Sanofi, Regeneron Suffer Rare Dupixent Flop in CSU

Even a little rain must fall on the good fortune of Regeneron and Sanofi‘s blockbuster anti-inflammatory drug Dupixent. After roaring into February with positive data in five different indications, the two companies announced a late-stage trial had been halted due to futility.

The Phase III CUPID Study B was halted early after an interim analysis indicated the trial would not reach statistical significance despite what the companies said were numeric improvements observed across key endpoints. The CUPID B study assessed Dupixent (dupilumab) in patients with chronic spontaneous urticaria (CSU), a chronic inflammatory skin disease characterized by the sudden onset of hives on the skin.

Despite the setback in CSU, the two companies said they are committed to advancing Dupixent in this indication, particularly since previous Phase III data in biologic-naïve patients showed Dupixent significantly reduced itch and hives compared to standard-of-care antihistamines alone.

Dupixent is an inhibitor of interleukin-4 (IL-4) and interleukin-13 (IL-13), key drivers in type 2 inflammation prevalent in multiple disease indications, including asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), atopic dermatitis and eosinophilic esophagitis.

The CUPID B study assessed Dupixent and antihistamines in CSU patients who are refractory to Genentech’s Xolair (omalizumab), which is currently the only FDA-approved treatment for CSU when antihistamines are not enough. Regeneron and Sanofi said trial data showed positive numerical trends in reducing itch and hives but did not meet statistical significance following an interim analysis conducted by an independent monitoring committee.

The two companies intend to share the Phase III CUPID B study results at an upcoming scientific forum. Data from the Phase III LIBERTY study will be presented at the American Academy of Allergy, Asthma and Immunology Annual Meeting later this month.

Regeneron and Sanofi said they are determining the next steps forward in this program.

“Chronic spontaneous urticaria is a very complex disease, and these data add to the body of evidence assessing the underlying drivers of disease burden, including the potential role of interleukin-4 and interleukin-13,” George D. Yancopoulos, M.D., Ph.D., president and chief scientific officer at Regeneron, said in a statement. “While Dupixent did not show a significant benefit in the most difficult-to-treat patients who remain refractory to all approved medicines, we are carefully assessing the potential role of Dupixent in CSU based on the success of the first Phase III trial in biologic-naïve patients, where Dupixent nearly doubled the reduction in itch and urticaria activity.”

Dupixent has been a significant revenue driver for Sanofi and Regeneron. Sanofi earned about $4.2 billion from Dupixent sales in 2021 and Regeneron earned about $1.8 billion from the sales.