Rilzabrutinib shows potential in patients with uncontrolled asthma

BTK inhibition with rilzabrutinib does not appear to significantly decrease the incidence of loss-of-asthma-control (LOAC) event compared with placebo in patients with moderate-to-severe asthma with uncontrolled symptoms, according to a phase II study. However, the investigational drug has been associated with meaningful symptom improvements over time, despite withdrawal of background therapy.

The phase II study included 310 patients with physician-diagnosed moderate-to-severe asthma for at least 12 months who had uncontrolled symptoms on inhaled glucocorticoids plus a long-acting β₂-adrenergic agonist.

The patients were randomly assigned to receive rilzabrutinib 800 mg (n=32) or matching placebo (n=32) (low-dose cohort) or rilzabrutinib 1,200 mg (n=64) or matching placebo (n=68) (high-dose cohort). Treatment was administered orally once a day. Background therapy was gradually withdrawn by weeks 4–9 and resumed at week 12.

The primary endpoint was LOAC event during treatment, while the key secondary endpoint was asthma control, assessed using the 5-item Asthma Control Questionnaire, in the modified intention-to-treat population. Safety was also assessed.

Over 12 weeks, LOAC events occurred in 38 percent of patients receiving rilzabrutinib 800 mg vs 50 percent of those receiving placebo (odds ratio [OR], 0.57, 95 percent confidence interval [CI], 0.20–1.61; p=0.29) and in 19 percent of those treated with rilzabrutinib 1,200 mg vs 29 percent of those who received placebo (OR, 0.58, 95 percent CI, 0.25–1.35; p=0.21).

Improvements with asthma control were observed as early as week 2 with rilzabrutinib vs placebo and sustained up to week 12 without background therapy (low-dose cohort: mean difference, –0.59; 95 percent CI, –1.07 to –0.10; p=0.018; high-dose cohort: mean difference, –0.54, 95 percent CI, –0.86 to –0.21; p=0.0013).

In terms of safety, diarrhoea was the most common adverse event with rilzabrutinib. There was no increase in infections observed with either dose of rilzabrutinib.