Orismilast is showing promise in atopic dermatitis (AD), according to topline results from the ADESOS study presented at the 2024 Revolutionizing Alopecia Areata, Vitiligo, and Eczema (RAVE) Conference in Chicago, IL.

This marks the first presentation of data from this study. Orismilast is a next-generation, high-potency PDE4 B/D selective inhibitor with reported positive results from a Phase 2b study in psoriasis and a Phase 2 study in hidradenitis suppurativa (HS). The U.S. Food and Drug Administration has cleared UNION’s Investigational New Drug (IND) application for orismilast and granted Fast Track designation for orismilast for the treatment of moderate to severe AD and moderate to severe HS.

Kim Kjøller, MD, Co-Chief Executive Officer of UNION Therapeutics, discussed the results of the ADESOS study and the company’s plans for Orismilast with The Dermatology Digest.

TDD: What is the main takeaway from  ADESOS?

Kim Kjøller, MD: “The ADESOS Phase 2b study confirms orismilast’s potential as a safe oral treatment for AD, with all active doses achieving statistical significance on the key efficacy measure of Investigator’s Global Assessment scale (IGA) 0/1, which will also be the primary endpoint for Phase 3. Orismilast also demonstrated a fast onset of itch reduction as measured by a ≥4-point reduction on the Numerical Rating (NRS) scale already at Week 2 for all dose arms. In line with other recent studies, a high placebo response was observed on the Eczema Area and Severity Index (EASI) scale driven by moderate patients, though also here the signal was clear when looking at severe patients (EASI>21) or harder-to-achieve endpoints (e.g., EASI-100), consistent with the overall findings as measured by IGA 0/1, patient-reported improvement of disease as well as a range of disease-related biomarkers, including thymus and activation-regulated chemokine (TARC)/CCL17. No new safety signals were identified in the study, confirming the well-established safety profile of the PDE4 class, and tolerability was also in line with the experience from the marketed PDE4 inhibitors; most frequent treatment-emergent adverse events (TEAEs) were gastrointestinal-related and headache, and generally mild and transient, typically occurring within the first weeks of treatment. The results in AD are consistent with late-stage clinical results generated in psoriasis and hidradenitis suppurativa, confirming orismilast’s potential as a safe oral treatment across a range of immunological indications. This builds on the well-established safety of the PDE4-class while being a next-generation compound yielding higher potency through selectivity for the B and D-subtypes of PDE4.”

TDD:  What is the next step research-wise?

Dr. Kjøller: “UNION has started preparations for Phase 3 studies for orismilast in AD, and an end-of-Phase 2 meeting has been scheduled with the FDA to discuss the orismilast development program for Phase 3 in AD. “

TDD: How is orismilast different than currently available AD therapies?

Dr. Kjøller:  “Orismilast is a next-generation PDE4-inhibitor that differentiates from earlier pan-PDE4 inhibitors through higher selectivity for the B/D subtypes of PDE4, that are considered the main drivers of inflammation, yielding a higher overall potency. This has been confirmed in late-stage clinical studies evaluating orismilast as a safe oral treatment for psoriasis and hidradenitis suppurativa, respectively.

Orismilast differentiates from biologics, injectable therapies, by being an oral treatment, which is the preferred route of administration for many patients. Additionally, orismilast has a fast effect on itch, separating from placebo in the first two weeks, while biologics generally have a slow itch relief. Most patients report that itch is the most bothersome symptom of their AD.

Orismilast differentiates itself from JAK inhibitors, the only oral therapies approved for the treatment of AD, by a favorable safety profile. JAKs all have a black box warning due to safety concerns with the drug class, and a large unmet medical need remains for safe oral treatments, which orismilast potentially can fulfill.“