- Orismilast Phase 2b results in atopic dermatitis (AD) presented today as a late-breaking oral presentation at the European Academy of Dermatology and Venerology (EADV) Congress 2024
- Orismilast demonstrated clear treatment effect with statistical significance for all dose arms on the registrational endpoint of IGA0/1 at week 16
- Orismilast also demonstrated fast onset of itch reduction as measured by ≥4 point reduction in NRS at week 2 with statistical significance for all dose arms
- Biomarkers including TARC (CCL17) improved statistically significantly for all orismilast doses compared with placebo
- Safety and tolerability in line with prior studies with orismilast as well as marketed PDE4-inhibitors, positioning orismilast uniquely as a safe and efficacious oral treatment
- Orismilast has previously demonstrated efficacy in both psoriasis and hidradenitis suppurativa (HS), and is also being studied in ulcerative colitis (UC)
- Following a positive End-of-Phase 2 meeting with the FDA, UNION plan to progress orismilast to Phase 3 development in AD
Hellerup, Denmark, September 25, 2024, – UNION therapeutics A/S (“UNION”), a privately held, clinical stage, pharmaceutical development company focused on immunology, today announces results from the ADESOS Phase 2b study with orismilast in adults with moderate to severe atopic dermatitis presented by Prof. Dr. Eric Simpson at the EADV Congress 2024.
Data from the 233 patients randomized and dosed in the study demonstrated that significantly more patients achieved Investigator Global Assessment (IGA) 0/1 responses at Week 16 in orismilast 20mg (n=58), 30mg (n=61), and 40mg (n=59) groups, compared to placebo (n=55) (26.3%, 24.3%, 30.9%, and 9.5%, respectively; all p-values <0.05). Additionally, the efficacy observed using the IGA score was supported by changes in skin levels of TARC (CCL17/thymus and activation-regulated chemokine) – a key disease biomarker of AD. Data showed that TARC skin levels are significantly reduced in the active arms, with end of treatment levels approaching those of non-lesional skin.
Mean percentage changes in EASI (Eczema Area and Severity Index) at Week 16 were: -55.1%, -52.2%, -61.4%, and -50.4%, in orismilast 20, 30, 40mg and placebo groups, respectively (p>0.05). Mean EASI at baseline was 23, the least severe reported in a Phase 2b/3 study in moderate to severe AD to date. This likely drove the high EASI placebo response also seen in other recent studies with more moderate patients. In the subgroup of patients with severe disease at baseline (EASI >21), active arms separated from placebo on EASI as well as other endpoints.
Additionally, all active arms demonstrated a significant ≥4-point reduction in itch Numerical Rating Scale (NRS) at Week 2, compared to placebo (p <0.05). Additional patient-reported outcomes, including change in pain and sleep NRS, as well as patient global impression of change, were significantly improved in the 20 mg group at Week 2. Most patients with AD report itch as the worst symptom of their disease and therefore reporting a fast onset of action on itch and other patient reported outcomes is important to improving patient quality of life.
“The results from the ADESOS study with orismilast in atopic dermatitis (AD) follows positive read outs in psoriasis and hidradenitis suppurativa (HS) confirming the potential of orismilast as a safe oral treatment option across immunology”, says Kim Kjøller, Co-CEO of UNION. “We are excited that the results have been presented today as a late-breaking oral presentation by Prof. Dr. Eric Simpson at the EADV Congress 2024. It is always a pleasure being at the conference and discussing the results with leading experts within the field as we plan to progress orismilast to Phase 3 development in atopic dermatitis.”
No new safety signals were identified, and the safety profile was aligned with that seen for the PDE4 class. The most common TEAE’s were diarrhea, nausea, and headache, mainly seen within the first month, mostly mild in severity, with few leading to treatment discontinuation. The safety and tolerability profile of orismilast was confirmed and consistent with the PDE4-class and what was seen in the IASOS study of orismilast in psoriasis and OSIRIS study of orismilast in HS.
About the ADESOS Phase 2b study
The Phase 2b study is a randomized, double-blind, placebo-controlled, parallel-group, dose-finding study to evaluate the efficacy and safety of orismilast in patients with moderate to severe AD. The study included 235 patients who were randomized to three active doses (20mg, 30mg, and 40 mg) of orismilast or placebo administered twice daily. The study was conducted in centers in Europe and in the US.
About orismilast
Orismilast is a next generation, high potency PDE4 inhibitor targeting the PDE4B/D subtypes linked to inflammation, demonstrating potent inhibition of Th1, Th2 and Th17 pathways. It acts early in the inflammation cascade, inducing a broad range of anti-inflammatory effects across multiple cytokines involved in many dermatological and immunological diseases.1) Orismilast is developed to have more potent anti-inflammatory properties than previously marketed PDE4 inhibitors, enabled by higher selectivity for subtypes PDE4B and D.
UNION is developing orismilast as an oral treatment, based on the well-known safety profile of the PDE4 class, across immunology, initially targeting best-in-class or first-in-class positions in atopic dermatitis (AD), hidradenitis suppurativa (HS), psoriasis and ulcerative colitis (UC).
The FDA has cleared UNION’s Investigational New Drug (IND) application for oral orismilast and granted Fast Track designation for oral orismilast for the treatment of moderate to severe AD as well as for the treatment of moderate to severe HS.
About atopic dermatitis
AD is a chronic inflammatory skin disease affecting 2.1-4.9 % of the adult population worldwide and is the most common skin disease among children.2) There was approximately 20 million diagnosed moderate-to-severe adult patients with AD in 2023 in the Seven Major Markets (US, France, Germany, Italy, Spain, UK, and Japan).3) Disease symptoms are characterized by recurrent eczematous skin lesions and intense itch. AD has a substantial psychosocial impact on patients and relatives.4) During disease flares, approximately 80% of patients may experience disturbed sleep, which may also disrupt the sleep of family members.5) The disease also appears to impact the mood, and patients have an increased risk of anxiety and depression.6)
Sources
1) Blauvelt A et al., Dermatology and Therapy 2023: Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review – PubMed (nih.gov) &
Silverberg J.I. et al., JEADV 2022: https://onlinelibrary.wiley.com/doi/10.1111/jdv.18818 &
Warren R.B. et al., JEADV 2022: https://onlinelibrary.wiley.com/doi/10.1111/jdv.18812
2) Barbarot S et al,. Allergy 2018: https://pubmed.ncbi.nlm.nih.gov/29319189/ https://pubmed.ncbi.nlm.nih.gov/25925336/
3) EvaluatePharma 2023
4) Laughter MR et al., British Journal of Dermatology 2021: https://pubmed.ncbi.nlm.nih.gov/33006135/
5) Eichenfield LF et al., Journal of the American Academy of Dermatology 2014: https://pubmed.ncbi.nlm.nih.gov/24290431/
6) Drucker AM et al., The Journal of Investigative Dermatology 2017: https://pubmed.ncbi.nlm.nih.gov/27616422/
Contacts
Morten Boesen, Chief Financial Officer, UNION therapeutics A/S
+45 2381 5487
Sarah Toft-Jørgensen, Director of Communications and IR, UNION therapeutics A/S
+45 5385 3044
About UNION therapeutics
UNION therapeutics is a privately held, clinical stage, pharmaceutical development company focused on immunology. UNION’s lead asset is orismilast, a next generation, high potency PDE4B/D inhibitor, for a range of immunological diseases e.g., atopic dermatitis (AD) and hidradenitis suppurativa (HS). Orismilast holds the potential to become the first safe oral treatment in AD.
UNION is headquartered in Hellerup, Denmark, and led by an international team combining biotech entrepreneurs and seasoned pharma executives, with a track record of developing and launching more than fifteen marketed drugs. Read more at http://www.uniontherapeutics.com
