
- First biologic to demonstrate clinically meaningful and statistically significant reduction (30%) in exacerbations compared to placebo.
- First biologic to show rapid and significant improvement in lung function (160 mL in FEV1) compared to placebo (77 mL in FEV1).
- First biologic to demonstrate significant improvements in quality of life and respiratory symptoms.
- Trial enrolled patients with moderate to severe disease and evidence of type 2 inflammation (i.e., blood eosinophils ≥300 cells/μL).
Regeneron Pharmaceuticals, Inc. and Sanofi announced the primary and all key secondary endpoints were met in a phase 3 trial evaluating the investigational use of Dupixent (dupilumab) compared to placebo in adults currently on maximal standard-of-care inhaled therapy (triple therapy) with uncontrolled COPD and evidence of type 2 inflammation. Dupixent is the first biologic to demonstrate a clinically meaningful and highly significant reduction (30%) in moderate or severe acute exacerbations of COPD (rapid and acute worsening of respiratory symptoms) over 52 weeks, while also demonstrating significant improvements in lung function, quality of life and COPD respiratory symptoms.
“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,” said George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron, and a principal inventor of Dupixent. “In this landmark phase 3 trial, patients with uncontrolled COPD achieved clinical outcomes with Dupixent at a magnitude never before seen with a biologic. George D. Yancopoulos, MD, PhD
COPD is a life-threatening respiratory disease that damages the lungs and causes progressive lung function decline. Symptoms include persistent cough and breathlessness that may not only impair the ability to perform routine daily activities, but can also lead to anxiety, depression and sleep disturbances. COPD is also associated with a significant health and economic burden due to recurrent acute exacerbations that require systemic corticosteroid treatment and/or lead to hospitalization or even death. Smoking is a key risk factor for COPD, but even individuals who quit smoking can still develop the disease. In the U.S. alone, approximately 300,000 people live with uncontrolled COPD with type 2 inflammation.
“Change cannot come quick enough for people living with uncontrolled COPD, but unfortunately, many investigational treatments have failed to demonstrate significant clinical outcomes leaving these vulnerable patients with limited treatment options. 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 and interim at Sanofi and chief medical officer. Dietmar Berger, MD, PhD
In the BOREAS trial (the first of two phase 3 trials), 939 adults who were current or former smokers aged 40 to 80 years were randomized to receive Dupixent (n=468) or placebo (n=471) added to maximal standard-of-care inhaled therapy. Patients receiving Dupixent experienced:
- 30% reduction in moderate or severe acute COPD exacerbations over 52 weeks (p=0.0005), the primary endpoint.
- Improved lung function from baseline by 160 mL at 12 weeks compared to 77 mL for placebo (p<0.0001), with the benefit versus placebo sustained through week 52 (p=0.0003), both of which were key secondary endpoints.
Dupixent 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.
The safety results were generally consistent with the known safety profile of Dupixent in its approved indications. Overall rates of adverse events were 77% for Dupixent and 76% for placebo. Adverseevents more commonly observed with Dupixent compared to placebo included headache (8.1% Dupixent, 6.8% placebo), diarrhea (5.3% Dupixent, 3.6% placebo) and back pain (5.1% Dupixent, 3.4% placebo). Adverse events more commonly observed with placebo compared to Dupixent included upper respiratory tract infection (9.8% placebo, 7.9% Dupixent), hypertension (6.0% placebo, 3.6% Dupixent) and COVID-19 (5.7% placebo, 4.1% Dupixent). Adverse events leading to deaths were balanced between the two arms (1.7% placebo, 1.5% Dupixent).
The broader Sanofi and Regeneron COPD clinical research program includes phase 3 trials with itepekimab, a fully human monoclonal antibody that binds to and inhibits interleukin-33 (IL-33). Itepekimab received fast track designation from the U.S. Food and Drug Administration in January 2023 for the treatment of COPD in patients who do not currently smoke. Data from this pivotal program is expected in 2025.
About the Dupixent COPD phase 3 trial program
BOREAS is one of two pivotal trials in the Dupixent COPD program. The randomized, phase 3, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent in 939 adults who were current or former smokers aged 40 to 80 years with moderate to severe COPD. All patients in the trial had evidence of type 2 inflammation, as measured by blood eosinophils ≥300 cells/µL. During the 52-week treatment period, patients received Dupixent or placebo every two weeks added to a triple therapy of inhaled corticosteroids (ICS), long-acting beta agonists, and long-acting muscarinic antagonists. Double maintenance therapy was allowed if ICS was contraindicated.
The primary endpoint evaluated the annualized rate of acute moderate or severe COPD exacerbations. Moderate exacerbations were defined as those requiring systemic steroids and/or antibiotics. Severe exacerbations were defined as those: requiring hospitalization; more than a day of observation in an emergency department or urgent care facility; or resulting in death. Key secondary endpoints included: change from baseline in lung function (assessed by pre-bronchodilator forced expiratory volume [FEV1]) at 12 and 52 weeks; change from baseline at 52 weeks in SGRQ total score compared to placebo; the proportion of patients with SGRQ improvement ≥4 points at 52 weeks; and the change from baseline at 52 weeks in the ERS: COPD Scale symptom score.
The second, replicate phase 3 trial of Dupixent in COPD (NOTUS) is ongoing with data expected in 2024.
About Regeneron and Sanofi’s COPD clinical research program
Regeneron and Sanofi are motivated to transform the treatment paradigm of COPD by examining the role different types of inflammation play in the disease progression through the investigation of two potentially first-in-class biologics, Dupixent and itepekimab.
Dupixent inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways, and the program focuses on a specific population of people with evidence of type 2 inflammation. Itepekimab is a fully human monoclonal antibody that binds to and inhibits interleukin-33 (IL-33), an initiator and amplifier of broad inflammation in COPD. Across both programs, four phase 3 trials are ongoing and designed to inform next-generation treatments for people with COPD who might not have other options.