Study Tests BTK Inhibitor for Poorly Controlled Asthma

The investigational Bruton’s tyrosine kinase (BTK) inhibitor rilzabrutinib was associated with numerical decreases in loss of asthma control events for patients with poorly controlled asthma, according to a randomized phase II trial reported at the recent American Thoracic Society annual meeting.

In this exclusive MedPage Today video, Leda Mannent, MD, global project head of immunology and inflammation at Sanofi, discusses the results and takeaways of the study.

Following is a transcript of her remarks:

This first study is a phase II study that was conducted with rilzabrutinib. It was a double-blind, placebo-controlled, randomized trial that was conducted in two cohorts.

The first cohort evaluated the 800-mg [dose], which was the low dose against placebo, and that was about 30 patients per arm. And then we had a second cohort that started a little bit later with a higher dose, and that was 1,200 mg compared to placebo.

So patients in both cohorts were treated for 12 weeks. And the interesting part of the design is that for the first 4 weeks, the patients … were on their inhaled corticosteroid and the controller that was long-acting beta agonist [LABA] for 4 weeks on top of either rilzabrutinib or placebo.

And then after 4 weeks, we started to withdraw their background therapy, first of all the LABAs. And then after week 6, we started to withdraw also their inhaled corticosteroids. So the study therefore allowed us to evaluate the effect of the study drug on top of the background therapy, but also while these therapies are withdrawn.

The first goal of the study was to see if — after this withdrawal — we will still be able to maintain a low rate of loss of asthma control. So, numerically in both cohorts, we could see that in patients treated with rilzabrutinib, there is fewer loss of asthma control compared to placebo. That was a 25% relative reduction for the low-dose cohort and a 36% reduction for the high-dose cohort.

The most interesting part of the study that we were really very nicely surprised by was the very fast impact on the symptoms that were evaluated through the ACQ-5 [the 5-item Asthma Control Questionnaire], but also in the quality of life that was evaluated through another Asthma Quality-of-Life Questionnaire, AQLQ. There was a very fast improvement from week 2 in the asthma symptoms across all five symptoms of the ACQ-5, and that was maintained despite withdrawal of their background therapy.

This effect on symptoms is unprecedented. It has never been seen with other drugs … so this really gives us a lot of excitement and enthusiasm as we are moving forward in the field of bringing new therapies for asthma. That is very important because many patients today, despite having multiple options — either inhaled corticosteroids or other inhaled controllers, or even with the advent of biologics that actually improved a lot of the control and the reduction in the exacerbation, especially for the severe asthma patient — there are many patients that across a different treatment algorithm are still left without any options for their symptoms.

And about 50% of the patients carry on every day with different symptoms. They have shortness of breath, they have wheeze, and they have limitation on their daily activities. So that was for the efficacy part of the study.

And then for the safety … rilzabrutinib in both doses was well tolerated. The main adverse events were GI events that actually disappeared after the first 4 weeks of treatment. But, overall, the treatment was well tolerated, without any off-target effects that have been usually reported with the old class of the BTK inhibitors. And that confirms also the safety results that have been seen with rilzabrutinib in other indications.

One of the most important pieces here is, what are we bringing to the science and what is the novelty of the data? And this is the first, very first time, that the BTK pathways are explored by clinical study in asthma. So they also open new avenues to the science to explore more of the role of this target in the pathophysiology of asthma. And I think that is also a very exciting part for all of us.

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