of Rilzabrutinib in Adult Participants With Moderate-to-severe Asthma ID: NCT05104892

Sponsor: Sanofi

Completion Date: February 28, 2024

“Many of my patients with asthma who are treated with standard of care inhaled therapies, even those with infrequent asthma attacks, still suffer from asthma symptoms and their activities are limited because of it. These patients may not qualify for a biologic medicine today but could benefit from an oral therapy that intervenes earlier in the disease,” said Tanya M. Laidlaw, MD, director of Translational Research in Allergy, Brigham and Women’s Hospital, Boston, Massachusetts, in a press release.1

The phase 2 trial is a randomized, double-blind, placebo-controlled, parallel-group, 12-week proof-of-concept study to assess the safety, efficacy and tolerability of rilzabrutinib in patients with moderate to severe asthma. These patients were not considered well-controlled on inhaled corticosteroids (ICS) plus long acting β2 adrenergic agonist (LABA) therapy. Patients were randomly assigned to receive treatment with daily doses of rilzabrutinib (800 mg or 1200 mg) or placebo, which was added to a background therapy of ICS/LABA that was withdrawn during the 12-week treatment period. The study’s primary end point was reduction in LOAC events, which was defined as a 30% or greater reduction from baseline in morning peak expiratory flow on 2 consecutive days. Secondary end points included asthma control—measured by the Asthma Control Questionnaire-5 (ACQ-5)—and asthma quality of life or lung function.1,3

According to the findings, the study met its primary end point and demonstrated that treatment with the high (1200 mg) and low (800 mg) doses of rilzabrutinib resulted in a 36% (OR: 0.584 [0.253, 1.349]) and 25% (OR: 0.570 [0.202, 1.608]), respectively, relative risk reduction in LOAC at week 12. Additionally, there were nominally significant and clinically meaningful improvements in asthma symptoms (mean difference in ACQ-5: -0.54/-0.59 LS), which were seen as early as week 2.1

“We are incredibly encouraged by the reduction in loss of asthma control events and improvements in asthma symptoms and look forward to advancing rilzabrutinib into a broader phase 3 clinical development program to further explore its potential in this disease,” said Houman Ashrafian,executive vice president, head of Research and Development, Sanofi, in a press release. “Advanced oral therapies have the potential to change the treatment paradigm for diseases like asthma, and we remain committed to exploring disruptive mechanisms of action for people living with uncontrolled chronic inflammatory diseases.”1

According to the investigators, the safety profile was consistent with other research that evaluated rilzabrutinib. There were no events of cytopenia, hemorrhagic events, atrial fibrillation, or imbalance in liver function tests in the population treated with rilzabrutinib. Additionally, the most common treatment-emergent adverse event was diarrhea, which occurred in 10.9% and 9.4% of patients in the high and low rilzabrutinib dose groups, respectively, and 3.1% of patients in the low-dose placebo group. There were no reports of this treatment-emergent AE in the high-dose placebo group.1

“These results are encouraging as they show an improvement in asthma symptoms and a numerical reduction in LOAC events—important parameters in the treatment of this chronic respiratory condition that can significantly impact our patients’ daily lives,” said Laidlaw in the press release.1

1. Sanofi. Media Update: New results from rilzabrutinib phase 2 study show potential to be first advanced oral treatment for moderate-to-severe asthma. News release. May 22, 2024. Accessed May 22, 2024.
2. Sanofi. Press Release: Rilzabrutinib LUNA 3 phase 3 study met primary endpoint in immune thrombocytopenia. News release. April 23, 2024. Accessed May 22, 2024.
3. Proof of Concept Study of Rilzabrutinib in Adult Participants With Moderate-to-severe Asthma. identifier: NCT05104892. Updated March 7, 2024. Accessed May 22, 2024.
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