Dupixent® Phase 3 COPD Study Data Presented at ATS and Published in NEJM

Late-breaking data from the NOTUS phase 3 study on Dupixent® (dupilumab) were presented at the 2024 American Thoracic Society (ATS) International Conference. This data, concurrently published in the New England Journal of Medicine, showcased Dupixent's potential as an add-on maintenance treatment for adults with uncontrolled chronic obstructive pulmonary disease (COPD) who are on maximal standard-of-care inhaled therapy and exhibit type 2 inflammation. The study confirmed the promising results previously demonstrated in the phase 3 BOREAS study.

Dr. Surya Bhatt from the University of Alabama at Birmingham, one of the study's co-principal investigators, highlighted that in his over 20 years of experience, advancements for COPD have been limited. The NOTUS study revealed that Dupixent reduced exacerbations to an unprecedented degree in phase 3 COPD clinical research. This suggests that Dupixent, if approved, could offer a groundbreaking new treatment for the COPD community.

The primary and key secondary objectives of the NOTUS study were achieved. All participants were on maximal standard-of-care inhaled therapy, with most on triple therapy. The study involved 470 patients receiving Dupixent and 465 on placebo. Key findings include a 34% reduction in moderate or severe COPD exacerbations over 52 weeks for those on Dupixent compared to placebo. Additionally, patients on Dupixent showed more than double the improvement in lung function (pre-bronchodilator FEV1) at both 12 and 52 weeks. There were also numerically greater improvements in health-related quality of life and reductions in respiratory symptom severity over 52 weeks.

The safety profile of Dupixent was generally consistent with its known safety data across its approved uses. Adverse events (AEs) were comparable between the Dupixent and placebo groups, with specific AEs like COVID-19, nasopharyngitis, and headache being slightly more common in the Dupixent group. On the contrary, COPD-related AEs were more frequent in the placebo group. The rate of deaths due to AEs was slightly higher in the Dupixent group (2.6%) compared to placebo (1.5%).

Dupixent is under Priority Review by the US Food and Drug Administration (FDA) for this potential new use, with a target decision date of June 27, 2024. Regulatory reviews are also ongoing in the European Union and China, among other regions. It's important to note that Dupixent's safety and efficacy for COPD have not yet been fully evaluated by any regulatory authority.

COPD is a progressive respiratory disease that leads to declining lung function, characterized by symptoms like persistent cough, breathlessness, and excessive mucus production. It significantly impacts daily activities and can cause anxiety, depression, and sleep issues. The disease also poses a considerable health and economic burden due to frequent acute exacerbations requiring systemic corticosteroids or hospitalization. While smoking and exposure to harmful particles are primary risk factors, even non-smokers or former smokers can develop COPD. In the US, around 300,000 people suffer from uncontrolled COPD with type 2 inflammation, and no new treatments have been approved for over a decade.

The Dupixent COPD phase 3 study program includes the BOREAS and NOTUS studies, which are randomized, double-blind, placebo-controlled trials evaluating Dupixent's efficacy and safety in adult smokers or former smokers with moderate-to-severe COPD and type 2 inflammation. These studies excluded individuals with asthma. Over the 52-week treatment period, patients received bi-weekly doses of Dupixent or placebo, in addition to maximal standard-of-care inhaled therapy.

Sanofi and Regeneron, the companies behind Dupixent, are also investigating another biologic, itepekimab, which targets the interleukin-33 (IL-33) pathway, another potential inflammation driver in COPD. This compound is currently in phase 3 trials.

Dupixent is already approved in over 60 countries for various indications, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, prurigo nodularis, and chronic spontaneous urticaria. The extensive Dupixent development program has involved over 10,000 patients across 60 clinical studies, underscoring its significant therapeutic potential in type 2 inflammation-driven diseases.