Dupixent® (dupilumab) Demonstrates Significant Reduction in Itch and Hives in Phase 3 Trial for Chronic Spontaneous Urticaria

News on February 26, 2022 /BioValleyBIOON/ -- Sanofi and its partner Regeneron recently presented at the 2022 American Academy of Allergy,AsthmaAndImmunologyPositive results from the pivotal Study A of the LIBERTY-CUPID clinical program (NCT04180488), a Phase 3 randomized, double-blind, placebo-controlled trial evaluating Dupixent (Chinese trade name: 达必妥, generic name: dupilumab) for the treatment of moderate-to-severe chronic spontaneous urticaria (CSU), were announced at the annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI).

Data show,In biologic-naive patients with moderate-to-severe CSU, treatment with Dupixent plus antihistamine for 24 weeks significantly reduced itching and hives compared to antihistamine alone, nearly halving the itch and hive activity scores.

CSU is a chronic inflammatory skin condition characterized by the sudden appearance of hives and/or deep swelling of the skin. Despite standard care treatments, patients with CSU often experience persistent symptoms such as itching or burning sensations, which can be debilitating and significantly impact quality of life. Swelling typically occurs on the face, hands, and feet, but can also affect the throat and upper airways. CSU is commonly treated with antihistamines; however, in patients with limited treatment options, up to 50% of cases remain uncontrolled.

CSU is a complex chronic disease. This timeMeetingThe data published reinforce the potential of targeting and blocking IL-4 and IL-13 in the treatment of CSU. These two cytokines are key drivers of type 2 inflammation.

Professor Marcus Maurer from the Charité University Medical Center in Berlin, Germany, stated: "Despite the use of standard antihistamines, many patients with Chronic Spontaneous Urticaria (CSU) continue to struggle with severe itching, burning, and pain associated with hives and subcutaneous swelling, which can significantly disrupt their daily lives. These encouraging results suggest that in patients who have not achieved disease control with antihistamines alone, adding Dupixent leads to improved signs and symptoms and better disease control."

LIBERTY-CUPID is a Phase 3 randomized, double-blind, placebo-controlled clinical program. Study A was conducted in 138 patients aged ≥6 years with moderate-to-severe CSU who remained symptomatic despite treatment with non-sedating H1 antihistamines and had not previously received omalizumab. In the study, patients were randomly assigned to two treatment groups: (1) Dupixent group receiving Dupixent (injection, subcutaneous) + non-sedating H1 antihistamine (tablet, oral) for 24 weeks; (2) Placebo group receiving matched placebo (injection, subcutaneous) + non-sedating H1 antihistamine (tablet, oral) for 24 weeks. The primary endpoints of the study were: change from baseline in itch at Week 24 (measured by the weekly Itch Severity Score [ISS7]) and change from baseline in itch and urticaria at Week 24 (measured by the weekly Urticaria Activity Score [UAS7]).

The topline results published in July 2021 showed that Study A achieved the primary endpoint and all key secondary endpoints at 24 weeks of treatment. Data presented at the 2022 AAAAI Annual Meeting indicated:Compared to the patient group receiving placebo and standard care therapy with antihistamines, the Dupixent + antihistamine combination therapy group experienced nearly a twofold reduction in itching and urticaria activity, with continuous improvement until week 24.The specific data are as follows:

-- After 24 weeks of treatment, according to the 0-21 point pruritus severity scale measurement results (Dupixent group pruritus severity decreased by 10.24 points, placebo group pruritus severity decreased by 6.01 points, p<0.001), Dupixent group pruritus severity decreased by 63%, placebo group pruritus severity decreased by 35%. This is the primary endpoint in the United States (secondary endpoint in the EU).

-- After 24 weeks of treatment, according to the measurement results of the 0-42 point Urticaria Activity Scale (Dupixent group decreased by 20.53 points, placebo group decreased by 12.00 points, p<0.001), the severity of urticaria activity (itching and hives) in the Dupixent group decreased by 65%, while the placebo group decreased by 37%. This is the primary endpoint in the EU (secondary endpoint in the US).

——The safety results of Dupixent are consistent with the known safety profile in its approved dermatological indications. During the 24-week treatment period, the overall incidence of adverse events was similar between the Dupixent group and the placebo group (50% in the Dupixent group vs. 59% in the placebo group). The most common adverse event was injection site reactions (11% in the Dupixent group vs. 13% in the placebo group).

LIBERTY-CUPID Project Study B was conducted in adult and adolescent patients with moderate to severe CSU who were receiving standard-of-care treatment but remained symptomatic and were intolerant or had an inadequate response to omalizumab. Based on a pre-specified interim analysis conducted in February 2022, the study was determined to be futile and will be stopped. Although there was a positive numerical trend observed in the reduction of itch and hives, the interim analysis results showed no statistical significance for the primary endpoint. Currently, the potential use of Dupixent in CSU is still under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.

Mechanism of Action of Dupixent (Image Source: dupixenthcp.com)

Dupixent targets the key drivers of type 2 inflammation. It is a fully human monoclonal antibody that specifically inhibits the overactive signaling of two key proteins, IL-4 and IL-13. IL-4/IL-13 are two cytokines that are considered to be key drivers of intrinsic inflammation in allergic diseases and other type 2 inflammatory diseases, including atopic dermatitis.Asthma, Eosinophilic Esophagitis, Grass Allergy, Peanut Allergy, etc.

Dupixent was launched at the end of March 2017 and has currently been approved to treat three diseases caused by type 2 inflammation: moderate to severe atopic dermatitis (patients ≥6 years old), moderate to severeAsthma(≥6 years old patients), chronic rhinosinusitis with nasal polyps (CRSwNP, adult patients).

In China, in June 2020, Dupixent (Dupilumab) was approved by the National Medical Products Administration (NMPA) for the treatment of adult patients with moderate-to-severe atopic dermatitis (AD). Dupixent is the world’s first and only targeted biologic therapy approved for treating adult patients with moderate-to-severe atopic dermatitis, addressing an unmet clinical need in China. It delivers rapid, significant, and sustained improvement in skin lesions and pruritus symptoms in atopic dermatitis patients. Thanks to the regulatory reform, Dupixent received approval in China two years ahead of schedule, offering Chinese patients a new treatment option.

Currently, Sanofi and Regeneron are also conducting an extensive clinical program to evaluate Dupixent for the treatment of diseases caused by allergies and other type 2 inflammations, including: chronic obstructive pulmonary disease (Phase 3), pediatric atopic dermatitis (6 months to 5 years, Phase 3), eosinophilic esophagitis (Phase 3), bullous pemphigoid (Phase 3), prurigo nodularis (Phase 3), chronic spontaneous urticaria (Phase 3), chronic inducible urticaria (Phase 3), chronic rhinosinusitis without nasal polyps (Phase 3), allergic fungal rhinosinusitis (Phase 3), allergic bronchopulmonary aspergillosis (Phase 3), and peanut allergy (Phase 2). (Bioon.com)

Source of the original text:Late-breaking Phase 3 Data at 2022 AAAAI Annual Meeting Show Dupixent® (dupilumab) Significantly Reduced Itch and Hives in Patients with Chronic Spontaneous Urticaria