The Potential Role of Dupilumab in COPD Management, with Antonio Anzueto, MD

As 2024 begins to wind to a close, the pulmonologists and the medical community prepare to enter the new year armed with additional options in their armamentarium for the management of chronic obstructive pulmonary disease (COPD).

Although the community welcomed the US Food and Drug Administration's approval of ensifentrine (Ohtuvayre) in June 2024, the addition of a biological option in dupilumab (Dupixent) has given pulmonologists and COPD specialists more reason to celebrate. Approved as an add-on formaintenance treatment of adults with inadequately controlled COPD and an eosinophilic phenotype on September 27, 2024, dupilumab became the first biologic medicine approved in the US to treat patients with COPD.^1,2

“I think we are providing our patients with more and more opportunities. I have patients with asthma that have been on biologicals for a while and the change that I have seen in their life and everything is a day to night difference,” said Antonio Anzueto, MD, professor of Medicine at UT Health San Antonio and section chief of Pulmonary at South Texas Veterans Healthcare System, in an interview with HCPLive. “So, [that] biologicals are going to be doing the same in COPD is going to be incredibly exciting.”

The September 2024 approval for dupilumab marks 3 approvals in 2024 and 9 approvals in the last 5 years for the biologic, which Regeneron boasts is the most prescribed biologic by pulmonologists in the US. The approval as an adjunct in uncontrolled COPD is based on data from the phase 3 BOREAS and NOTUS trials, which were published in the New England Journal of Medicine in May 2023 and May 2024, respectively.^3,4,5

BOREAS

BOREAS was the first of the 2 phase 3 trials conducted to support the application for dupilumab in uncontrolled COPD. A 52-week, international, double-blind, randomized, placebo-controlled trial conducted at 275 sites in 24 countries, the trial randomized 939 adults who were current or former smokers with COPD, blood eosinophils of 300 cells per µL or more, and aged 40 to 80 years in a 1:1 ratio to dupilumab or placebo therapy in addition to maximal standard-of-care inhaled therapy.^4,6

The primary endpoint of interest was the annualized rate of moderate or severe exacerbations of COPD during the 52-week trial period.^4,6

Results indicated use of dupilumab was associated with a 30% reduction in moderate or severe acute COPD exacerbations at 52 weeks (Rate ratio [RR], 0.70; 95% CI, 0.58 to 0.86; P = .0005). Further analysis suggested use of dupilumab was associated with improvement in lung function, with prebronchodilator FEV1 improving by a least-squares (LS) mean difference of 160 mL (95% CI, 126 to 195) from baseline to week 12 among the dupilumab arm relative to 77 mL (95% CI, 42 to 112) for placebo (LS mean difference, 83 mL; 95% CI, 42 to 125; P < .0001), with this benefit relative to placebo therapy sustained through week 52 (P = .0003).^4,6

In their press release announcing results from the trial, Regeneron pointed out met all endpoints tested in the hierarchy, including improvement in patient-reported health-related quality of life as measured by the St. George’s Respiratory Questionnaire (SGRQ) and reduction in the severity of respiratory symptoms of COPD as measured by Evaluation Respiratory Symptoms: COPD (E-RS: COPD) Scale.^4,6

NOTUS

Following the BOREAS trial, many looked ahead to the results of NOTUS, which was designed as a replicate of the BOREAS trial, with the exception of patients being aged 40 to 85 years in NOTUS. A 52-week, international, double-blind, randomized, placebo-controlled trial conducted at 329 sites in 29 countries, the trial randomized 935 adults with physician-diagnosed COPD for at least 12 months, blood eosinophils of 300 cells per µL or more, and aged 40 to 85 years in a 1:1 ratio to dupilumab or placebo therapy in addition to maximal standard-of-care inhaled therapy.^5,7

Like BOREAS, the primary endpoint of interest was the annualized rate of moderate or severe exacerbations of COPD during the 52-week trial period.

Results suggested use of dupilumab was associated with a 34% reduction in moderate or severe COPD exacerbations over 52 weeks (P <.001). Further analysis suggested use of dupilumab was associated with improvement in lung function, with prebronchodilator FEV1 improving by a LS mean difference of 139 mL (95% CI, 105 to 173) from baseline to week 12 with dupliumab as compared with a mean difference of 57 mL (95% CI, 23 to 91) placebo least-squares mean difference, 82 mL; 95% CI, 40 to 124; P <.001).^5,7

In their press release, Regeneron highlighted numerically greater improvements in health-related quality of life using the SGRQ and numerically greater reductions in respiratory symptom severity using the E-RS COPD Scale were observed in the trial.^5,7

“People living with inadequately controlled COPD have long awaited new medicines to help manage the daily suffering they experience from breathlessness, coughing, wheezing, exhaustion and unpredictable hospitalization. These patients often struggle with everyday activities many people take for granted such as taking a walk or running errands outside the home,” said Jean Wright, MD, chief executive officer at The COPD Foundation.² “We welcome the approval of this new therapeutic option to offer patients a new way to help gain better control of their disease.”

Relevant disclosures for Anzueto include GlaxoSmithKline, AstraZeneca, Regeneron, Boehringer Ingelheim, and others.

References:

1. Verona Pharma. Verona Pharma announces US FDA approval of OhtuvayreTM (Ensifentrine). Verona Pharma. June 26, 2024. Accessed September 30, 2024. https://www.veronapharma.com/news/verona-pharma-announces-us-fda-approval-of-ohtuvayre-ensifentrine/.
2. Regeneron Pharmaceuticals Inc. Dupixent® (dupilumab) approved in the U.S. as the first-ever biologic medicine for patients with COPD. Regeneron Pharmaceuticals Inc. September 27, 2024. Accessed September 30, 2024. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-approved-us-first-ever-biologic-medicine.
3. Stewart J. Dupixent (dupilumab) FDA approval history. Drugs.com. January 29, 2024. Accessed September 30, 2024. https://www.drugs.com/history/dupixent.html.
4. Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts. N Engl J Med. 2023;389(3):205-214. doi:10.1056/NEJMoa2303951
5. Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation. N Engl J Med. 2024;390(24):2274-2283. doi:10.1056/NEJMoa2401304
6. Regeneron Pharmaceuticals Inc. Dupixent® (dupilumab) demonstrates potential to become first biologic to treat COPD by showing significant reduction in exacerbations in pivotal trial. Regeneron Pharmaceuticals Inc. March 23, 2023. Accessed September 30, 2024. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-demonstrates-potential-become-first-biologic.
7. Regeneron Pharmaceuticals Inc. Dupixent® (dupilumab) late-breaking data from Notus Confirmatory Phase 3 COPD trial presented at ATS and published in the New England Journal of Medicine. Regeneron Pharmaceuticals Inc. May 20, 2024. Accessed September 30, 2024. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-late-breaking-data-notus-confirmatory-phase.