ATS 2023 Updates: Dupixent – A Ray of Hope For Moderate To Severe Chronic Obstructive Pulmonary Disease (COPD)

• DUPIXENT has shown positive pivotal results for COPD, confirming the key role of IL-4 and IL-13 in type 2 inflammatory diseases.
• DUPIXENT has the potential to be the first biologic with unprecedented and paradigm-shifting clinical results to treat COPD, having demonstrated a statistically significant reduction in moderate to severe acute exacerbations of COPD, along with improvements in lung function
• DUPIXENT significantly improved quality of life, and reductions in the severity, with numerical improvements as early as 4 weeks after initiating treatment

Chronic obstructive pulmonary disease (COPD) is a life-threatening respiratory disease that damages the lung and causes airflow blockage, leading to progressive lung function decline. Long-term exposure to toxic particles and smoking are the key risk factors for developing COPD. Individuals often present with persistent cough and breathlessness that impair their ability to perform routine daily activities, besides leading to anxiety, depression, and sleep disturbances. 

As per Delveinsight’s analysis, in 2022, there were approximately 32 million diagnosed prevalent cases of COPD among the 7MM countries, with the US accounting for approximately 18 million cases.

As the third most common cause of death, it is a global health concern that is notoriously difficult to treat due to its heterogeneity. Patients have, for a long, been struggling with the debilitating symptoms of this progressive disease and there have been limited incremental improvements in current treatment options over the last decade. 

The current pharmacotherapy regime for COPD consists of maintenance and reliever medications (bronchodilators). Maintenance medications include inhaled corticosteroid (ICS), long-acting beta-agonist (LABA), tiotropium, or fixed-dose combinations of ICS and LABA or ipratropium and albuterol while reliever medications include short-acting beta-agonist (SABA), oral corticosteroids (OCS), nebulized ipratropium, and antibiotics. 

Due to recurrent acute exacerbations that require systemic corticosteroid treatment and may lead to hospitalization or even death, the cost of treatment is mostly high and increases with disease progression, leading to significant health and economic burden. 

There is a significant need for therapies that are disease-modifying and reduce exacerbations. While various therapies are being developed, Sanofi and Regeneron’s DUPIXENT (dupilumab) has become a frontrunner in the treatment of uncontrolled COPD with Type 2 inflammation. 

DUPIXENT, a fully human monoclonal antibody, is not an immunosuppressant. It inhibits the key central drivers of type 2 inflammation, the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways. 

At the recently held American Thoracic Society (ATS) International Conference 2023, Sanofi presented results from NCT03930732, Phase III BOREAS trial evaluating the use of dupilumab compared to placebo in adults currently on maximum SoC triple inhaled therapy. 

In this trial (the first of two Phase III trials), 939 adults of the age group 40 to 80 years, who were either current or former smokers, were randomized to receive DUPIXENT (n=468) or placebo (n=471), every two weeks, to their standard-of-care inhaled therapy, during the 52-week treatment period. The trial enrolled individuals who had moderate to severe disease with evidence of type 2 inflammation, measured by blood eosinophils levels ≥300 cells/μL. 

All primary and key secondary endpoints were met, with DUPIXENT demonstrating unprecedented and potentially paradigm-shifting clinical results, at a magnitude never seen before with a biologic. 

• There was a 30% reduction in the primary endpoint that evaluated the annualized rate of acute moderate or severe COPD exacerbations.  The annualized rate of moderate or severe exacerbations was 0.78 with dupilumab and 1.10 with placebo.
• There was also rapid and significant improvement in lung function from baseline with the benefit being sustained through 52 weeks. The prebronchodilator FEV₁ increased from baseline to week 12 by a least-squares mean of 160ml with dupilumab and 77ml with placebo.
• There were significant improvements in quality of life and respiratory symptoms, with the St. George’s Respiratory Questionnaire score improving by an LS mean of −9.7, and the Evaluating Respiratory Symptoms in COPD (E-RS–COPD) improving by an LS mean of −2.7 with dupilumab.
• The safety profile was in accordance with the known profile of DUPIXENT in its approved indications.  The overall rates of adverse events (AEs) were 77% for DUPIXENT and 76% for placebo, with the most commonly observed AEs being headache (8.1%), diarrhea (5.3%), and back pain (5.1%). AEs leading to deaths were well-adjusted between the two arms (1.7% placebo, 1.5% DUPIXENT).

While many investigational treatments have failed to demonstrate significant clinical outcomes leaving difficult-to-treat patients with limited treatment options, COPD caregivers can now breath a sigh of relief. 

“The findings of the BOREAS trial contribute to the growing form of evidence that supports as-needed anti-inflammatory therapy’s effectiveness in COPD. DUPIXENT has the potential to revolutionize the COPD treatment paradigm by lowering the risk of severe exacerbations in COPD patients, significantly improving respiratory symptoms. ”

Sanofi and Regeneron’s Dupixent is already churning up sales with considerable momentum across several indications and COPD will be another crowing stroke for the drug. The second, replicate Phase III trial of Dupixent in COPD (NOTUS) is ongoing with data anticipated by 2024, which will be followed by regulatory submission in the US and EU. COPD is a complex condition and considering GSK’s NUCALA and AstraZeneca’s FASENRA struggles with FDA approvals, DUPIXENT’s success will be exciting to watch. According to DelveInsights’ analysis, the COPD drug will have a moderate to fast uptake, attaining its peak share 6 years after launch in 2024.