Dupilumab improves lung function and significantly reduces exacerbations in patients with difficult-to-control asthma, results from two phase 3 trials show.
The biologic allows us to treat "a group of patients with severe asthma that we were unable to treat before," said Mario Castro, MD, from the Washington University School of Medicine in St. Louis, who was involved in both studies.
"This is a whole new paradigm of treatment for asthma," he told Medscape Medical News.
Dupilumab is a monoclonal antibody directed against the alpha subunit of the interleukin (IL)-4 receptor that inhibits IL-4 and IL-13 signaling. It is not yet approved for the treatment of asthma, but the injectable drug was approved for eczema last year by the US Food and Drug Administration.
Castro presented results from a study of 1902 patients 12 years and older with uncontrolled asthma at the American Thoracic Society 2018 International Conference in San Diego. The results were published online simultaneously in the New England Journal of Medicine.
Patients were randomly assigned to dupilumab 200 mg, dupilumab 300 mg, or placebo every 2 weeks for 52 weeks.
Mean improvement in lung function with dupilumab was about 300 mL, "which doesn't sound like a lot, but you have to remember that these patients start off with very low lung function," Castro explained. In fact, forced expiratory volume in 1 second (FEV₁) was around 1.7 L at baseline, or a lung function of about 51%.
At 12 weeks, the increase in FEV₁ was better in the 200 mg group than in the placebo group (0.32 L vs 0.14 L; P < .001).
An improvement of 0.30 L is significant. "When we see that kind of change, we know patients are feeling better," Castro reported.
In the second study, also published online simultaneously in the New England Journal of Medicine, 210 patients with asthma were randomly assigned to dupilumab 300 mg or placebo every 2 weeks for 24 weeks while they continued to use oral glucocorticoids.
Asthma control was maintained from baseline to week 24, but the decrease in glucocorticoid use was greater in the dupilumab group than in the placebo group (70.1% vs 41.9%; P < .001).
In both trials, there was a significant reduction in the number of asthma exacerbations with dupilumab. The greatest benefit was seen in patients with high blood eosinophil counts.
There are patients who can reduce or get off steroids altogether, which is really exciting, Castro told Medscape Medical News.
The adverse effects of steroids include weight gain, fluid retention, hypertension, diabetes, and cataracts, "so it's really life-changing for them," he noted.
The drug also effectively improves lung function, in some cases, after just one dose, which is "something we've really been awaiting," he said.
With other biologic therapies, treatments are limited to predominantly allergy-driven asthma. But not all patients fit that criterion, said Castro, and "we are eager to see if we can reverse disease in those patients with this drug."
The data so far indicate that "dupilumab is a very effective therapy," said Michael Wechsler, MD, from the Cohen Family Asthma Institute at National Jewish Health in Denver.
"It reduces exacerbations and improves lung function beyond anything we've seen in biologic therapies," he told Medscape Medical News. And it is not just beneficial to eosinophilic patients. "It also benefits patients who have type 2 inflammations."
And dupilumab can be injected at home, so patients do not have to come into the office for treatment. "That has a big impact," he added.
Although dupilumab reduces exacerbations in patients with uncontrolled asthma, other biologics are effective too. Head-to-head comparisons will be needed to determine which are the most beneficial, Wechsler noted.
High Costs Mean Comparison Trials Needed
It is "likely that these data will lead to approval of dupilumab for the indication of severe asthma," Jeffrey Drazen, MD, and David Harrington, PhD, both from the Dana–Farber Cancer Institute in Boston, write in an editorial that accompanies the published studies.
When that happens, dupilumab will join three other biologics — mepolizumab, reslizumab, and benralizumab — approved for the treatment of asthma. But the annual cost of these drugs is currently about $30,000 to $40,000.
"With costs for a year of treatment substantially more than a year's labor at minimum wage in the United States, we deserve to know whether there are clinically important differences among these treatments," Drazen and Harrington explain.
The pair envisions a trial in which patients meeting specific asthma and biomarker criteria would be assigned randomly to one of the four active treatments.
"If we do not take the head-to-head approach, we will end up prescribing the treatment with the most effective marketing. Our patients deserve better than that," they conclude.
Castro, Drazen, and Harrington have disclosed no relevant financial relationships. Wechsler reports financial relationships with AstraZeneca, Boehringer Ingelheim, Boston Scientific, GlaxoSmithKline, Novartis, Regeneron Pharmaceuticals, Sanofi, and Teva Pharmaceuticals USA.
American Thoracic Society (ATS) 2018 International Conference: Abstract 421, presented May 20, 2018; late-breaking abstract B14, presented May 21, 2018.
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Cite this: Dupilumab Helps Lung Function, Reduces Asthma Exacerbations - Medscape - May 23, 2018.