Dupixent eases flares, aids lung function with COPD: NOTUS trial
Findings in second Phase 3 study under FDA review for possible approval
Dupixent (dupilumab) as an add-on maintenance treatment significantly eased exacerbations and lung symptom severity while improving lung function and quality of life — among people with moderate to severe chronic obstructive pulmonary disease (COPD).
That’s according to published data from the Phase 3 NOTUS clinical trial (NCT04456673), which confirmed previous findings in the similarly designed Phase 3 BOREAS study (NCT03930732).
“In my more than 20 years of practice, there have been limited advancements for patients struggling with the debilitating effects of uncontrolled COPD, and too many patients experience a vicious cycle of exacerbations,” Surya Bhatt, MD, NOTUS’s co-principal investigator and a professor of medicine at the University of Alabama at Birmingham, said in a press release from Sanofi, which is developing Dupixent with Regeneron Pharmaceuticals.
“In NOTUS, [Dupixent] reduced exacerbations by a magnitude never seen before with an investigational biologic in a phase 3 COPD clinical study,” Bhatt said. “These comprehensive results reinforce that, if approved, [Dupixent] could provide a first-of-its-kind medical advancement for the COPD community.”
FDA decision on Dupixent as add-on COPD treatment due in September
NOTUS data were presented at the 2024 American Thoracic Society (ATS) International Conference in San Diego, and simultaneously published in the New England Journal of Medicine in the study, “Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation.”
Data from both BOREAS and NOTUS supported the filing of an application with the U.S. Food and Drug Administration (FDA) seeking to extend Dupixent’s label to include its use as an add-on treatment for adults with uncontrolled COPD, despite standard care, and signs of type 2 inflammation.
This type of inflammation, which is thought to contribute to COPD-related lung inflammation, is characterized by high counts of eosinophils, a type of immune cell normally responsible for combating certain infections, such as those caused by parasites.
While an FDA decision initially was expected by June 27, the submission of further trial data requested by the agency resulted in a three-month delay, giving the FDA time to review the additional findings before making a decision.
Similar regulatory applications are under review in China and in Europe, where a regulatory committee voted in favor of Dupixent’s label expansion.
A chronic inflammatory disease of the lungs, COPD causes symptoms such as cough with mucus, wheezing, and shortness of breath.
“COPD is the third leading cause of death globally,” Bhatt said in a separate university press release. Exacerbations, or periods of sudden symptom worsening, “lead to poorer quality of life, increased hospitalizations and an increased risk of death,” he added.
Trial in adults with moderate to severe COPD and type 2 inflammation
Dupixent, an antibody-based therapy designed to suppress type 2 inflammation, is approved in the U.S. for five other conditions marked by this type of inflammation. The treatment is expected to help ease respiratory symptoms in COPD patients with type 2 inflammation.
NOTUS enrolled 935 adults, ages 40-85, with moderate to severe COPD and evidence of type 2 inflammation. All were current or former smokers and had uncontrolled disease despite maximal standard-of-care inhaled therapy, including corticosteroids, long-acting beta agonists, and long-acting muscarinic antagonists (triple inhaled therapy).
Participants were randomly assigned to an under-the-skin injection of either Dupixent or a placebo every two weeks for up to one year, in addition to standard inhaled treatments.
The global study’s main goal was to determine changes in the frequency of COPD exacerbations. Several secondary outcomes included changes in lung function and in patient-reported lung symptom severity and quality of life.
Similar to findings in the BOREAS trial, Dupixent-treated patients experienced a significantly lower annualized rate of moderate or severe exacerbations than those on a placebo (0.86 vs. 1.30), representing a 34% difference.
Dupixent more than doubled the mean amount of air treated patients could forcibly exhale in one second, or FEV1, relative to those given a placebo (139 mL vs. 57 mL) after three months — meeting a secondary goal — and these improvements were maintained at one year (115 mL vs. 54 mL).
Compared with the placebo, Dupixent also led to an easing in respiratory symptom severity, as assessed with the Evaluating Respiratory Symptoms in COPD, and to improvements in health-related quality of life, measured using the St. George’s Respiratory Questionnaire. However, these group differences did not reach statistical significance.
Dupixent “substantially decreases exacerbation frequency and improves lung function as well as symptom burden in patients with COPD with type 2 inflammation and high exacerbation risk, who are already on maximal inhaled therapy,” Bhatt said.
Safety findings were generally consistent with Dupixent’s known safety profile. Common adverse events, more frequently reported with Dupixent than a placebo, included COVID-19 (9.4% vs. 8.2%), headache (7.5% vs. 6.5%), and the common cold (6.2% vs. 5.2%). More deaths related to adverse events were reported among patients given Dupixent (2.6% vs. 1.5%).
“The NOTUS trial showed that [Dupixent], when added to background triple inhaler therapy, reduced the annualized rate of moderate or severe exacerbations and improved lung function in patients with COPD and type 2 inflammation,” the researchers wrote.
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