Atopic dermatitis (AD) is a common inflammatory skin disease leading to flaky and itchy skin and is the most common skin disease in children, with 10% to 20% of children in developed countries affected. Although AD severity can vary from mild to severe, it is clear that this disease has a negative impact on the quality of life for all sufferers. This is due to the sometimes severe sleep deprivation caused by constant itching, as well as the physical and psychological impact of the disease and its treatment. However, children with AD will soon receive more effective treatment options, especially those with moderate to severe AD, as more developers begin expanding their investigations into this patient group.
AD is currently treated with proper skincare through the use of topical medicines such as emollients, topical calcineurin inhibitors, and topical corticosteroids. More recently, Opzelura (ruxolitinib), a topical Janus kinase (JAK) inhibitor, was FDA-approved for use in patients age 12 years and older, but its use is limited due to safety warnings. Systemic treatment is also often required to adequately control the disease for the treatment of moderate to severe patients. Therapies such as systemic corticosteroids, cyclosporin, and other immunomodulators have serious side effects, so their use is extremely limited in the paediatric group.
However, in June 2022, Sanofi and Regeneron announced that the FDA approved their interleukin (IL)-4/13 inhibitor, Dupixent (dupilumab), for the treatment of children ages six months to five years, with moderate to severe AD, whose disease is irresponsive to topical prescription therapies or when those therapies are not advisable. This is a huge step forward for the treatment of children with severe AD, as they require a more targeted approach to treatment, which would ultimately result in better long-term management and control of disease. Furthermore, Dupixent is widely known as the gold-standard therapy for the treatment of moderate to severe AD, so parents and caretakers may be less reluctant to initiate treatment as the safety profile of Dupixent is well established and favourable for patients in both the short and the long term.
In addition to Dupixent, there are other systemic agents being investigated for use in paediatric patients under 12 years, such as Olumiant (baricitinib), an oral JAK1/2 inhibitor; Rinvoq (upadacitinib), an oral JAK1 inhibitor; Adtralza/Adbry (tralokinumab), an anti-IL-13 biologic; and nemolizumab, an anti-IL-31 biologic. Eli Lilly’s Olumiant is being investigated in the Phase III trial BREEZE-AD-PEDS (NCT03952559), which is expected to be completed in May 2026, for use in children aged two to 17 years. It is already approved for use in adults across the 5EU (France, Germany, Italy, Spain and the UK) and Japan, but has yet to be approved in the US. AbbVie’s Rinvoq is being investigated in a Phase I trial (NCT03646604) for use in children aged two to 12 years, although this trial is not expected to read out until September 2024. Rinvoq has already been approved for use in adults and adolescents in the US and the EU, so the company has real-world evidence to support its clinical development program in a younger age group.
Leo Pharma’s Adtralza/Adbry is also being investigated in paediatric patients aged two to 11 years through the Phase II trial, TRAPEDS 1 (NCT05388760). TRAPEDS 1 is expected to read out in August 2024, but similarly to Rinvoq, it is also approved for use in adults in both the US and the EU. LEO is hoping to expand into adolescent patients, following a discussion at the Committee for Medicinal Products for Human Use (CHMP) agenda meeting on March 21–24 2022. This discussion was based on safety and efficacy data from the Phase III trial, ECZTRA 6 (NCT03526861). Galderma’s nemolizumab is being investigated in a Phase II trial (NCT04921345) for patients aged two to 12 years that is expected to read out in January 2025, but nemolizumab is only approved for use in adults in Japan, under the brand name Mitchga, so it falls behind its competitors in overall global access.
Currently, Dupixent is the only systemic treatment available for patients under 12 years of age, allowing Sanofi to secure a steep market advantage before competitors such as Eli Lilly, AbbVie, LEO Pharma, and Galderma can expand their agents into this patient population. However, the collective development programs provide hope for younger patients who are underserved within this market, especially those who have more severe AD, who are in need of an effective disease-modifying agent.