Atopic Dermatitis Pipeline: What to Watch

GlobalData expects the atopic dermatitis (AD) pipeline will experience a transformation in the next 10 years because 64% of the pipeline consists of small molecular agents, like Janus kinase (JAK) inhibitors and phosphodiesterase-4 (PDE4) inhibitors, while the rest of the pipeline is biologics.1 There are also other novel drug classes in development such as sphingosine 1-phosphate receptor (S1PR) modulators and OX40 inhibitors.

“The AD space has seen a dramatic rise in interest from the pharmaceutical industry, which is exemplified by the sheer size of its clinical development pipeline. An increasing number of companies are seeing the potential in this indication for its return on investment and are entering the space singularly or through strategic partnerships. The introduction of unique drug classes to the AD space will provide patients with a plethora of options and will give doctors more choice although this may come with further scrutiny especially for the JAK class,” said Ramla Salad, pharma analyst at GlobalData, London, England.

The breakdown of current clinical trials includes 35% of pipeline agents in phase 1 trials, 55% in phase 2, and 10% in phase 3. 

Salad notes that of the JAK inhibitors, 3 are oral agents: upadacitinib (Rinvoq; AbbVie), abrocitinib (PF-04965842; Pfizer), and gusacitinib (ASN002; Asana Bioscience). While 2 are topical agents: ruxolitinib cream and brepocitinib (PF-06700841; Pfizer). 

The PDE4 inhibitors to watch, according to Salad, are difamilast (OPA 15406; Otsuka Pharmaceutical/Medimetriks) and roflumilast (ARQ-151; Arcutis Biotherapeutic) which are developed for topical use only in AD.

While many JAK inhibits that are in late-stage development are intended to treat patients with moderate to severe AD, ruxolitinib cream and brepocitinib target mild to moderate disease and have the potential to affect AD market dynamics, according to GlobalData.

“Difamilast and roflumilast are set to follow Pfizer’s Eucrisa (crisaborole), a widely used topical PDE4 inhibitor for mild to moderate AD. The topical route of administration is clearly a huge focus for investigators involved in AD clinical development,” Salad said.

Biologics, which make up 36% of the pipeline, contain multiple interleukin (IL) inhibitors such as: risankizumab (Skyrizi; AbbVie) which targets IL-23, nemolizumab (CD14152; Galderma) which targets IL-31, lebrikizumab (ILY3650150; Eli Lilly) which targets IL-13, and bermekimab (JNJ-77474462; Janssen) which targets IL-1. These bring variety and diversity to the AD treatment space. According to Salad, these IL inhibitors are looking to repeat the success of dupilumab (Dupixent; Sanofi/Regeneron) that have been approved since 2019 and seen great profits in 2020.

Other pipeline research to look for is the biologic OX40 inhibitors and small molecule S1PR modulators.

“Among the OX40 agents, Kyowa Kirin/Amgen’s KHK-4083 is ready for phase 3 assessment, while Kymab’s KY-1005 and Ichnos Sciences’ telazorlimab are still completing phase 2 trials. The anti-OX40 class uses a completely novel mechanism of action, and early data suggests it could disrupt the AD treatment paradigm,” said Salad.

There is currently no S1PR modulators on the market for AD, but etrasimod (APD334; Arena Pharmaceuticals) an oral S1PR therapy is ready for a phase 3 trial. Many will be watching to see what the safety results are from this trial as it may be the key differentiator between the many biologic treatment options.

Reference:

1. Atopic dermatitis boasts a large and transformative pipeline, says GlobalData. GlobalData. Published July 28, 2021. Accessed August 2, 2021. https://globaldata.com/atopic-dermatitis-boasts-large-transformative-pipeline-says-globaldata/