Dr. Ahmed The FDA has approved Dupixent for various allergic and eosinophilic conditions such as asthma and allergic rhinitis. It has also been proven to reduce exacerbations in patients with the eosinophilic variant of COPD.
Dupixent (Dupilumab) is a human monoclonal antibody that binds to IL4Rα which is shared by IL-4 and IL-13.
Thus, Dupilumab blocks the signaling pathways of both IL-4 and IL-13 which play an important role in the pathogenesis of asthma, atopic dermatitis, allergic rhinosinusitis, and other allergic conditions.
The current FDA approval of Dupixent is limited to the following conditions [Ref]:
- Eosinophilic Asthma
- Atopic Dermatitis
- Chronic Rhinosinusitis with Nasal polyposis
- Eosinophilic esophagitis
The role of Dupixent for COPD is being evaluated and two clinical trials have found Dupixent (Dupilumab) effective for COPD with type 2 inflammation.
| Read: |
These studies are discussed here:
Dupixent for COPD: Key points
- Chronic Obstructive Pulmonary Disease (COPD) is an extensive lung condition that makes it hard to breathe. It usually develops slowly over time and is often caused by smoking.
- The study involved almost 940 COPD patients with elevated blood eosinophil counts who still faced a risk of frequent exacerbations despite standard treatments.
- Earlier this year, the FDA granted Breakthrough Therapy designation for Dupixent as an add-on maintenance treatment in adult patients with uncontrolled COPD associated with a history of exacerbations and an eosinophilic phenotype thanks to the positive results from BOREAS. [ref]
- According to the BOREAS trial, a 30% decrease in moderate or severe acute COPD worsening over 52 weeks was associated with dupilumab.
Dupixent for COPD with Type 2 Inflammation:
Levels of inflammation in COPD are often categorized into type 1 and type 2.
Type 1 inflammation is a neutrophilic type that involves chronic bronchitis linked to persistent irritation and mucus production [ref].
Type 2 inflammation is associated with emphysema and involves inflammation that damages the air sacs in the lungs.
Some people with COPD may have a mix of both types.
Ongoing treatment for COPD aims to relieve symptoms and improve the quality of life. It often includes medications like bronchodilators to help open the airways and inhaled steroids to reduce inflammation.
However, only 1 out of 10 COPD patients adhere to the prescribed treatment regimen [ref].
Quitting smoking is crucial for managing COPD, and in more severe cases, oxygen therapy or surgery might be considered. Nevertheless, 30% to 50% of patients continue to smoke despite the clear benefits of cessation [ref].
A study from 2017 also showed that physicians faced a hurdle in counseling their patients against smoking [ref].
This worsening lung condition in COPD requires effective treatment. According to a study, people with COPD who had type 2 inflammation experienced fewer lung issues when they took dupilumab compared to those who took a fake treatment. [ref]
The ones on dupilumab had fewer serious flare-ups, improved breathing, better overall life quality, and milder breathing problems than those who only got a placebo.
| “It is being increasingly recognized that about 20-40% of patients with COPD have type 2 inflammation, and they are more likely to suffer from repeated exacerbations, and that is the reason why we are targeting patients with COPD with frequent exacerbations and type 2 inflammation with dupilumab” stated Surya Bhatt, MD, associate professor of medicine at the University of Alabama at Birmingham. [ref] |
Bhatt is a co-author of this study published in The New England Journal of Medicine.
| Read: |
Dupixent for COPD: Study trials and results:
The study tested a medicine called dupilumab in a phase 3 trial on 939 patients with COPD.
Despite using standard treatments, these patients had high levels of type 2 inflammation.
The BOREAS trial randomly assigned patients to receive either dupilumab or a fake treatment (placebo) every two weeks.
The main goal was to see how many moderate or severe COPD flare-ups happened each year.
Results showed that among the 468 patients who got dupilumab and the 471 who got placebo, those on dupilumab had significantly fewer flare-ups.
Breathing tests also improved more in the dupilumab group, with a sustained difference over 52 weeks.
Quality of life scores (SGRQ) and respiratory symptom scores (E-RS–COPD) were better with dupilumab at week 52.
Importantly, the number of side effects leading to stopping the treatment, serious side effects, and events causing death were similar in both groups.
“The high effect size of a 30% reduction in exacerbation frequency is remarkable,” Bhatt also said “Unlike other trials of biologics for COPD, dupilumab also resulted in a significant improvement in lung function and symptoms within 2 weeks of initiation, likely due to suppression of mucus production.” [ref]
| Read: |
Dupixent for COPD: The NOTUS trial
On 27th November, Regeneron Pharmaceuticals and Sanofi shared the news that the second phase of testing Dupixent for chronic obstructive pulmonary disease (COPD) significantly decreased flare-ups by 34%.
This confirms the positive outcomes seen in an earlier trial called BOREAS.
The new trial, called NOTUS, also found that using Dupixent improved lung function quickly within 12 weeks, and these benefits lasted for a year.
In the trial, researchers looked at how well Dupixent works compared to a fake treatment (placebo) in adults with COPD.
The trial included patients already using the maximum inhaled therapy (triple therapy) and still had uncontrolled symptoms of eosinophilic COPD with blood eosinophils ≥300 cells per μL.
The results, which are from a preliminary analysis, were so positive in improving the study’s main goal that they will be considered the main analysis.
Regeneron and Sanofi plan to share the data from this trial and the positive results from the BOREAS trial with the U.S. Food and Drug Administration (FDA) by the end of the year.
George D. Yancopoulos, M.D., Ph.D., Board Co-Chair, President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent, stated,
| “We are highly encouraged by these remarkable results from NOTUS showing a 34% reduction in COPD exacerbations compared to placebo, confirming the unprecedented results from our first Phase 3 trial, BOREAS.” “These results demonstrate the important role of type 2 inflammation in yet another chronic and debilitating disease, and the ability of Dupixent to address this inflammation. We are working to submit these data rapidly to the FDA,” George further added. |
| Read: |
In conclusion:
Dupixent is a novel approach to treating a subtype of COPD that has a predominant allergic component.
These patients have symptoms similar to asthma and COPD and usually have high blood or sputum eosinophilia.
Until now most treatment regimens of COPD patients included one or more of the following treatments:
- Anticholinergics
- Bronchodilators
- Inhaled corticosteroids, and
- Phosphodiesterase inhibitors
The approval of Dupixent for COPD signifies a milestone as it may represent the inaugural instance of a first-in-class therapeutic approach for treating patients afflicted with COPD displaying an eosinophilic variant.
The current treatment and medications approved for COPD other than Dupixent are summarized in the table below [Ref]:
Anticholinergic Inhalers for COPD: | Brand Name |
| Aclidinium | Tudorza Pressair |
| Glycopyrronium | Seebri Neohaler |
| Ipratropium | Atrovent |
| Tiotropium | Spiriva |
| Umeclidinium | Incruse Ellipta |
| Revefenacin | Yupelri |
Beta-agonist Inhalers for COPD: | Brand Name |
| Arformoterol | Brovana |
| Formoterol | Foradil; Perforomist |
| Indacaterol | Arcapta Neohaler |
| Salmeterol | Serevent |
| Olodaterol | Striverdi Respimat |
Inhaled Corticosteroids for COPD: | Brand Name |
| Beclomethasone | Qvar |
| Fluticasone | Flovent |
| Ciclesonide | Alvesco |
| Mometasone | Asmanex |
| Budesonide | Pulmicort |
| Flunisolide | Aerobid |
Combination Inhaled Medicines for COPD: | Brand Names |
| Albuterol and ipratropium | Combivent Respimat; Duoneb |
| Budesonide and formoterol | Symbicort |
| Fluticasone and salmeterol | Advair |
| Fluticasone and vilanterol | Breo Ellipta |
| Formoterol and mometasone | Dulera |
| Tiotropium and olodaterol | Stiolto Respimat |
| Umeclidinium and vilanterol | Anoro Ellipta |
| Glycopyrrolate and formoterol | Bevespi Aerosphere |
| Indacaterol and glycopyrrolate | Utibron Neohaler |
| Fluticasone umeclidinium and vilanterol | Trelegy Ellipta |
| Budesonide glycopyrrolate and formoterol | Breztri Aerosphere |
Phosphodiesterase Inhibitor for COPD: | Brand Name |
| Roflumilast | Daliresp |
Antibiotics for COPD: | Brand Name |
| Azithromycin | Azomax |
| Read: |
