Sanofi and Regeneron Pharmaceuticals drug Dupixent has won FDA approval for chronic spontaneous urticaria, introducing a new approach to the treatment of this inflammatory skin disorder. It’s the seventh FDA approved indication for the blockbuster product.
The regulatory decision announced Friday covers the treatment of patients age 12 and older whose chronic spontaneous urticaria (CSU) symptoms continue despite treatment with standard-of-care antihistamines.
CSU is partly driven by type 2 inflammation, a type of overactive immune response. This response lead to hives and itching; CSU is defined as disease that lasts for more than six weeks. Sanofi estimates 1.7 million people in the U.S. are affected by CSU. Despite the wide availability of antihistamines, the company says about half of CSU patients have disease that is inadequately controlled by these standard treatments.
Antihistamines target H1 receptors, receptors on immune cells that play a role in immune response and inflammation. The second-line treatment option for CSU is Genentech’s Xolair, an asthma drug that expanded its approval to the inflammatory skin disorder in 2014. Xolair is an antibody designed to block immunoglobulin E receptors, which are involved in allergic reactions and immune responses. But other pathways play a role in CSU. Dupixent, a drug administered by injection every two weeks, is a monoclonal antibody designed to block the signaling pathways IL-13 and IL-4.
Dupixent’s FDA approval in CSU is based on the results of two Phase 3 tests that evaluated the drug as an add-on to antihistamines, compared to a placebo and antihistamines. Results showed Dupixent met primary and secondary goals of reducing itch severity and itch and hive activity compared to the control arm at 24 weeks. The study drug arm also showed increased likelihood of well-controlled disease or a complete response at 24 weeks. On safety, the results were consistent with the known safety profile of Dupixent in its approved indications. The most common adverse event reported was injection site reactions.
Dupixent was first approved in 2017 as a treatment for atopic dermatitis. It’s Sanofi’s top-selling product, accounting for more than €13 billion (about $14.7 billion) in revenue in 2024. Sanofi’s inflammation and immunology strategy includes expanding use of the drug to other indications. Last year, the European Medicines Commission and the FDA approved Dupixent for chronic obstructive pulmonary disease.
“This FDA approval provides a new treatment option to help address the underlying drivers of these severe and recurring signs and symptoms,” Alyssa Johnsen, global therapeutic area head, immunology and oncology development at Sanofi, said in a prepared statement. “Dupixent has the potential to improve outcomes for CSU patients who previously had limited treatment options.”
In 2023, the FDA turned down Sanofi’s initial application for the drug in CSU, asking for more clinical data to show efficacy. That submission was based on two Phase 3 studies, one of which failed to meet the main trial goal. The resubmission included data from a third Phase 3 test. Dupixent is approved for CSU in Japan, the United Arab Emirates, and Brazil. The drug is still under review in this indication in Europe and other markets around the world.
There are other companies trying to bring new approaches to the treatment of CSU. Celldex Therapeutics is in late-stage clinical development with barzovolimab, an antibody drug designed to bind to the KIT receptor on mast cells. Evommune aims to address mast cell activation with an oral small molecule, EVO756. When the startup unveiled a $115 million Series C financing last October, it said it expected preliminary Phase 2b data in CSU in the first half of 2025.
But CSU drug research has also led to failures. In 2022, Third Harmonic discontinued development of an oral small molecule KIT inhibitor after Phase 1 data showed signs of potential liver toxicity. The company turned its focus to a different KIT-blocking small molecule, THB335, which is currently being readied for Phase 2 development. But last week, Third Harmonic announced plans to dissolve the company and sell its assets, including THB335, returning cash to shareholders.
Meanwhile, Allakos has twice fallen short in its effort to develop antibodies that inhibit mast cells. Last year, Allakos reported its drug lirentelimab did not beat a placebo in a Phase 2 test in CSU. The biotech turned its focus to a different drug, AK006. But the Phase 1 failure of that drug in January triggered the biotech’s second corporate restructuring in the past year.
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