Pooled BOREAS, NOTUS analysis: Dupilumab beneficial in COPD with type 2 inflammation

Key takeaways:

• At 52 weeks, patients receiving dupilumab vs. placebo had a lower annualized exacerbation rate and improved lung function.
• Dupilumab continued to be found well tolerated in this patient population.

Dupilumab led to improvement and was safe in adults with moderate to severe COPD and type 2 inflammation at week 52, according to a pooled analysis of BOREAS and NOTUS presented at the European Respiratory Society International Congress.

Surya P. Bhatt

“The pooled analyses of the phase 3 BOREAS and NOTUS trials comprehensively demonstrate the efficacy and safety of dupilumab for patients with COPD and type 2 inflammation,” Surya P. Bhatt, MD, professor in the division of pulmonary, allergy and critical care medicine at The University of Alabama at Birmingham, told Healio.

“These robust results indicate that dupilumab may be an effective option for the high number of patients we see in clinical practice who continue to suffer exacerbations despite optimization of controller inhalers,” Bhatt continued.

As Healio previously reported, outcomes from the multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 NOTUS study confirmed findings from the multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 BOREAS study.

“BOREAS and NOTUS had almost identical trial designs and had similar findings,” Bhatt said.

Both studies assessed current/former smokers with moderate to severe COPD and type 2 inflammation (blood eosinophil count 300 cells/μL) primarily receiving background and stable triple therapy to see if 300 mg dupilumab every 2 weeks reduced the annual exacerbation rate over 52 weeks.

Pooling data from the BOREAS and NOTUS studies, Bhatt and colleagues assessed 1,874 adults with moderate to severe COPD and type 2 inflammation who were current or former smokers to find out the impact of dupilumab on exacerbations and lung function vs. placebo, as well as the drug’s safety profile in a larger population.

At randomization, 938 patients received dupilumab and 936 patients received placebo.

Compared with patients on placebo, patients on dupilumab showed a 31% decrease in the annualized moderate/severe exacerbation rate at week 52 (0.794 vs. 1.156; nominal P < .0001), according to researchers.

“Pooling the participants from these two trials allowed testing the efficacy of dupilumab for less frequent events such as severe exacerbations, which were numerically lower with dupilumab therapy,” Bhatt told Healio.

“In addition, the larger sample size allowed evaluating dupilumab’s efficacy in several important subgroups,” Bhatt said. “For instance, treatment with dupilumab was almost equally effective in those who were no longer smoking cigarettes vs. those who continued to smoke.”

Between baseline and week 12, researchers also observed a larger positive change in prebronchodilator FEV₁ in the dupilumab vs. the placebo group (least squares mean difference, 83 mL; nominal P < .0001). The same was true when analyzing changes between baseline and week 52, with a larger change observed among those receiving dupilumab (least squares mean difference, 73 mL; nominal P < .0001).

In terms of safety, a similar proportion of patients reported a treatment-emergent adverse event in both groups (dupilumab, 72.1% vs. placebo, 71%).

Several of these events occurred in 5% or more of both those receiving dupilumab and those receiving placebo, including COVID-19 infection (6.9% vs. 7.1%), upper respiratory tract infection (5.3% vs. 6.1%), headache (7.8% vs. 6.6%), COPD (5.3% vs. 6.9%), nasopharyngitis (7.8% vs. 7.4%) and accidental overdose (6.1% vs. 6.6%).

Additionally, researchers observed a comparable number of deaths due to an adverse event in the dupilumab and placebo groups (n = 19 vs. n = 15).

“Dupilumab has been approved for use in Europe for the specific endophenotype of type 2 inflammation and frequent exacerbations,” Bhatt told Healio. “This will markedly alter the therapeutic landscape for COPD, a disease for which we have had very few treatment options.”

Reference:

• Latest Dupixent (dupilumab) and itepekimab data at ERS highlight scientific innovation and leadership in respiratory disease. https://investor.regeneron.com/news-releases/news-release-details/latest-dupixentr-dupilumab-and-itepekimab-data-ers-highlight. Published Aug. 26, 2024. Accessed Aug. 29, 2024.