AAD: Will Sanofi and Regeneron’s Dupixent be a game-changer or just another antibody on the COPD scrapheap?

Despite chronic obstructive pulmonary disease (COPD) being the world’s third most fatal disorder, treatment advances have been limited over the last decade.

That could change soon however as Sanofi and Regeneron are investigating Dupixent’s ability to tame the inflammatory disease.

A phase 3 trial is set to read out in the first half of this year, which could pave the way for an approval.

In awaiting the data there is both anticipation and apprehension. A long-awaited biologic option cold be a game changer in the treatment of COPD. But other antibodies—such as AstraZeneca’s Fasenra and GSK’s Nucala—have failed in COPD.

Is there something about Dupixent’s dual action—targeting IL-4 and IL-13 proteins as opposed to Fasenra and Nucala which target IL-5 proteins—that can make a difference?

Ahead of the American Academy of Dermatology meeting in New Orleans, Paul Rowe, M.D., Sanofi’s VP, head of global medical for immunology, explained that COPD is irreversible as current inhaled treatments provide only symptomatic relief when inflammation occurs. Sanofi's hope with Dupixent is that the drug can limit the bronchial spasms, which cause the inflammation.

“Dupixent has an effect on blocking the action of those cytokines,” Rowe said in an interview. “By blocking those cytokines we’re able to potentially also impact the inflammation and hence, have a chance at impacting those irreversible causes.”

In 2019, Sanofi's antibody partner Regeneron expressed doubts about Dupixent’s ability to make a difference in COPD, considering the effort a longshot.

“We wouldn’t rank this as something we have a high degree of confidence in,” CEO Len Schleifer said at the time.

But in 2020, the company said Dupixent met an early efficacy threshold in its phase 3 trial, warranting continuation of the study. The company did not reveal that threshold, however.

Rowe described the “viscous spiral” of COPD, where sufferers have dyspnea (breathlessness) and begin to modify their daily activities, which brings on more dyspnea.  

“They don’t necessarily seek their physician. And then they continue to spiral to the point where they can’t even walk their dog,” Rowe said. “The hope is that we can somehow impact that downward spiral.”

Originally approved in 2017 for eczema, soon to be followed by a nod to treat asthma, Dupixent has added FDA endorsements for three more inflammatory conditions, earning the distinction as a “pipeline in a drug.” It rang up sales of $8.7 billion last year, which was a 40% increase from 2021 and is projected by Evaluate Pharma’s consensus to reach $18 billion in sales in 2028.

COPD is mostly caused by smoking, which carries a “stigma,” Rowe said, contributing to the lack of progress made in advancing new treatments.

Last year, a study by Phreesia Life Sciences showed that COPD patients were reluctant to discuss their symptoms with a physician and 34% said they didn’t fully understand their condition.