Dupilumab (DUPIXENT), a Monoclonal Antibody for COPD

In September 2024 the Food and Drug Administration approved dupilumab (DUPIXENT) as an add-on maintenance treatment for adults with inadequately controlled eosinophilic chronic obstructive pulmonary disease (COPD). The drug has also been approved for certain patients with other diseases, including asthma, eosinophilic esophagitis, and chronic rhinosinusitis with nasal polyps.[1],[2]

Initially approved in 2017 for the treatment of atopic dermatitis, dupilumab is a monoclonal antibody available as a 300-milligram (mg) single-dose prefilled pen or syringe. For COPD, the drug is injected subcutaneously (under the skin) every other week.

Eosinophilic COPD is so named because it involves an inflammatory response caused by eosinophils, a type of white blood cell that helps the body fight infections and allergens. Dupilumab should be used only for patients with eosinophilic COPD for whom other treatments have failed to adequately control flare-ups. About 20-30% of patients with COPD have elevated levels of eosinophils in their blood.[3]

What is COPD?

COPD is a chronic lung condition characterized by damaged and inflamed lungs or airways that can block (or obstruct) the flow of air.[4] Patients with COPD often find it difficult to breathe freely. Other common symptoms include chest tightness, coughing up mucus, and wheezing.

In the United States, COPD affects about 14 million adults; the illness leads to disability and death.[5] The most common cause of COPD is the long-term use of cigarettes. However, COPD can also be caused by long-term exposure to air pollution, secondhand smoke, and workplace exposure to fumes, dust or chemicals.

Although there is no cure for COPD, quitting smoking and other disease management can help to prevent further damage to the lungs.[6] Inhaled medications can help to improve breathing by widening airways, such as bronchodilators, or reducing inflammation, such as glucocorticoids.

When COPD progresses, patients are at higher risk of heart disease and lung cancer.[7] Patients can also experience flare-ups, called exacerbations, during which symptoms are worse for a few days or weeks. During such flare-ups patients struggle more than usual with their breathing, coughing more often, or coughing up more mucus, which can also disrupt sleep.[8]

The efficacy and safety of dupilumab

For some people with COPD, flare-ups may be linked to an increased amount of eosinophils in the blood.[9] These cells activate two proteins that can cause inflammation; dupilumab blocks the actions of these proteins. Importantly, dupilumab is an add-on maintenance treatment; it is not a replacement for inhaled medications to address sudden breathing problems.

The supplemental approval of dupilumab for COPD was based on two double-blind trials that included current and former smokers with eosinophilic COPD and uncontrolled flare-ups despite receiving the maximum standard-of-care treatment of two bronchodilators and a glucocorticoid. The subjects were randomized to receive either a subcutaneous injection of dupilumab or a placebo in addition to their standard-of-care treatments.[10],[11]

The main outcome measured in both trials was the rate of moderate or severe flare-ups during the 52-week period of the trials. The trials also assessed improvements in lung function (as measured in the amount of air exhaled after taking a full breath) and health-related quality of life.

In the first trial, which included 939 subjects, the rate of moderate or severe flare-ups per patient per year was significantly lower for subjects in the dupilumab group (0.78) than for subjects in the placebo group (1.10).[12] As compared with the placebo group, lung function also modestly improved for dupilumab-treated subjects, and health-related quality of life was slightly better.[13]

The rate of adverse events was comparable in subjects treated with the drug (77.4%) and those who received placebo (76.0%).[14] The rate of serious adverse events (13.6%), including those resulting in death (1.5%), in the dupilumab group was slightly lower than in the placebo group (15.5% and 1.7%, respectively). Major cardiovascular events occurred less often in the dupilumab group (0.9%) than in the placebo group (1.9%).

The second trial included 935 subjects.[15] Similar to the first trial, the rate of moderate or severe flare-ups for subjects treated with dupilumab (0.86) was significantly lower than for those in the placebo group (1.30). There were modest improvements in lung function in the dupilumab group as compared with the placebo group but no significant differences in quality of life.[16] The rate of any or serious adverse events were again comparable in both groups, but more adverse events resulted in death in the drug group (2.6%) than in the placebo group (1.5%).[17] Similar to the first trial, subjects in the dupilumab group also had fewer major cardiovascular events (0.6%) than those in the placebo group (1.5%).

In patients with eosinophilic COPD, the most common adverse events associated with dupilumab include viral infections, headaches, common colds, back and joint pain, diarrhea, and urinary tract infections.[18] The prescribing information also warns that there is an increased risk of allergic reactions (including anaphylaxis), conjunctivitis (pink eye) and keratitis (inflammation of the cornea) with the use of dupilumab.

Both trials had limitations, and some patient groups were not well-represented.[19],[20] For example, only about 1% of the subjects were Black, people with asthma were excluded, and only about 30% of the subjects were current smokers.

What You Can Do

If you have COPD and are a smoker, stopping smoking is the most important step to improve your health. Stopping smoking can slow down the progression of COPD and can help prevent complications such as lung cancer and heart disease. If your symptoms worsen, talk to your clinician about different treatment options. Also, identify and avoid triggers for your flare-ups, which can include smoking, mold, perfume or pollen.[21] Regular vaccinations for flu, pneumonia and COVID-19 are also important.

Only consider dupilumab if you have eosinophilic COPD and other treatments have failed to adequately control flare-ups. If you are already taking dupilumab, do not reduce or stop taking other COPD treatments such as bronchodilators or inhaled glucocorticoids.
 

References

[1] Regeneron. Label: dupilumab (DUPIXENT). September 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761055s064lbl.pdf. Accessed November 19, 2024.

[2] Nature. News in brief. FDA approves first monoclonal antibody for COPD. October 1, 2024. https://www.nature.com/articles/d41573-024-00164-7. Accessed November 26, 2024.

[3] Maniscalco M, Candia C, Ambrosino P, et al. Chronic obstructive pulmonary disease's eosinophilic phenotype: clinical characteristics, biomarkers and biotherapy. Eur J Intern Med. 2024:S0953-6205(24)00435-7.

[4] Mayo Clinic. COPD. Overview. August 30, 2024. https://www.mayoclinic.org/diseases-conditions/copd/symptoms-causes/syc-20353679. Accessed November 26, 2024.

[5] Liu Y, Carlson SA, Watson KB, et al. Trends in the prevalence of chronic obstructive pulmonary disease among adults aged ≥18 years — United States, 2011–2021. MMWR Morb Mortal Wkly Rep 2023;72:1250–1256.

[6] Mayo Clinic. COPD. Overview. August 30, 2024. https://www.mayoclinic.org/diseases-conditions/copd/symptoms-causes/syc-20353679. Accessed November 26, 2024.

[7] Mayo Clinic. COPD. Overview. August 30, 2024. https://www.mayoclinic.org/diseases-conditions/copd/symptoms-causes/syc-20353679. Accessed November 26, 2024.

[8] StatNews. Regeneron, Sanofi blockbuster dupixent wins FDA approval for COPD. September 27, 2024. https://www.statnews.com/2024/09/27/regeneron-sanofi-blockbuster-dupixent-wins-fda-approval-for-copd/. Accessed November 26, 2024.

[9] Regeneron. Label: dupilumab (DUPIXENT). September 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761055s064lbl.pdf. Accessed November 26, 2024.

[10] Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med. 2023 Jul 20;389(3):205-214.

[11] Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation. N Engl J Med. 2024;390(24):2274-2283.

[12] Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med. 2023 Jul 20;389(3):205-214.

[13] King Han, M and Dransfield, M. Management of refractory chronic obstructive pulmonary disease. UpToDate. Updated October 18, 2024.

[14] Ibid.

[15] Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation. N Engl J Med. 2024;390(24):2274-2283.

[16] King Han, M and Dransfield, M. Management of refractory chronic obstructive pulmonary disease. UpToDate. Updated October 18, 2024.

[17] Ibid.

[18] Regeneron. Label: dupilumab (DUPIXENT). September 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761055s064lbl.pdf. Accessed November 26, 2024.

[19] Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with type 2 inflammation indicated by eosinophil counts. N Engl J Med. 2023 Jul 20;389(3):205-214.

[20] Bhatt SP, Rabe KF, Hanania NA, et al. Dupilumab for COPD with blood eosinophil evidence of type 2 inflammation. N Engl J Med. 2024;390(24):2274-2283.

[21] King Han, M and Dransfield, M. Management of refractory chronic obstructive pulmonary disease. UpToDate. Updated October 18, 2024.