Dupilumab Potent Against Uncontrolled COPD with T2 Inflammation: BOREAS Trial Update

In adults with uncontrolled chronic obstructive pulmonary disease (COPD) and evidence of type 2 inflammation, the biologic agent dupilumab was associated with a 30% reduction in the annualized rate of disease exacerbations compared to placebo as well as with rapid and significant improvement in lung function, quality of life (QoL) and COPD respiratory symptoms.¹

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The findings, from the pivotal phase 3 BOREAS clinical trial,¹ were presented at the European Respiratory Society International Congress in Milan, Italy.

Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, now widely understood to be key drivers of type 2 inflammation. There are currently no biologic agents approved to treat COPD.

Led by Surya P Bhatt, MD, MSPH, associate professor in the University of Alabama at Birmingham’s Division of Pulmonary, Allergy and Critical Care Medicine, the BOREAS phase 3, randomized, double blind clinical trial enrolled 939 adults aged 40 to 80 years who were current or former smokers with uncontrolled moderate-to severe COPD. All study participants had evidence of type 2 inflammation as indicated by a blood eosinophil count of ≥300 cells/µL.

All participants were receiving maximal standard of care, ie triple therapy comprised of an inhaled corticosteroid (ICS), long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA). Investigators also accepted participants treated with a LABA/LAMA combination in cases where ICS was shown to be contraindicated.¹

Mean age of participants was 65.1 years; 66% were men; 84.1% were white.

Researchers randomly assigned participants receive dupilumab 300 mg (n=468) or placebo (n=471) every 2 weeks over the 52-week study period. The study’s primary endpoint evaluated the annualized rate of acute moderate or severe COPD exacerbations; key secondary endpoints included change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV₁) at 12 and 52 weeks; change from baseline at 52 weeks in QoL as measured by the St George’s Respiratory Questionnaire (SGRQ); and, change from baseline at 52 weeks in severity of COPD respiratory symptoms as measured by the Evaluation Respiratory Symptoms: COPD (E-RS: COPD) Scale.

FINDINGS¹

Exacerbations down. Bhatt and colleagues reported that compared with participants who received placebo, BOREAS participants who received dupilumab experienced a 30% reduction in annualized moderate or severe acute COPD exacerbations over 52 weeks (P=.0005), the study’s primary endpoint.

Increased FEV₁. Analyses of key secondary endpoints related to lung function also favored dupilumab, with an increase in prebronchodilator FEV₁ from baseline to week 12 by least squares (LS) mean of 160 mL at 12 weeks compared to 77 mL for placebo (LS mean difference, 83 ml; 95% CI, 42 to 125; P<.001), with the benefit versus placebo sustained through week 52 (P=.0003).

Improved QoL, symptoms. Participants in the dupilumab group also reported improved QoL, demonstrated by improvement at week 52 in SGRQ score by LS mean of −9.7 (95% CI, −11.3 to −8.1) vs −6.4 (95% CI, −8.0 to −4.8) with placebo (LS mean difference, −3.4; 95% CI, −5.5 to −1.3; P=.002), and a reduction in COPD symptom burden, as seen in improvement in E-RS–COPD score at 52 weeks by LS mean of −2.7 (95% CI, −3.2 to −2.2) with dupilumab and −1.6 (95% CI, −2.1 to −1.1) with placebo (LS mean difference, −1.1; 95% CI, −1.8 to −0.4; P=.001).

Reduced systemic corticosteroids. Bhatt et al also reported diminished use at week 52 of systemic corticosteroids for treatment of COPD exacerbations in the dupilumab-treated participants, measured as a reduction in days of use compared with placebo-treated participants.

Safety. Findings on the safety of dupilumab in COPD patients were consistent with drug’s known safety profile in its approved indications. Overall adverse event rates were balanced between treatment groups, at 77% for dupilumab and 76% for placebo with headache, diarrhea, and back pain more commonly observed with dupilumab.¹

In a statement earlier this year from dupilumab codeveloper Regeneron, George D Yancopoulos, MD, PhD, Regeneron president and chief scientific officer said, “In this landmark phase 3 trial, patients with uncontrolled COPD achieved clinical outcomes with Dupixent at a magnitude never before seen with a biologic. These results 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.”²

References

1. Bhatt SP, Rabe K, Hanania NA, et al; for the BOREAS Investigators. Efficacy and safety of dupilumab for COPD with type 2 inflammation indicated by elevated eosinophils. Paper presented at: European Respiratory Society (ERS) International Congress 2023; September 9 – 13. Milan, Italy. Accessed September 14, 2023.

2. Halsey G. Dupilumab achieves outcomes in phase 3 COPD clinical trial "never before seen with a biologic." Patient Care. March 4, 2023. Accessed September 15, 2023. https://www.patientcareonline.com/view/dupilumab-achieves-outcomes-in-phase-3-copd-clinical-trial-never-before-seen-with-a-biologic-