Dupixent approved in Singapore as the first-ever biologic medicine for patients with COPD

Following recent approvals in the EU, US and China, the Singapore approval is based on two replicate phase 3 studies that showed Dupixent achieved significant reduction in exacerbations, and also showed improvements in lung function and health-related quality of life compared to placebo.

The Health Sciences Authority (HSA) has approved Dupixent (dupilumab) for adults as an add-on maintenance treatment for uncontrolled chronic obstructive pulmonary disease (COPD) characterized by raised blood eosinophils who are on a stable combination of an inhaled corticosteroid (ICS), a long-acting beta2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA), or on a combination of a LABA and a LAMA if ICS is not appropriate.

Dupilumab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement.

In Singapore, Dupixent is the first biologic medicine approved to treat these COPD patients. The prevalence of COPD is estimated to be around 6% of the general population[1], and it ranks as a leading cause of death[2].

Weeling Quek
Head of Immunology at Sanofi, Southeast Asia & India
"With the Singapore approval of Dupixent for COPD, we are not just launching a new indication; we are igniting a beacon of hope for countless individuals. This milestone underscores our commitment towards patients battling this debilitating disease. We are dedicated to transforming the lives of patients, giving them the chance to reclaim precious moments with their loved ones, and experience a life with fewer limitations."   

The FDA approval is based on data from two phase 3 studies (BOREAS and NOTUS) that evaluated the efficacy and safety of Dupixent compared to placebo in adults currently on maximal standard-of-care inhaled therapy (nearly all on triple therapy) with inadequately controlled COPD and blood eosinophils ≥300 cells per μL. Patients who received Dupixent in BOREAS (n=468) and NOTUS (n=470) experienced the following outcomes, 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.

Rapid improvements in post-bronchodilator FEV1 from baseline at week 12 compared to placebo, sustained at 52 weeks. Statistically significant improvements of similar magnitude were observed in pre-bronchodilator FEV1 from baseline at 12 and 52 weeks, a key secondary endpoint.

51% response in a health-related quality of life measure in both trials compared to 43% and 47% with placebo at 52 weeks, as assessed by a 4-point improvement on the St. George's Respiratory Questionnaire (SGRQ).

Safety results in both studies were generally consistent with the known safety profile of Dupixent in its approved indications. In pooled BOREAS and NOTUS data, the most common adverse events (>2%) more frequently observed in patients on Dupixent compared to placebo were viral infection, headache, nasopharyngitis, back pain, diarrhea, arthralgia, urinary tract infection, local administration reaction, rhinitis, eosinophilia, toothache and gastritis. While less common, cholecystitis was reported in 0.6% of patients on Dupixent compared to 0.1% of patients on placebo.

About COPD

COPD is a respiratory disease that damages the lungs and causes progressive lung function decline and is the fourth leading cause of death worldwide. Symptoms include persistent cough, excessive mucus production and shortness of breath that may impair the ability to perform routine daily activities, which may lead to sleep disturbances, anxiety, and depression. COPD is also associated with a significant health and economic burden due to recurrent acute exacerbations that require systemic corticosteroid medicine and/or antibiotics. Smoking and exposure to noxious particles are key risk factors for COPD, but even individuals who quit smoking can still have progressive lung disease.

About half of COPD patients continue to experience exacerbations despite being on triple inhaled therapy. In the US, approximately 300,000 people live with inadequately controlled COPD and an eosinophilic phenotype. Patients with an eosinophilic phenotype contribute to an ~30% increase in exacerbations and an increased risk of COPD-related re-hospitalizations within a year.

About the Dupixent COPD phase 3 study program

BOREAS and NOTUS were replicate, randomized, phase 3, double-blind, placebo-controlled studies that evaluated the efficacy and safety of Dupixent in adults who were current or former smokers with moderate-to-severe COPD with an eosinophilic phenotype, as defined by blood eosinophils ≥300 cells per µL. The studies included adults with COPD across a broad range of clinical presentations, including those with chronic bronchitis and emphysema. The studies enrolled 1,874 patients who were aged 40 to 80 years in BOREAS and 40 to 85 years in NOTUS.

During the 52-week treatment period, patients in BOREAS and NOTUS received Dupixent or placebo every two weeks added to a maximal standard-of-care inhaled triple therapy of ICS, LABA and LAMA. Double maintenance therapy, which included LABA and LAMA, was allowed if ICS was not appropriate.

The primary endpoint for BOREAS and NOTUS evaluated the annualized rate of acute moderate or severe COPD exacerbations. 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, and safety.

The results of both BOREAS and NOTUS were separately published in The New England Journal of Medicine.

About Sanofi and Regeneron's COPD Clinical Research Program

Sanofi and Regeneron are motivated to transform the treatment paradigm of COPD by examining the role different types of inflammation play in the disease progression through the clinical assessment of two biologics, Dupixent and itepekimab. Dupixent is a first-in-class biologic that inhibits the signaling of the interleukin-4 (IL4) and interleukin-13 (IL13) 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 (IL33), an initiator and amplifier of broad inflammation in COPD. 

Itepekimab is currently under clinical investigation for COPD in two phase 3 studies and its safety and efficacy have not been evaluated by any regulatory authority. 

About Dupixent

Dupixent is a fully human monoclonal antibody that inhibits the signaling of the IL4 and IL13 pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in phase 3 studies, establishing that IL4 and IL13 are two of the key and central drivers of type 2 inflammation that play a major role in multiple related and often co-morbid diseases.

Dupixent has received regulatory approvals in more than 60 countries in one or more indications including certain patients with atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, chronic spontaneous urticaria, and COPD in different age populations. More than 1,000,000 patients are being treated with Dupixent globally.

Dupilumab Development Program

Dupilumab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical studies involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.

In addition to the currently approved indications, Sanofi and Regeneron are studying dupilumab in a broad range of diseases driven in part by type 2 inflammation or other allergic processes in phase 3 studies, including chronic pruritus of unknown origin and bullous pemphigoid. These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority.

About Sanofi
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Sources:

Year-to-year trajectories of hospital utilisation rates among patients with COPD: a real-world, single-centre, retrospective cohort study - PMC

Principal Causes of Death