Union plans Phase III trial for atopic dermatitis after Phase IIb success

Union Therapeutics is making strides in the development of its phosphodiesterase-4 (PDE4) inhibitor, orismilast, intending to advance it into a Phase III clinical trial for atopic dermatitis (AD). This decision follows encouraging outcomes from a Phase IIb study, which assessed the efficacy and safety of orismilast in treating AD.

The Danish pharmaceutical company is not limiting its investigation of orismilast to AD alone. The therapy is also being explored for its potential in treating other dermatological and inflammatory conditions, such as psoriasis, hidradenitis suppurativa, and ulcerative colitis.

As the next step, Union Therapeutics aims to commence a Phase III trial for orismilast in AD, contingent upon the approval of the trial design by the US Food and Drug Administration (FDA). This approval will be sought during an end-of-Phase II meeting. The promising results from the Phase IIb ADESOS trial (NCT05469464) were unveiled at the European Academy of Dermatology and Venerology (EADV) 2024 Congress, held from September 25 to 28 in Amsterdam, Netherlands.

Kim Kjøller, co-CEO of Union Therapeutics, emphasized the significance of these findings, noting that the positive results in AD are in line with earlier successful outcomes in psoriasis and hidradenitis suppurativa. According to Kjøller, these consistent results underscore orismilast's potential as a safe and effective oral treatment option across various immunological conditions.

Orismilast, a PDE4 inhibitor, exerts its effects by modulating multiple inflammatory mediators, thereby reducing inflammation. In 2021, Union entered into a licensing agreement with Innovent Biogics, granting them the development and marketing rights for orismilast in China, in a deal valued at over $267 million.

The Phase IIb ADESOS trial involved 233 patients suffering from moderate to severe atopic dermatitis. These participants were randomly assigned to receive one of three doses of orismilast (20mg, 30mg, or 40mg) or a placebo. The study achieved its primary endpoint by demonstrating a reduction in the eczema area and severity index (ESAI) after 16 weeks of treatment. Specifically, the mean percentage reduction in ESAI was -55.1% for the 20mg group, -52.2% for the 30mg group, and -61.4% for the 40mg group, compared to a -50.4% reduction in the placebo group. The high placebo response was attributed to the high disease severity at baseline, with an average ESAI of 23.

Furthermore, the study met its secondary endpoint by achieving clear (0) or almost clear (1) responses in the Investigator Global Assessment for AD (IGA-AD) at 16 weeks. The results showed that 26.3%, 24.3%, and 30.9% of participants in the 20mg, 30mg, and 40mg orismilast groups, respectively, attained 0/1 scores in IGA-AD, compared to just 9.5% in the placebo group.

The treatment groups also exhibited a significant reduction in CCL17/thymus and activation-regulated chemokine (TARC) skin levels, a biomarker for AD, with end-of-treatment levels nearing those found in non-lesional skin. Additionally, participants in orismilast groups reported a four or more-point decrease in the itch numerical rating scale (NRS) two weeks post-treatment.

Despite the positive outcomes, the study noted some common treatment-associated adverse effects, including diarrhea, nausea, and headache.

Union Therapeutics remains optimistic about the future of orismilast, as they prepare to advance it into the next phase of clinical trials, potentially offering a new, effective treatment option for patients with atopic dermatitis and other inflammatory conditions.