Union Therapeutics is set to advance its phosphodiesterase-4 (PDE4) inhibitor, orismilast, into a Phase III clinical trial for atopic dermatitis (AD) after promising outcomes from its Phase IIb ADESOS trial (NCT05469464). The company is awaiting FDA approval of the trial design following an end-of-Phase II meeting.
The Phase IIb study, presented at the European Academy of Dermatology and Venerology (EADV) 2024 Congress, enrolled 233 patients with moderate to severe atopic dermatitis. Participants were administered one of three doses of orismilast (20mg, 30mg, or 40mg) or a placebo.
Efficacy and Safety Profile
The trial met its primary endpoint, demonstrating a reduction in the eczema area and severity index (EASI) at 16 weeks. The 20mg, 30mg, and 40mg orismilast groups achieved mean percentage reductions in EASI of -55.1%, -52.2%, and -61.4%, respectively, compared to a -50.4% reduction in the placebo group. Union Therapeutics attributed the high placebo response to the high disease severity at baseline, with a mean EASI of 23.
Kim Kjøller, co-CEO of Union, stated, “The results from the ADESOS study with orismilast in AD follows positive readouts in psoriasis and hidradenitis suppurativa confirming the potential of orismilast as a safe oral treatment option across immunology.”
Secondary Endpoints and Biomarkers
The study also met its secondary endpoint, with 26.3%, 24.3%, and 30.9% of participants in the 20mg, 30mg, and 40mg orismilast groups achieving a clear (0) or almost clear (1) response in the Investigator Global Assessment for AD (IGA-AD) at 16 weeks, compared to 9.5% in the placebo group.
Furthermore, treatment groups exhibited a reduction in CCL17/thymus and activation-regulated chemokine (TARC) skin levels, a biomarker of AD, with end-of-treatment levels approaching those of non-lesional skin. Patients in the orismilast groups also experienced a four or more-point reduction in the itch numerical rating scale (NRS) two weeks post-treatment. Common adverse effects included diarrhea, nausea, and headache.
Orismilast's Mechanism and Broader Potential
Orismilast functions as a phosphodiesterase-4 (PDE4) inhibitor, influencing multiple inflammatory mediators that cause a pro-inflammatory effect. In 2021, Union Therapeutics licensed the development and marketing rights for orismilast in China to Innovent Biologics in a deal valued at over $267 million. Union Therapeutics is also exploring orismilast for other dermatological and inflammatory conditions, including psoriasis, hidradenitis suppurativa, and ulcerative colitis.
