UNION Therapeutics' Phase 2b Study Confirms Orismilast's Potential as Safe, Effective Oral Treatment for Atopic Dermatitis

UNION Therapeutics A/S, a privately held pharmaceutical development company based in Hellerup, Denmark, has announced promising results from its Phase 2b ADESOS study for orismilast in adults with moderate to severe atopic dermatitis (AD). The findings were presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024 by Prof. Dr. Eric Simpson.

The study evaluated the efficacy and safety of three doses of orismilast (20mg, 30mg, and 40mg) against placebo over 16 weeks. A total of 233 patients participated in the trial. The primary endpoint was the Investigator Global Assessment (IGA) score of 0/1 at Week 16. The results were significant, with 26.3%, 24.3%, and 30.9% of patients in the 20mg, 30mg, and 40mg dose groups achieving the IGA 0/1 score, respectively, compared to just 9.5% in the placebo group.

Further supporting these findings, the study showed significant improvements in the biomarker TARC (CCL17) levels, which are associated with AD. The levels of TARC in the active treatment arms approached those of non-lesional skin by the end of the treatment period.

Improvements were also noted in the Eczema Area and Severity Index (EASI). Patients in the 20mg, 30mg, and 40mg groups had mean percentage changes in EASI scores of -55.1%, -52.2%, and -61.4%, respectively, compared to -50.4% in the placebo group. Although baseline EASI scores were relatively low (mean of 23), indicating less severe disease, the results in the subset of patients with more severe baseline EASI scores (>21) demonstrated a greater distinction between active treatment and placebo.

Orismilast also showed rapid onset of itch relief. At Week 2, a significant number of patients reported a ≥4-point reduction in the Numerical Rating Scale (NRS) for itch across all dose groups compared to placebo. Additionally, improvements were seen in pain and sleep NRS as well as the patient global impression of change, particularly in the 20mg group.

Kim Kjøller, Co-CEO of UNION, expressed enthusiasm about the study's outcomes, highlighting orismilast's potential as a safe and effective oral treatment for various immunological conditions. The safety profile of orismilast was consistent with previous studies and comparable to other PDE4 inhibitors, with common treatment-emergent adverse events (TEAEs) including diarrhea, nausea, and headache. These events were mostly mild and occurred primarily within the first month of treatment.

The ADESOS study was a randomized, double-blind, placebo-controlled, parallel-group trial conducted across multiple centers in Europe and the US. The study included 235 patients who were randomized to receive either 20mg, 30mg, or 40mg doses of orismilast or placebo twice daily.

Orismilast is a next-generation PDE4 inhibitor that targets the PDE4B/D subtypes, known to be involved in inflammatory processes. It has shown potent inhibition of the Th1, Th2, and Th17 pathways, which are associated with numerous dermatological and immunological diseases. UNION is developing orismilast for various conditions, including AD, hidradenitis suppurativa (HS), psoriasis, and ulcerative colitis (UC).

The FDA has granted Fast Track designation for oral orismilast for the treatment of moderate to severe AD and HS, following a successful End-of-Phase 2 meeting. This designation could expedite the drug’s development and review process, bringing a potentially valuable treatment option to patients sooner.

Overall, the positive results from the ADESOS study underline orismilast's potential as an innovative treatment for AD and possibly other inflammatory diseases, marking a significant step forward in UNION's mission to address unmet medical needs in immunology.