A potential first-in-class or best-in-class treatment for immunological skin diseases
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.
Orismilast has been selected as lead molecule based on its attractive therapeutic window (i.e., the combination of improved efficacy and tolerability) and because of its potential to inhibit many inflammatory pathways involved in immunologic diseases due to the broad range of anti-inflammatory effects.
Over the course of Phase 1 and Phase 2 trials, orismilast has been demonstrated to be safe in both oral and topical dosage forms and the PDE4 mode-of-action has been verified as an effective, well-tolerated approach to treatment of patients across multiple diseases, with no need for monitoring.
UNION is developing orismilast as an oral formulation for the treatment of AD, HS and psoriasis.
Mild-to-Moderate
13,4M suffers from Psoriasis in the US, EU5 and Japan
PDE4 inhibitor
Dermatology market and include
topical roflumilast cream
PDE4 Market and include
topical roflumilast cream
Moderate-to-servere
People in the US suffer from Psoriasis
TNF-Q + 11-17
Plaque psoriasis and atopic
dermatitis
Acim quam ratem eos dis ma
doluptatist
Checkpoint-for Psoriasis
People in EU5 suffer from Psoriasis
Keratinoc
Exerting anti-inflammatory effect
reducing psoriasis scale formation
PDE4 Market and include
topical roflumilast cream
Orismilast development programs
The current development status of oral orismilast is the following:
- AD: The FDA has granted Fast Track designation to oral orismilast for the treatment of moderate to severe AD, and UNION initiated a Phase 2b dose finding study in July 2022. The ClinicalTrials.gov Identifier is NCT05469464
- HS: The FDA has granted Fast Track designation to oral orismilast for the treatment of moderate to severe HS. Positive topline results reported on June 21, 2023, for OSIRIS (PoC, IIT) study for oral orismilast in HS. The study demonstrated clinically relevant improvements in HS for patients who completed the planned 16 weeks of treatment with oral orismilast. Importantly, the improvements included reduction of pain (Global Pain Assessment) and improvement in patient-reported quality of life (DLQI). ClinicalTrials.gov Identifier: NCT04982432
- Psoriasis: Phase 2b topline results reported on January 9, 2023, supporting the target product profile of orismilast and confirming the well-established favorable safety profile of PDE4 inhibition. In November 2020, the US Food and Drug Administration (FDA) approved UNION’s Investigational New Drug Program (IND) for advancing oral orismilast into a Phase 2b trial in patients with moderate to severe psoriasis. ClinicalTrials.gov Identifier: NCT05190419
UNION has also tested orismilast as a topical formulation in a Phase 2a study. In the Phase 2a proof-of-concept study in AD topical orismilast demonstrated statistically significant efficacy compared to placebo with no stinging, burning or pain at the application site.
The importance of selective PDE4B/D inhibitors
Dr. Andrew Blauvelt, Dermatologist, investigator and president of the Oregon Medical Research, talks about the next-generation of PDE4 inhibitors.
Preclinical and Phase 2a data on orismilast
Professor of Dermatology Jonathan Silverberg presented new data on orismilast at the 31st EADV Congress, 7-10 September 2022.
Publications
Blauvelt A et al., Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review – PubMed (nih.gov) Dermatology and Therapy 2023:
Silverberg J.I. et al. (2022), Pharmacology of orismilast, a potent and selective PDE4 inhibitor, JEADV
Warren, R.B. et al. (2023), Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, phase 2b trial (IASOS), JAAD 2023
Warren R.B. et al. (2022), Efficacy and safety in moderate-severe psoriasis and development of modified release tablets, JEADV
