Rilzabrutinib shows improvement in asthma control
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Key takeaways:
- Patients treated with rilzabrutinib saw a significant reduction in loss of asthma control events compared with the control group.
- The control group had higher treatment-emergent adverse events.
SAN DIEGO — Patients with moderate to severe asthma who were treated with rilzabrutinib showed a reduction in loss of asthma control events, according to a study presented at the American Thoracic Society International Conference.
Those patients also experienced a rapid and clinically meaningful improvement in asthma control over 12 weeks compared with the control group receiving placebo, Leda P. Mannent, MD, global project head, immunology and inflammation, Sanofi, and colleagues wrote.
“The treatment of asthma has evolved in the past decade, but despite being treated with standard-of-care therapies, including biologics, approximately 50% of the asthma patients still experience symptoms,” Mannent told Healio. “Lack of symptom control is one of the main reasons why patients continue to have exacerbations.”
The study evaluated the efficacy and safety of twice-daily and three-times-daily dosages of rilzabrutinib in a phase 2 proof-of-concept study, with this portion focusing on the results from the twice-daily cohort. The study was conducted for 12 weeks as a parallel-treatment, double-blind, placebo-controlled, two-staggered-cohort study. It included adults with moderate to severe asthma that was poorly controlled by using inhaled corticosteroids (ICS) and long-acting beta-2 adrenergic agonist (LABA) therapy.
A total of 64 patients were included in the study and randomly assigned 1:1 to 400 mg rilzabrutinib or placebo twice daily. Patients also received background therapy of medium to high doses of ICS or LABA, which was removed between weeks 4 and 9 and then resumed at end of treatment.
The primary endpoints of the study were the proportion of patients who experienced a loss of asthma control event during the study and a change from baseline in Asthma Control Questionnaire-5 (ACQ-5) scores.
“Treatment with high and low dose oral rilzabrutinib led to a numerical (36% and 25%) reduction in loss of asthma control (LOAC) events in adults with moderate to severe asthma who are not well controlled on ICS/LABA therapy,” Mannent said.
Results showed that the proportion of patients with an LOAC event over 12 weeks of treatment was 37.5% for rilzabrutinib and 50% for placebo (OR = 0.57; 95% CI, 0.202-1.608).
Significant improvement in ACQ-5 scores were observed in week 2 of treatment in the rilzabrutinib vs. placebo group (least squares [LS] mean, –0.74 vs. –0.20; difference, –0.54; 95% CI, –0.89 to –0.19) and lasted throughout week 12 (LS mean, –0.70 vs. –0.12; difference, –0.59; 95% CI, –1.07 to –0.1), even though ICS/LABA treatment had been withdrawn.
Treatment-emergent adverse events were more common in the placebo group than the rilzabrutinib group, with the most common by system organ class being infections, with rates higher for placebo (37.5%) than rilzabrutinib 800 mg (6.3%) and for rilzabrutinib 1200 mg (12.5%) and placebo (13.2%). In the low dose cohort, Nasopharyngitis and headache each affected 12.5% of the placebo group vs. 0% of the rilzabrutinib group.
“These data demonstrate that rilzabrutinib has the potential to be the first advanced oral treatment for moderate to severe asthma,” Mannent said. “The findings support the further development and advancement into a phase 3 clinical program in asthma, which will provide us with more information on the efficacy and safety of the drug.”
Researchers concluded that rilzabrutinib was generally safe and well tolerated in their study.
“The results are encouraging news for patients who continue to suffer from asthma symptoms, despite being treated with standard-of-care inhaled therapies,” Mannent said. “Poor asthma symptom control is a risk factor for exacerbations. The reduction in LOAC events, despite withdrawal of ICS and LABA background therapy, and rapid and meaningful improvement in asthma symptoms show rilzabrutinib’s potential to help prevent exacerbations.”