Dupixent Achieves Primary and Secondary Endpoints in Pivotal Phase 3 Trial for Moderate-to-Severe Atopic Dermatitis in Infants and Young Children Aged 6 Months to 5 Years

On August 30, 2021, Sanofi and Regeneron announced that dupilumab injection (dupilumab, marketed as Dupixent), co-developed by the two companies, met the primary endpoint and all secondary endpoints in a pivotal Phase 3 clinical trial for the treatment of children aged 6 months to 5 years with moderate-to-severe atopic dermatitis (AD). The data showed that at Week 16, compared to standard treatment, adding dupilumab to topical corticosteroids (TCS) significantly reduced overall disease severity and significantly improved patients' skin clearance rates, itch, and health-related quality of life measures.

Dupilumab is a fully human monoclonal antibody that inhibits signaling through the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways. IL-4 and IL-13 are key and central drivers of type 2 chronic inflammation, including atopic dermatitis (AD), asthma, and chronic rhinosinusitis. In 2016, the U.S. FDA granted Breakthrough Therapy designation to this drug for the treatment of severe atopic dermatitis in children aged 6 months to 11 years. Notably, in June of this year, the drug also received Priority Review designation from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for a new indication: the treatment of moderate-to-severe AD in adults and children aged 6 to less than 12 years whose disease is inadequately controlled with topical prescription therapies or when such therapies are not recommended.

The primary endpoints in this Phase 3 trial were the proportion of patients achieving complete or almost complete clearance of skin symptoms (IGA score of 0 or 1) and the proportion achieving a 75% improvement in the Eczema Area and Severity Index (EASI-75). The pre-specified primary analysis demonstrated that at Week 16, 28% of subjects in the dupilumab group achieved clear or almost clear skin compared with the placebo group (4%, p≤0.0001), which was more than seven times the rate observed in patients receiving TCS monotherapy. Additionally, compared with the placebo group (11%), 53% of patients in the dupilumab group achieved EASI-75 (p≤0.0001), representing a 70% reduction in overall disease severity and a 49% reduction in pruritus.

In the trial, the drug demonstrated a safety profile consistent with its known safety profile for the treatment of atopic dermatitis. During the 16-week treatment period, the overall incidence of adverse events (AEs) was 64% in the dupilumab + TCS group compared with 74% in the placebo group. The most common AEs and AEs of special interest included nasopharyngitis, upper respiratory tract infection, conjunctivitis, herpes virus infections, and injection site reactions.

AD is a chronic type 2 inflammatory disease, with 85%–90% of patients experiencing disease onset before 5 years of age. The debilitating symptoms in infants and young children with moderate-to-severe AD often persist into adulthood, including intense, persistent pruritus and skin lesions that may cover large areas of the body. These lesions result in dry, cracked, erythematous or hyperpigmented, crusted, and oozing or bleeding skin, and increase the risk of cutaneous infections. The symptoms negatively impact patients' emotional well-being, sleep patterns, and quality of life. Furthermore, AD may predispose individuals to the development of other atopic diseases, such as asthma.

References:

[1] Dupixent® (dupilumab) pivotal trial meets all primary and secondary endpoints becoming first biologic medicine to significantly reduce signs and symptoms of moderate-to-severe atopic dermatitis in children as young as 6 months. Retrieved August 30, 2021, from https://www.sanofi.com/en/media-room/press-releases/2021/2021-08-30-07-00-00-2288011

(Original text omitted)

▽Follow 【WuXi AppTecVirtue】WeChat Official Account