On 7 June, Sanofi and Regeneron announced that the US Food and Drug Administration (FDA) had approved their interleukin (IL)-4/13 inhibitor, Dupixent (dupilumab) for the treatment of children aged six months to five years with moderate-to-severe atopic dermatitis (AD) whose disease is irresponsive to topical prescription therapies or when those therapies are not advisable. Dupixent is now the first and only biologic medicine approved to treat moderate-to-severe AD from infancy through adulthood.
The FDA approval was based on positive efficacy and safety data from the Phase III Liberty AD PRESCHOOL (NCT03346434) trial evaluating Dupixent 200mg or 300mg (weight-based) given every four weeks plus low-potency topical corticosteroids (TCS) compared against TCS alone. The primary endpoint of Investigator Global Assessment (IGA) of 0 (clear) or 1 (almost clear skin) was met by 28% of patients in the Dupixent group and 4% of patients for placebo. The co-primary endpoint of Eczema Area and Severity Index (EASI-75) from baseline was met by 53% of patients treated with Dupixent versus 11% for placebo.
A clinically meaningful and significant reduction in itch was achieved by 48% of patients treated with Dupixent compared with 9% given placebo. This data reinforces Dupixent’s standing as a gold-standard therapy for the treatment of moderate-to-severe AD; moreover, young children with severe AD are a significantly underserved population of patients, thus giving Sanofi and Regeneron a chance to capitalise on the significant gap in the market.
Dupixent had already been approved for use in adult (≥18 years) and adolescent (≥12 years) patients in March 2017 and March 2019 in the US, respectively, and subsequently for the treatment of severe AD in pediatric patients (six to 11 years of age) in May 2020. This highlights the IL-4/13 inhibitor’s broad label across different patient groups, which continues to bolster confidence in the agent as the companies also tout real-world evidence to support messaging of Dupixent’s strong safety and efficacy profile across a range of patient groups.
Although Dupixent is a widely adopted therapy for the treatment of AD, there are other companies seeking to expand into the paediatric population to garner market share from Dupixent. These include, notably, AbbVie’s Janus kinase (JAK)-1 inhibitor, Rinvoq (upadacitinib)—approved in the US for adults and adolescents in January this year; Pfizer’s JAK-1 inhibitor Cibinqo (abrocitinib)—approved in the US for adults in January this year; Eli Lilly’s JAK-1/2 inhibitor, Olumiant (baricitinib)—awaiting FDA approval following filing in April last year; Leo Pharma’s marketed anti-IL-13 Adtralza/Adbry (tralokinumab)—approved in the US for adult patients in December last year; and Galderma’s anti-IL-31 Phase III pipeline candidate, nemolizumab.
With AbbVie having initiated a Phase I (NCT03646604) safety and tolerability study investigating Rinvoq in patients aged two to 12 years, it is expected that part of AbbVie’s lifecycle management strategy for Rinvoq includes expansion to a younger patient population. Interim data on the safety profile of the JAK inhibitor in this patient population will be key for uptake and physician opinion of the therapy. Leo Pharma is also investigating Adbry/Adtralza in the 2–11 age group in a Phase II trial, TRAPEDS 1 (NCT05388760); the trial currently has an estimated primary completion date of August 2024, so there will be a long wait before interim safety and efficacy data is published.
Unlike Rinvoq and Adtralza, Olumiant is undergoing Phase III development for paediatric AD, in the BREEZE-AD PEDS (NCT03952559) study, which is enrolling both adolescents and paediatrics (aged 2–17 years). Eli Lilly is strategically targeting both populations in an effort to compete with Dupixent’s broad label and wide patient reach, in a move that could also allow Eli Lilly to compete more fiercely with fellow JAK inhibitors Rinvoq and Cibinqo.
In order to fiercely compete with Dupixent, developers—particularly those with JAK inhibitors—will need to conduct extensive safety studies similar to the open-label Dupixent study, LIBERTY AD PED-OLE (NCT02612454), conducted by Sanofi and Regeneron. GlobalData anticipates Eli Lilly’s Olumiant to launch for paediatric patients (2–11 years) in 2024, with Galderma’s nemolizumab to follow closely behind in 2026. As such, Sanofi and Regeneron will have 2–3 years to monopolise the six months to 11 years moderate-to-severe group, which GlobalData estimates to be 11.9 million diagnosed prevalent cases across the seven major markets (7MM: the US, France, Germany, Italy, Spain, UK and Japan) in 2022. In terms of commercial value, GlobalData estimates sales from the paediatric AD population (aged zero to 11 years) to reach $1.6bn across the 7MM, growing at a compound annual growth rate (CAGR) of 7.3%. This further exemplifies the gap and potential within this segment of the AD market.
Sanofi and Regeneron’s Dupixent is anticipated to reach sales of $5.3bn in the US by 2030, growing at a CAGR of 6.3%, while the US AD market is expected to grow at a CAGR of 10.5%, so it is clear that Dupixent is responsible for a huge proportion of growth in that market, further showcasing its blockbuster potential in a lucrative market. Other agents such as Rinvoq, Olumiant, Adtralza and Cibinqo are expected to see some growth, with US peak sales of around $1.8bn, $380.4m, $1.1bn and $476.0m respectively. It should be noted that their growth will be overshadowed by Dupixent as more and more age groups are exposed to the IL-4/13 inhibitor, although there are some patients who do not respond well to the biologic, leaving room for second-line therapy with these agents.
Dupixent is the only biologic currently available for patients under 12 years of age, allowing Sanofi to secure a steep market advantage before competitors such as Leo Pharma, Pfizer, Eli Lilly and Galderma can expand their agents into this patient population. This FDA approval has solidified first-mover advantage for Dupixent and reinforces its market-leading position for the treatment of moderate-to-severe AD, providing hope for younger patients who are underserved within this market. GlobalData anticipates strong uptake of Dupixent in this patient population due to the pent-up demand for an effective disease-modifying agent.