The Regeneron Pharmaceuticals and Sanofi-collaborated biologic became a tour de force in pulmonological care in 2019.
The asthma field welcomed a prominent new player in 2018. The US Food and Drug Administration (FDA) approved dupilumab (Dupixent) for the treatment of particular adults and adolescents aged 12 years or older with corticosteroid-dependent or eosinophilic asthma in October, marking its second indication for an inflammatory disease after atopic dermatitis (AD).
The Regeneron Pharmaceuticals and Sanofi-collaborated biologic became a tour de force in pulmonological care as of late, and American College of Allergy, Asthma & Immunology president Bradley Chipps, MD, previously told MD Magazine® it had the potential to alter the field before its approval.
“It will be a game-changer, because it's at-home after the first loading dose in an office, every 2 weeks, and it allows patients to decrease their corticosteroid dose, and also decrease the amount of medication they're taking,” Chipps explained.
As the only FDA-approved biologic that provides patients with an asthma treatment they can self-administer at home, dupilumab not only offers patients more convenient care, but it also raises the bar for asthma care expectations in general.
It’s also championed a new targeted attack that clinicians anticipate future biologics to follow. As an interleukin-4 and -13 (IL-4, IL-13) targeting drug, dupilumab is treating patient pathways responsible for allergic response and immunoglobulin E formulation and smooth muscle contraction, respectively. Both are critical targets in treating asthma symptoms, Monica Kraft, MD, Department of Medicine chair at the University of Arizona College of Medicine — Tuscon, told MD Mag this year.
“[It’s exciting] because they share a common receptor, the alpha 4 receptor 4, and so by targeting that receptor, you get both,” Kraft said. “Data has shown benefits in patients who have allergy and patients who have eosinophils or not. It targets a very large population of potential patients with severe asthma.”
Its benefits in the field are still being found. In a recent update from the LIBERTY ASTHMA trials evaluating dupilumab for the treatment of patients with an uncontrolled, moderate-to-severe form of the disease, investigators found that patients on 200 mg dupilumab experienced a 46.4% reduction in annualized severe exacerbation rates versus placebo.
Significant improvements in FEV1 from baseline to week 12 versus placebo were reported by both 200 mg and 300 mg treatment groups, 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).
Injection site reactions were the only adverse events that occurred in more than 10% of the adolescent patient population. In the 200 mg and 300 mg dupilumab groups, respectively, injection site reactions were reported in 9% and 10% of patients.Dupilumab's potential isn’t limited to asthma, though. After being approved for adults with AD in March 2017, the biologic is being studied in adult patients with poorly-controlled chronic rhinosinusitis with nasal polyps (CRSwNP).
In a phase 3 trial evaluating dupilumab for the treatment of moderate-to-severe AD, investigators found patients achieved 75% or greater skin improvement, as measured by Eczema Area and Severity Index (EASI-75) at week 15, plus the proportion of patients with an investigator global assessment (IGA) score of 0-1 at week 16 (on a five-point skin lesion severity scale ranging from 0 [clear] to 4 [severe]).
By the study’s end, 41.5% of patients administered dupilumab every 2 weeks achieved EASI-75, compared with 38% of patients administered therapy every 4 weeks, and just 8% of patients administered placebo (P < .001). Patients administered 2-week dupilumab doses also led in IGA-based skin lesion metrics—24% reached a score of 0-1, versus 18% of patients administered dupilumab every 4 weeks, and just 2% of patients administered placebo (P < .001).
Investigators also noted about two-thirds of treated patients (66% in 2-week patients; 65% in 4-week patients) reported improvements in EASI score from baseline after 16 weeks. All patients administered dupilumab reported significantly improved scores in quality of life scales, including the Children's Dermatology Life Quality Index (CDLQI) and patient-reported symptoms measured by the Patient-Oriented Eczema Measure (POEM), compared to patients administered placebo (P < .001).
“Limited treatment options leave adolescents with uncontrolled moderate-to-severe atopic dermatitis to cope with intense, unrelenting itch and skin lesions," said Amy S. Paller, MD, principal investigator director of the Northwestern University Skin Disease Research Center. With these new EADV findings, investigators have shown its benefit for the unbearable symptoms of AD that adolescents are subjected to.
In the SINUS-24 and SINUS-52 phase 3 pivotal trials evaluating dupilumab for the treatment of patients with poorly-controlled chronic rhinosinusitis with nasal polyps (CRSwNP), patients treated with dupilumab as an add-on therapy to corticosteroid nasal spray reported improvements, each above 50% (51%, 57%) in nasal congestion/obstruction over 24 weeks, compared to improvements of just 15% and 19% in patients treated with lone nasal spray and placebo.
Speaking on its benefits for patients with CRSwNP, Claus Bachert, MD, PhD, told MD Mag this year that treated patients were reportedly in much better shape than expected.
“We have a score out of 100 — the patient may feel like 75 out of 100, in terms of problems,” Bachert’s explained. “And that goes down to 10, which is an enormous difference. Those patients also profit from lowered airways, lung function getting better, better asthma control.”As dupilumab continues to take off in the United States, it also continues to stretch into other countries. In July 2017, the biologic was given a positive opinion by the Committee for Medicinal Products for Human Use (CHMP) for the AD indication, and the European Commission (EC) granted marketing authorization for dupilumab for the treatment of adults with moderate-to-severe AD who are candidates for systemic therapy. There is also a pending EC approval for dupilumab for the treatment of patients with inadequately controlled moderate-to-severe asthma.
However, geographical boundaries aren’t the only ones being broken. Physicians believe that dupilumab offers a potential treatment for varying allergic inflammatory diseases.
Specifically, George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron, 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.”
Echoing Yancopoulos, Kraft told MD Mag that dupilumab’s emergence comes in the middle of great change in the asthma field.
“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,” Kraft said.
Headed into 2019, patients and physicians will breathe easier knowing the new biologic is just getting started.
This article is part of MD Magazine's This Year In Medicine 2018 series. To read more from the series, check out the links below and follow us on Twitter at @MDMagazine.Finding and Treating the Young Hepatitis C Patient