The atopic dermatitis (AD) space boasts an impressive pipeline of 80 agents, which is indicative of the spotlight this therapy area is receiving. Figure 1 summarises all pipeline products currently in Phase I, II and III stages of clinical development for AD within the seven major markets (7MM), namely the US, the five major European markets (5EU: France, Germany, Italy, Spain and the UK) and Japan.
The pipeline includes 80 agents in varying stages of clinical development. Of these, 35% (28 agents) are in Phase I trials, 55% (44 agents) in Phase II trials, and 10% (8 agents) in Phase III trials. Biologics comprise 36% of these agents (29 agents), while 64% are small molecules (51 agents).
There is an array of targets within the biologic group, including various interleukin (IL) inhibiting biologics. Key late-stage IL inhibitors include AbbVie’s risankizumab (anti-IL-23), Galderma’s nemolizumab (anti-IL-31), Eli Lilly’s lebrikizumab (anti-IL-13) and Janssen’s bermekimab (anti-IL-1). These agents are following in the footsteps of Sanofi/Regeneron’s Dupixent (dupilumab), a first-in-class IL-4/IL-13 dual inhibitor approved for the treatment of moderate-to-severe AD since 2019. With global reported sales of over $4.0bn last year, Dupixent has seen strong uptake in AD, signalling the market’s readiness for other IL inhibitors.
Another notable class among the pipeline biologics are anti-OX40 targeting agents. Among these agents, Kyowa Kirin/Amgen’s KHK-4083 is ready for assessment in a Phase III study, while Kymab’s KY-1005 and Ichnos Sciences’ telazorlimab are still completing Phase II trials. The anti-OX40 class uses a completely novel mechanism of action, and early data suggests it could disrupt the AD treatment paradigm. All biologics in development for AD are administered subcutaneously. Although injections may not be preferred by some, they can be an attractive option for patients because they are administered less frequently (every one to four weeks), which could increase compliance.
There are also several small-molecule agents in the early and late-stage pipeline for AD. Numerous Janus kinase (JAK) inhibitors and phosphodiesterase-4 (PDE4) inhibitors are in later stages of development, as well as a few from novel classes such as the sphingosine 1-phosphate receptor (S1PR) modulators.
JAK inhibitors provide a more convenient option for patients who prefer topical or oral agents for treatment. There are currently ten JAK inhibitors in varying stages of clinical development for AD, six of which are topical agents and four of which are orally administered. Key late-stage JAK inhibitors include three oral agents, AbbVie’s Rinvoq (upadacitinib), Pfizer’s abrocitinib and Asana Bioscience’s gusacitinib, as well as two topical agents, namely Incyte’s ruxolitinib and Pfizer’s brepocitinib. While the majority of JAK inhibitors in late-stage development are targeting moderate-to-severe patients, ruxolitinib and brepocitinib are being positioned for patients with mild-to-moderate AD.
The potential availability of a new mechanism of action for patients with milder forms of the disease could have a strong impact on AD market dynamics. In AD, PDE4 inhibitors are only being developed for topical use. Some notable late-stage products are Otsuka Pharmaceutical/Medimetriks’ difamilast and Arcutis Biotherapeutics’ roflumilast. These agents will not be the first topical PDE4 inhibitors to enter the AD market but are set to follow Pfizer’s Eucrisa (crisaborole), a widely used topical PDE4 inhibitor for mild-to-moderate AD. Whether they are targeting JAKs or PDE4, the topical route of administration is clearly a huge focus for investigators involved in AD clinical development.
Another interesting class in development for AD are the S1PR modulators. Although S1PR agents are a minority in the pipeline, they have the potential to offer a unique treatment option for patients. Arena Pharmaceuticals’ etrasimod is a progressive new oral therapy within this class that is ready for Phase III, with a pivotal study program expected to begin in the second half of this year. There are no S1PR modulators on the market for AD, so etrasimod would be a first-in-class agent if it is brought to market. While S1PR modulators will need to compete with the rapidly growing JAK inhibitor class, safety may end up being a key differentiator for these agents.
GlobalData’s analysis of the AD pipeline suggests there are numerous promising agents in development for various age groups and severities. It is expected this intense clinical activity will lead the treatment landscape for AD to completely transform over the next decade.