The European Commission has approved Dupixent as an add-on treatment for adults with uncontrolled COPD.
RT’s Three Key Takeaways:
- European Approval for COPD: The European Commission has approved Dupixent (dupilumab) as an add-on maintenance treatment for adults with uncontrolled chronic obstructive pulmonary disease (COPD) characterized by raised blood eosinophils.
- Clinical Trial Success: The approval is based on positive results from the phase 3 BOREAS and NOTUS trials, which demonstrated significant reductions in COPD exacerbations, improvements in lung function, and enhanced health-related quality of life for patients treated with Dupixent.
- Global Regulatory Submissions: Additional regulatory submissions for Dupixent are under review in the United States, China, Japan, and other countries, indicating a potential global expansion of its use for COPD patients.
Regeneron Pharmaceuticals Inc and Sanofi announced that the European Commission has approved Dupixent (dupilumab) as an add-on maintenance treatment for adults with uncontrolled chronic obstructive pulmonary disease (COPD) characterized by raised blood eosinophils.
Specifically, the approval covers patients already on a combination of an inhaled corticosteroid, a long-acting beta2-agonist, and a long-acting muscarinic antagonist, or on a combination of a long-acting beta2-agonist and a long-acting muscarinic antagonist if inhaled corticosteroid is not appropriate.
The European Commission is the first regulatory authority in the world to approve Dupixent for COPD patients. Additional submissions are under review with other regulatory authorities around the world, including in the United States, China and Japan.
In the United States, Dupixent is approved to treat several conditions: atopic dermatitis, asthma, chronic rhinosinusitis, eosinophilic esophagitis, and prurigo nodularis.
Approval Significance and Expert Insights
“The approval of Dupixent for COPD is a long-awaited turning point for those who struggle to breathe even through the simplest of tasks, while also facing the risk of hospitalization, irreversible health decline, and feelings of hopelessness,” says George D. Yancopoulos, MD, PhD, board co-chair, president and chief scientific officer at Regeneron, and a principal inventor of Dupixent, in a release. “With this approval, we are proud that Dupixent has the potential to redefine the treatment landscape in yet another disease, as a first-in-class therapy demonstrating unprecedented improvements on exacerbations and lung function, as well as improving health-related quality of life across two large phase 3 trials.”
The approval is based on results from the phase 3 BOREAS and NOTUS trials, which were separately published in the New England Journal of Medicine and evaluated the efficacy and safety of Dupixent in adults with uncontrolled COPD with evidence of type 2 inflammation (ie, blood eosinophils ≥300 cells per μL). All patients were on background maximal standard-of-care inhaled therapy (with nearly all on triple therapy).
Clinical Trial Findings
In terms of efficacy, Dupixent patients in BOREAS (n=468) and NOTUS (n=470) experienced the following, respectively, compared to placebo (BOREAS n=471; NOTUS n=465):
- 30% and 34% reduction in the annualized rate of moderate or severe COPD exacerbations over 52 weeks, the primary endpoint.
- Improvements in lung function (pre-bronchodilator FEV1) from baseline by 160 mL and 139 mL at 12 weeks compared to 77 mL and 57 mL. These improvements were observed as early as week two and four and were sustained at 52 weeks in both trials.
- Improvements in health-related quality of life (statistically significant in BOREAS and nominally significant in NOTUS), as assessed by the St. George’s Respiratory Questionnaire (SGRQ).
Reductions in exacerbations and improvements in lung function for Dupixent versus placebo were also observed in patients with higher baseline fractional exhaled nitric oxide (FeNO; ≥20ppb)—an airway biomarker of inflammation—and across all pre-defined subgroups including smoking status, baseline lung function and history of exacerbations.
Safety Profile and Future Prospects
Safety results in both trials were generally consistent with the known safety profile of Dupixent in its approved indications. The most common side effects across indications include injection site reactions, conjunctivitis, conjunctivitis allergic, arthralgia, oral herpes, and eosinophilia.
Adverse events more commonly observed with Dupixent (≥5%) compared to placebo in either COPD trial were back pain, COVID-19, diarrhea, headache, and nasopharyngitis. Additional adverse reactions of injection site bruising, injection site induration, injection site rash, and injection site dermatitis were reported in the COPD trials.
“Patients with uncontrolled COPD have been waiting for a new treatment approach for many years, so we are thrilled to bring to market the first biologic to target an underlying cause of this devastating disease to reduce COPD exacerbations and improve lung function,” says Paul Hudson, chief executive officer at Sanofi, in a release. “With today’s approval of Dupixent, we can change the treatment landscape for the more than 200,000 patients throughout the [European Union] living with uncontrolled COPD with raised blood eosinophils. We look forward to working with other regulators around the world as quickly as possible to bring this novel treatment approach to patients in more countries.”