Three Trials Examine Dupilumab in Moderate-to-Severe Asthma

Three abstracts evaluating dupilumab (Dupixent) for moderate-to-severe asthma were presented at the recent American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting:

VESTIGE, a phase IV trial which evaluated the effect of dupilumab on airway remodeling parameters through the use of functional respiratory imaging; TRAVERSE, an open-label extension study that looked at the long-term safety and efficacy of dupilumab; and QUEST, a post-hoc analysis that evaluated potential advantages of dupilumab over inhaled corticosteroid (ICS) dose escalation.

In this first of four exclusive episodes, MedPage Today brought together three expert leaders in the field — moderator Michael Wechsler, MD, of National Jewish Health in Denver, is joined by Flavia Hoyte, MD, also of National Jewish Health, and Leonard Bacharier, MD, of Vanderbilt University Medical Center in Nashville, Tennessee — for a virtual roundtable discussion on the encouraging new data from these dupilumab studies.

Following is a transcript of their remarks:

Wechsler: Hello and welcome to this roundtable discussion on exciting findings from the American Academy of Allergy, Asthma & Immunology in 2024 that took place in February in Washington, D.C. I’m Dr. Michael Wechsler, professor of medicine at National Jewish Health in Denver, Colorado. And I’m joined today by two of my colleagues, Dr. Leonard Bacharier, who is a professor of pediatrics and an allergist and immunologist at Vanderbilt University, and by Dr. Flavia Hoyte, who is also an allergist and professor of medicine at National Jewish Health in Denver, Colorado. So, welcome both of you today.

I’m really excited to talk about many of the exciting findings that took place at the AAAAI this year. And I also want to thank our sponsor, MedPage Today, for bringing us all together.

The American Academy of Allergy, Asthma & Immunology, when we met last month, had many exciting studies reported about asthma, about steroid reduction, and about many of the biologics, as well as about EGPA — eosinophilic granulomatosis with polyangiitis. So we’re going to go through a few of these today and we’ll have each of us comment.

We’ll start off by talking about the VESTIGE trial. The VESTIGE clinical trial was a phase IV randomized double-blind placebo-controlled study that evaluated the efficacy of dupilumab on both lung inflammation and structural and functional changes in the airway volumes using novel imaging technologies, along with looking at safety in 109 individuals with asthma age 21 to 70 years.

And the key findings from that study were that about 57% of patients taking dupilumab achieved a significant reduction in airway inflammation as measured by exhaled nitric oxide, getting down to less than 25 parts per billion compared to only about 11% of patients on placebo. That was the primary endpoint.

But the other exciting findings, I think, were the fact that there were greater reductions in mucus plug scores compared to placebo, and dupilumab seemed to reduce not only mucus plug scores, but also improve lung function. So I thought we should talk a little bit about this.

Flavia, do you want to comment on the importance of all of these key findings, the reduction in nitric oxide, the reduction in mucus plug scores, and improvement in lung function?

Hoyte: Sure. I mean, we know that dupilumab works well, right, from the pivotal trials. We know it has a strong effect on exhaled nitric oxide and improves lung function, 200 mL’s approximately on average. But I think where this study is really novel is using these new imaging techniques and thinking about things like airway resistance and other ways of thinking about lung function and in particular mucus plugging. It’s something that we haven’t really talked too much about with these biologics, but it’s something that’s super relevant for our patients with asthma. And we know that mucus plugging is related to increased medication use and increased exacerbations, decreased lung function. And so having an impact on mucus plugging as kind of its own endpoint, I think is a really important and novel finding here.

Wechsler: Yeah, I agree. I think the use of these 3D visualizations is really novel and allows us to track asthma disease progression and also gives us a sense that we’re getting tremendous efficacy of the new biologic therapies with much greater accuracy than with traditional methods like spirometry. So that’s, I think, one exciting novel study.

There were also a lot of looks at some of the other data from QUEST and from the TRAVERSE study that were presented at the AAAAI. One of those studies was looking at more slicing and dicing, looking at all the different subgroups of patients who participated in the QUEST and long-term TRAVERSE study. And there seemed to be a significant reduction in exacerbations, no matter which patient population we looked at, whether it was obese patients or non-obese patients, whether patients were studied in North America and Europe or elsewhere, whether patients started off with low lung function or higher lung function, whether patients have higher nitric oxide, lower nitric oxide, it seemed no matter how we slice the data, dupilumab seemed to work quite well.

Len, do you want to comment a little bit about any of the post-talk QUEST and or TRAVERSE analysis and the importance of using this type of biologic therapy for our patients with type 2 asthma in particular?

Bacharier: Sure, Mike. So this has become very interesting and very informative as we continue to take many of these after-the-fact looks at these datasets. And one of the ones that was reported was an effort to try to understand at a very preliminary level whether the addition of dupilumab to patients who were uncontrolled receiving a moderate dose of inhaled corticosteroids led to an improvement and how that compared to patients who were maintained on a high dose of inhaled corticosteroids.

And this isn’t the way you would normally do this type of analysis because these patients weren’t randomized. One group received dupilumab on top of medium dose and one group was already uncontrolled on high dose and didn’t receive a step-up. But what was clear is that the addition of dupilumab to the moderate-dose ICS patients led to better control over the year, then patients were allowed to continue on a high dose of ICS without the addition of dupilumab.

Again, this does not sort of lead to the conclusion that adding dupilumab is superior to increasing to high dose — that needs to be studied in a prospective fashion, but I think it sets up the premise that that type of relationship might really exist, and may sort of open our panel of indications for which patients might be most appropriate for the addition of biologics, which has always been felt to represent only those on high-dose ICS. But we know about flat dose-response curves related to ICS. So I think it is more hypothesis-generating than conclusion-determining, but I think it points us in the right direction.

Wechsler: Yeah, I think all of these data are really reassuring to us as we provide biologic therapies to our patients with asthma, and I think they’re encouraging. I think that one of our goals is to try to offer precision-based medicine to our patients, and I think these data, again, support offering some of the biologic therapies to our patients with more severe disease, maybe even less severe disease. And I think as time evolves, we will have a better appreciation of which patients will benefit from which of these therapies most.

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