Regeneron, Sanofi Receive CRL for Add-On Dupilumab sBLA for Chronic Spontaneous Urticaria


The latest indication for the dual inflammatory pathway-targeting biologic expands dupilumab's clinical availability to third chronic skin disease.

FDA Approves Add-On Dupilumab for Chronic Spontaneous Urticaria

The US Food and Drug Administration (FDA) has provided a Complete Response Letter (CRL) to the supplemental Biologics License Application (sBLA) for dupilumab (Dupixent) as a treatment for patients with chronic spontaneous urticaria (CSU).1

According to Sanofi and Regeneron, the CRL stated the FDA requires additional efficacy data to support a potential approval to treat CSU. The companies stated an ongoing clinical trial is continuing to enroll patients and is anticipated to provide the relevant efficacy data requested by the FDA.

"Regeneron and Sanofi remain committed to working with the FDA to advance the study of Dupixent for patients living with CSU who are inadequately controlled by antihistamines," the companies' statement read. "The potential use of Dupixent in CSU is currently under clinical development, and the safety and efficacy have not been fully evaluated by any regulatory authority."

CSU is historically uncontrolled in approximately half of all diagnosed patients, with the primary treatment option being antihistamines. With the inflammation-targeting biologic that is dupilumab, the add-on therapy was associated with significantly improved disease management status in treated patients.

The companies' application was supported by findings from the LIBERTY-CSU CUPID study program, including a phase 3, randomized, controlled, 24-week trial assessing the efficacy and safety of add-on dupilumab versus placebo in patients ≥6 years old with symptomatic CSU despite treatment with antihistamines. The trial showed that at week 24, mean Itch Severity Score over 7 days (ISS7) and Urticaria Activity Score over 7 days (UAS7) improved significantly among dupilumab treated patients versus baseline (P = .0005 and P = .0003, respectively).2

Investigators, led by Marcus Maurer, MD, of Charite-Universitatsmedizin Berlin in Germany, additionally observed comparable safety per treatment-emergent adverse events (TEAEs) between the treatment arms; 35 (50%) patients receiving dupilumab experienced a TEAE, with the most common being injection site reactions (n = 8 [11.4%]).

In further CUPID analyses presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2023 Annual Meeting in San Antonio this March, Maurer and colleagues additionally reported that dupilumab was associated with a significantly greater change from baseline in mean Dermatology Life Quality Index (DLQI) scores versus placebo at 24 weeks (-10.8 vs -7.6; P = .0026).3

A separate component of the phase 3 CUPID trial program sought to assess dupilumab’s efficacy and safety as an add-on therapy to antihistamines versus omalizumab in patients with CSU; Regeneron and Sanofi announced the trial had been stopped due to futility of statistically-significant outcomes in February 2022.4

Another trial, a case series presented later that year, found that patients who discontinued omalizumab for their CSU were more likely to achieve disease resolution—per UAS7 scores of 0 through 14 – 22 months—when treated with dupilumab.5

“Evidence of benefit lasting long after discontinuation of this therapy suggests that discontinuation of dupilumab can be safe and cost efficient and effective therapy that accomplishes clinical resolution in many patients while limiting unnecessary exposure and costs of requiring maintenance, biologic, and other therapies,” investigators wrote at the time.


  2. Maurer M, Casale T, Saini S, Laws E, et al. Dupilumab Significantly Reduces Itch and Hives in Patients With Chronic Spontaneous Urticaria: Results From a Phase 3 Trial (LIBERTY-CSU CUPID Study A). The Journal of Allergy and Clinical Immunology. Vol. 149, Iss. 2, Supp. Published February 2022.
  3. Smith T. Improvement in Chronic Spontaneous Urticaria Activity and Quality of Life with Dupilumab. HCPLive. Published online March 3, 2023.
  4. Butera A. Phase 3 Trial on Dupilumab for Chronic Spontaneous Urticaria Stopped. HCPLive. Published online February 18, 2022.
  5. Smith T. Dupilumab Intervention After Omalizumab Discontinuation May Resolve Chronic Spontaneous Urticaria. HCPLive. Published online November 15, 2022.

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