Dupixent aces second COPD study, setting up FDA filing

With a second positive phase 3 trial in hand, Sanofi and Regeneron have said they plan to file for approval of Dupixent in chronic obstructive pulmonary disease (COPD), a potentially huge market for the drug.

The results of the NOTUS trial showed the IL-4 and IL-13 inhibitor Dupixent (dupilumab) met its primary endpoint with “overwhelming efficacy”, said the two drugmakers, reducing the acute exacerbations that afflict people with the progressive disease by 34% compared to placebo when added to standard therapy.

The results – in patients with moderate-to-severe COPD with high levels of blood eosinophils, a marker for type 2 inflammation – reinforce the results of the BOREAS trial reported earlier this year, which had an identical protocol and was used to file for approval in Europe.

Now, with two supporting phase 3 trials, the way is cleared to file for regulatory approval in the US and other world markets, with an FDA filing due before year-end. The regulator has already awarded breakthrough status for Dupixent as a COPD therapy, which will accelerate the review process.

Analysts at Evercore ISI predicted that Dupixent could make $3.5 billion in sales from COPD alone, driving peak sales upwards of $20 billion a year towards the end of this decade. The drug is already a mega-blockbuster, bringing in €7.75 billion ($8.5 million) in the first nine months of this year from current indications like atopic dermatitis and severe asthma.

COPD is the third leading cause of death worldwide, and affects an estimated 12.5 million people in the US, leading to 150,000 deaths, according to 2020 data, although those numbers are likely underestimated as COPD is still underdiagnosed and underreported.

The disease is also one of the most expensive chronic conditions, generating healthcare costs of over $30 billion per year in the US. Much of that cost is driven by exacerbations, the sudden and life-threatening deterioration in lung function experienced by COPD patients.

Not all patients with COPD have type 2 inflammation – studies suggest up to a third have persistent blood eosinophils at levels that indicate this is present – but the sheer number of patients worldwide make it a major new opportunity for Sanofi and Regeneron.

NOTUS has backed up the strong data seen in BOREAS, with the reduction in exacerbations accompanied by “rapid and significant” improvements in lung function by 12 weeks that were sustained at 52 weeks, said Sanofi and Regeneron.

Specifically, the drug improved lung function from baseline by 139 mL at 12 weeks compared to 57 mL for placebo, with the difference at week 52 115 mL for Dupixent and 54 mL for placebo.

Regeneron’s R&D chief George Yancopoulos said the results are “unprecedented” in COPD, and position Dupixent to become the first biological therapy for the illness.

“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,” he added.

Sanofi and Regeneron’s COPD pipeline also includes itepekimab, an antibody that binds to and inhibits IL-33 that has already shown preliminary signs of activity in a phase 2a proof-of-concept study in COPD. It has activity across both type 1 and type 2 inflammation and has already been fast-tracked by the FDA.

Itepekimab is in two phase 3 COPD studies – AERIFY-1 and AERIFY-2 – that are due to report results concurrently in 2025, according to the clinicaltrials.gov database.