FDA Approves Dupilumab for Adolescents and Adults With H1 Antihistamine-Refractory Chronic Spontaneous Urticaria

Today, the US FDA approved dupilumab (Dupixent; Regeneron and Sanofi) for the treatment of chronic spontaneous urticaria (CSU) in patients aged 12 years and older who have not previously reached controlled disease status with H1 antihistamine treatment.¹

The approval marks the introduction of the first targeted therapy for CSU in more than a decade.

“[Dupilumab] is the first new targeted treatment for chronic spontaneous urticaria, or CSU, in over 10 years, with pivotal trials demonstrating its ability to help patients significantly reduce the hallmark symptoms of intense itch and unpredictable hives associated with this disease," said George D. Yancopoulos, MD, PhD, board co-chair, president, and chief scientific officer at Regeneron. "With this FDA decision, [dupilumab] is now approved for 7 chronic, debilitating atopic conditions driven in part by underlying type 2 inflammation, several of which have been shown to co-morbidly occur with CSU, such as atopic dermatitis and asthma – providing patients with one treatment that might help multiple atopy conditions. We look forward to bringing [dupilumab] to the more than 300,000 CSU patients in the US with inadequately controlled disease on standard-of-care treatment who, until now, had limited treatment options.”

Image Credit: © Tada Images - stock.adobe.com

A Long-Awaited Advancement in CSU Care

Dupilumab, an interleukin-4 (IL-4) and interleukin-13 (IL-13) inhibitor, has already been approved for multiple type 2 inflammatory conditions, including atopic dermatitis, asthma, eosinophilic esophagitis, and prurigo nodularis.

The approval comes after years of research and regulatory engagement. In October 2023, the FDA issued a complete response letter for the initial supplemental Biologics License Application (sBLA),² stating that additional efficacy data were needed to support approval. However, the agency did not identify concerns regarding dupilumab’s safety or manufacturing process.

In response to the CRL, Regeneron and Sanofi resubmitted the sBLA, which was accepted by the FDA in November 2024.³ That resubmission included updated efficacy and safety data from a third phase 3 trial, LIBERTY-CUPID Study C, in biologic-naïve patients with CSU uncontrolled by antihistamines.

LIBERTY-CUPID: Building the Case for Approval

The LIBERTY-CUPID (NCT04180488) clinical development program, which supported the approval, consisted of 3 randomized, double-blind, placebo-controlled phase 3 trials.⁴

• Study A and Study C: Conducted in biologic-naïve CSU patients whose symptoms remained uncontrolled despite H1 antihistamine therapy.
• Study B: Conducted in patients who were not only uncontrolled on H1 antihistamines but also refractory or intolerant to omalizumab (Xolair; Novartis).

Across the trials, patients receiving dupilumab experienced significant improvements in CSU symptoms. In Study C, which provided the pivotal data for approval, nearly half of participants achieved well-controlled disease status, marked by meaningful reductions in itch severity and hives, compared with placebo. These findings aligned with earlier results seen in Study A, reinforcing the drug’s efficacy.

Adverse events observed during the studies were consistent with dupilumab’s known safety profile. The most common adverse effects included injection site reactions and COVID-19 infections, which occurred in both treatment and placebo groups. No new safety signals were identified.

Filling a Decade-Long Gap in CSU Treatment

Prior to today’s approval, patients with CSU who did not respond to H1 antihistamines had limited treatment options, most notably omalizumab, an anti-IgE monoclonal antibody.

Dupilumab’s approval fills this gap as the first new targeted therapy for CSU in more than 10 years, and the only approved biologic that inhibits IL-4 and IL-13 signaling, key drivers of type 2 inflammation.

"It’s been 10 years with no innovation for chronic urticaria… now to switch gears for a new approval that the dermatology specialists are familiar with… ultimately, the patients benefit," said Jason Hawkes, MD, MS, a board-certified dermatologist and co-owner, chief scientific officer, and investigator at the Oregon Medical Research Center in Portland, Oregon, in a recent interview with Dermatology Times ahead of the approval.

Watch the full interview here.

"Most of these patients—around 50%—don’t respond to antihistamines, even at high-doses," Hawkes added.

Industry Response and Expert Insights

The companies are expected to launch Dupixent for CSU in the near future.

"It's going to bring patients into a specialty dermatology that hasn't really been managing these patients. We're going to pick up new observations, new insights," Hawkes said. "Dermatology specialists are familiar and comfortable with this therapy. They use it for other indications, but now they have a familiar therapy for a disease that they know how to recognize but weren't historically treating. I think [dupilumab] comes into that landscape where they
have the comfort with the therapy that's had a very good safety record having, in some indications, approval down to even 6 months of age."

References

1. Dupixent® (dupilumab) approved in the US as the first new targeted therapy in over a decade for chronic spontaneous urticaria (CSU). News release. Globe Newswire. April 18, 2025. Accessed April 18, 2025. https://www.globenewswire.com/news-release/2025/04/18/3064133/0/en/Dupixent-dupilumab-Approved-in-the-U-S-as-the-First-New-Targeted-Therapy-in-Over-a-Decade-for-Chronic-Spontaneous-Urticaria-CSU.html
2. Regeneron and Sanofi provide update on Dupixent (dupilumab) SBLA for chronic spontaneous urticaria. News release. Regeneron Pharmaceuticals Inc. October 20, 2023. Accessed April 18, 2025. https://investor.regeneron.com/news-releases/news-release-details/regeneron-and-sanofi-provide-update-dupixentr-dupilumab-sbla
3. Dupixent (dupilumab) sBLA accepted for FDA review for the treatment of chronic spontaneous urticaria (CSU). News release. Regeneron. November 15, 2024. Accessed April 18, 2025. https://investor.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-sbla-accepted-fda-review-treatment-chronic
4. Dupilumab for the treatment of chronic spontaneous urticaria in patients who remain symptomatic despite the use of H1 antihistamine and who are naïve to, intolerant of, or incomplete responders to omalizumab (LIBERTY-CSU CUPID). ClinicalTrials.gov ID NCT04180488. Last updated December 11, 2024. Accessed April 18, 2025. https://clinicaltrials.gov/ct2/show/NCT04180488