FDA Approves Dupilumab as First Biologic Treatment for COPD

The FDA approved dupilumab (Dupixent; Regeneron/Sanofi) today for treating patients with uncontrolled chronic obstructive pulmonary disease (COPD) and an eosinophilic phenotype.¹

This approval makes dupilumab the first biologic treatment for COPD. It is a human monoclonal antibody that inhibits the signaling of IL-4 and IL-13 pathways, central drivers of the type 2 inflammation underlying COPD and related conditions, like asthma and atopic dermatitis; it is administered via subcutaneous injection. Dupilumab was previously approved to treat patients with moderate to severe atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and prurigo nodularis.

“This latest approval represents an important next chapter for Dupixent, giving those with COPD a novel option that has demonstrated the unprecedented ability to help patients experience fewer exacerbations, while also helping them breathe better and improve quality of life in Phase 3 trials,” George D. Yancopoulos, MD, PhD, principal inventor of dupilumab and board cochair, president, and chief scientific officer at Regeneron, said in a statement.

This approval was based on results from the phase 3 BOREAS (NCT03930732) and NOTUS (NCT04456673) trials, which demonstrated that dupilumab can significantly reduce COPD exacerbations.² The first trial was BOREAS, which evaluated the safety and efficacy of dupilumab in 939 adults aged 40 to 80 with moderate to severe COPD; all participants were current or former smokers.³ 

In this trial, dupilumab met the primary end point by reducing moderate or severe acute COPD exacerbations at 52 weeks (P = .0005; 30% reduction). It also demonstrated dupilumab’s ability to significantly improve lung function at 12 weeks compared to placebo (P < .0001; 60 mL vs 77 mL, respectively); its benefits lasted up to week 52 (P = .0003).

“BOREAS opened up a completely new understanding of presentations in terms of inflammation of COPD,” Klaus Rabe, MD, PhD, one of the study’s investigators, said in an interview with The American Journal of Managed Care^® at the European Respiratory Society Congress.⁴ “...Since it [type 2 inflammation] does play a role, it’s amenable to change with something that addresses type 2 inflammation through, for example, a monoclonal antibody, something like Dupixent.”

Next, the NOTUS trial, a replicate trial to BOREAS, evaluated the efficacy and safety of dupilumab for 935 patients aged 40 to 85 years with uncontrollable COPD and type 2 inflammation taking the maximal standard-of-care inhaled therapy (triple therapy)⁵; like the BOREAS trial, these patients were current or former smokers.

It met its primary end point, confirming the results of the BOREAS trial and demonstrating that dupilumab significantly reduced COPD exacerbations by 34% compared to the placebo arm. However, 67% of those in the experimental arm and 66% of the placebo arm had adverse events (AEs); the most common AEs were diarrhea, back pain, and headache.²

The European Medicines Agency approved dupilumab as an add-on treatment for patients with COPD in July 2024,¹ and it was also approved earlier today in China.⁶

“People living with inadequately controlled COPD have long awaited new medicines to help manage the daily suffering they experience from breathlessness, coughing, wheezing, exhaustion, and unpredictable hospitalization,” Jean Wright, MD, chief executive officer of the COPD Foundation, said.¹ “...We welcome the approval of this new therapeutic option to offer patients a new way to help gain better control of their disease.”

References

1. Dupixent approved in the US as the first-ever biologic medicine for patients with COPD. September 27, 2024. Accessed September 27, 2024. https://www.globenewswire.com/en/news-release/2024/09/27/2954551/0/en/Press-Release-Dupixent-approved-in-the-US-as-the-first-ever-biologic-medicine-for-patients-with-COPD.html
2. Hunter E. Data from phase 3 trials demonstrate efficacy of dupilumab for treating COPD, type 2 inflammation. December 4, 2023. Accessed September 26, 2023. https://www.ajmc.com/view/data-from-phase-3-trials-demonstrate-efficacy-of-dupilumab-for-treating-copd-type-2-inflammation
3. Dupixent (dupilumab) late-breaking phase 3 COPD results presented at ATS and simultaneously published in the New England Journal of Medicine. May 21, 2023. Accessed September 26, 2024. https://www.sanofi.com/en/media-room/press-releases/2023/2023-05-21-18-17-12-2672904
4. Steinzor P. BOREAS trial: new findings on type 2 inflammation in COPD. September 10, 2024. Accessed September 26, 2024. https://www.ajmc.com/view/boreas-trial-new-findings-on-type-2-inflammation-in-copd
5. Dupixent significantly reduced COPD exacerbations in second positive phase 3 trial, accelerating FDA submission and confirming potential to become first approved biologic for this serious disease. Sanofi. November 27, 2023. Accessed September 26, 2024. https://www.sanofi.com/en/media-room/press-releases/2023/2023-11-27-06-30-00-2785836
6. Dupixent approved in China as the first-ever biologic medicine for patients with chronic obstructive pulmonary disease (COPD). September 27, 2024. Accessed September 27, 2024. https://www.globenewswire.com/news-release/2024/09/27/2954417/0/en/Dupixent-dupilumab-Approved-in-China-as-the-First-ever-Biologic-Medicine-for-Patients-with-Chronic-Obstructive-Pulmonary-Disease-COPD.html