Dupixent found to prevent COPD exacerbations in Phase 3 trial
Chronic lung disease is 7th indication to show positive results
Dupixent (dupilumab) — a medication initially approved for exzema — was found to significantly reduce the number of disease exacerbations and to improve lung function in people with chronic obstructive pulmonary disease (COPD), meeting the primary and key secondary goals of the pivotal Phase 3 BOREAS trial.
A similarly designed study, the Phase 3 NOTUS trial (NCT04456673), is now seeking to replicate those findings. The trial aims to enroll 924 current or former smokers, ages 40-85, with moderate to severe COPD who have a high risk of experiencing an exacerbation despite being on maximum treatment. It’s recruiting at 351 locations worldwide.
First approved for eczema (atopic dermatitis) in 2017, the therapy from Regeneron Pharmaceuticals and Sanofi is now approved for five indications; the other four are asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis. All of these conditions are marked by a particular type of inflammation that Dupixent targets.
The treatment is not approved to treat COPD, but the chronic lung disease is now the seventh indication for which Dupixent has shown positive pivotal results.
It’s also the only biologic — a treatment derived from natural sources — to have led to such substantial benefits for COPD patients in a clinical trial, according to Regeneron.
Dupixent shows promise for treating COPD
“COPD is an urgent global health concern and a notoriously difficult-to-treat disease due to its heterogeneity, with no novel treatments approved in more than a decade,” George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron, and one of Dupixent’s inventors, said in a company press release.
“In this landmark Phase 3 trial, patients with uncontrolled COPD achieved clinical outcomes with Dupixent at a magnitude never before seen with a biologic,” Yancopoulos said, adding, “We look forward to discussing these exciting results with regulatory authorities.”
Dupixent is not a broad-acting immunosuppressant. Instead, it targets a specific type of inflammation that’s present in the diseases for which it is approved. That inflammation also is evident in COPD.
The antibody-based therapy inhibits interleukin-4 and interleukin-13, two signaling molecules thought to drive type 2 inflammation. This inflammation is a specific pattern of immune responses marked by an elevation of pro-inflammatory immune cells, called eosinophils, in the blood.
A significant proportion of COPD patients have elevated eosinophil levels in their lungs, which correlates with greater disease severity.
By dampening those immune responses, Dupixent may help ease respiratory symptoms in COPD patients with type 2 inflammation, its developers believe.
Given that Dupixent is already approved for a number of indications and has an established safety profile, the companies were able to jump directly to a Phase 3 trial for the COPD clinical program.
“We took a bold approach with our direct to Phase 3 program, shaving years off standard clinical development timelines,” said Dietmar Berger, MD, PhD, head of global R&D ad interim and chief medical officer of Sanofi.
“Change cannot come quick enough for people living with uncontrolled COPD,” Berger said.
The goal of the Phase 3 BOREAS trial (NCT03930732), for which results are now available, was to assess the safety and efficacy of Dupixent in 939 patients, ages 40-80, with moderate to severe COPD and evidence of type 2 inflammation.
All were current or former smokers and had uncontrolled disease with maximal standard of care inhaled therapies, including corticosteroids, long-acting beta agonists, and long-acting muscarinic antagonists.
Participants were randomly assigned to receive Dupixent or a placebo, given as an under-the-skin (subcutaneous) injection, once every two weeks, in addition to the triple combo of standard inhaled therapies.
The trial’s main goal was to assess changes in the frequency of COPD exacerbations — rapid and acute episodes of respiratory symptom worsening — over a year of treatment.
Dupixent led to a significant, clinically meaningful, 30% reduction in moderate or severe exacerbations compared with the placebo, meeting that goal.
Moreover, treatment led to significant improvements in lung function relative to the placebo by week 12, or about three months, which were sustained for a year, meeting key secondary goals.
In this landmark Phase 3 trial, patients with uncontrolled COPD achieved clinical outcomes with Dupixent at a magnitude never before seen with a biologic.
Improvements in patient-reported health-related quality of life and reductions in the severity of COPD respiratory symptoms relative to the placebo also were observed.
Safety findings were consistent with the known safety profile of Dupixent. Side effects more common with Dupixent than with the placebo included headache, diarrhea, and back pain.
Detailed findings will be presented at a future scientific forum, according to Regeneron. Data from NOTUS are expected in 2024. That trial is recruiting at 351 locations worldwide.
“We are excited to share these unprecedented and potentially paradigm-shifting clinical results, which may give new hope to patients, caregivers and physicians,” Berger said.
Yancopoulos noted that these findings also “validate the role type 2 inflammation plays in driving COPD in these patients, advancing the scientific community’s understanding of the underlying biology of this disease.”