FDA Approves Dupilumab For Asthma Add-On Therapy

The US Food and Drug Administration (FDA) has approved dupilumab (Dupixent) as an add-on maintenance therapy for adults and adolescents aged 12 years or older, with an eosinophilic phenotype or with oral corticosteroid-dependent asthma.

The human monoclonal antibody biologics from Regeneron Pharmaceuticals and Sanofi, highlighted by its interleukin 4 and 13 (IL-4, IL-13) inhibition capabilities, has now been approved for 2 inflammatory condition indications—and is being investigated for another 3 more.

With the approval, dupilumab becomes the only biologic approved for oral corticosteroid-dependent asthma, regardless of phenotype, and the only asthma biologic that offers patient self-administration at home.

The FDA’s acceptance of its initial supplemental biologics application earlier this year was based on the findings from a trio of pivotal trials in the companies’ clinical development LIBERTY ASTHMA program, in which investigators assessed dupilumab’s effect on a patient population of 2888 adults and adolescents with uncontrolled asthma.

Study results shared in September 2017 reported comparable benefits for both 200 mg and 300 mg dupilumab’s treatment of asthma exacerbations and forced expiratory volume over 1 second (FEV₁). In yearlong treatment results (52 weeks), patients receiving 300 mg therapy reported a mean 46% reduction in severe asthma attacks. Among patients with at least 150 or 300 eosinophilic cells/mL, 60% and 67% reported a reduction in severe asthma attacks, respectively (P < .001).

At the time of the data release, George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron, noted the findings further supported the suggestion that the IL-4/IL-13 pathway is a “critical driver of allergic disease.” Dupilumab was approved in 2017 for the treatment of adults with moderate-to-severe atopic dermatitis (AD) previously not properly controlled with topical therapies.

In a recent assessment of 107 adolescent patients with uncontrolled asthma aged 12-17 years old from the LIBERTY ASTHMA trials, investigators found that patients on 200 mg dupilumab had a 46.4% reduction in annualized severe exacerbation rates versus placebo. A small sample size of patients on 300 mg therapy may have inhibited them from reporting a significant treatment effect versus those on placebo, but investigators also noted they also reported fewer prior exacerbation events (1.53) in the past year than patients on placebo (2.22).

Both dupilumab treatment groups did manage to report significant improvements in FEV₁ from baseline to week 12 versus placebo. The 200 mg patients (.36 [95% CI: .12 - .61]) fared better than 300 mg patients (.27 [95% CI: .02 - .52]), though all adolescents treated with dupilumab reported greater FEV₁ than treated adults from the LIBERTY ASTHMA trials (.12 [95 CI%: .07 - .18] for both 200 and 300 mg; P < .05).

The only adverse event to have occurred in more than 10% of the adolescent patient population was injection site reactions—it was reported in 9% and 0% of the 200 mg and 300 mg dupilumab groups, respectively.

Along with these data on reduced adolescent lung function, dupilumab has recently shown benefits for adolescent AD and poorly-controlled chronic rhinosinusitis with nasal polyps (CRSwNP) in adult patients.

Dupilumab’s two-fold targeting capabilities is a trait Monica Kraft, MD, highlighted in an interview with MD Magazine® while at the 2018 CHEST Annual Meeting in San Antonio TX. Kraft, the Department of Medicine chair at the University of Arizona College of Medicine — Tuscon, said dupilumab’s inhibition of IL-4 and IL-13’s mutual receptor addresses the cornerstone issues of allergic, inflammatory diseases.

“IL-4 is really important in the allergic response, in immunoglobulin E formulation, and that side of things,” Kraft explained. “IL-13 has a lot of effects on the airway, in terms of collagen deposition. It affects smooth muscle, increases contraction of smooth muscle, increases production of mucus—all the things that are abnormal in the asthmatic airway.”

Kraft added that current biologics seeking asthma indications—including tezepelumab, an epithelial cell inhibitor that could reach the market by next year&mdash;are representative of the improving clinical understand of the disease and its future treatment.

“The asthma world is very busy right now,” Kraft said. “I think we've developed a real understanding of the immunology of the disease and then in so doing, what therapies have been developed targeting specific inflammatory pathways.”

Following the release of phase 3 pivotal results for its treatment of adults with CRSwNP earlier this week, Yancopolous expressed the company’s intent to continue developing dupilumab programs for Type 2 or allergic inflammatory diseases with high unmet needs, including “pediatric asthma, pediatric and adolescent atopic dermatitis, eosinophilic esophagitis, and food and environmental allergies.”