orismilast oral (LEO 32731) / LEO Pharma, UNION Therap, Innovent Biologics - LARVOL DELTA

Study to Assess the Efficacy and Safety of Orismilast in Atopic Dermatitis (ADESOS) (clinicaltrials.gov) - P2 | N=235 | Completed | Sponsor: UNION therapeutics | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2

Phase classification • Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Population Pharmacokinetic-Pharmacodynamic (popPK/PD) Relationship of Orismilast, A Potent and Selective PDE4B/D Inhibitor, in Atopic Dermatitis. (PubMed, Dermatol Ther (Heidelb)) - "The outcome of the analysis supports the observed clinical effect of orismilast in patients with AD and could explain the lack of efficacy of apremilast in the same indication."

Journal • PK/PD data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • IL13

UNION therapeutics announces presentation of preliminary data from Phase 2a investigator-initiated study with orismilast in ulcerative colitis at the 20th ECCO Congress (PRNewswire) - "UNION therapeutics...today announced a poster presentation on new clinical data of oral orismilast in patients with UC at the 20th European Crohn's and Colitis Organisation (ECCO) congress on February 19-22, 2025, in Berlin, Germany. UCORIS is a Phase 2a, open-label, investigator-initiated study investigating the efficacy and safety of oral orismilast for up to 12 weeks in adult patients with moderate and severe UC. Following the inclusion of 10 patients, the enrollment for the study has stopped with the study expected to be completed in 2025."

P2a data • Trial completion date • Inflammatory Bowel Disease • Ulcerative Colitis

Orismilast for the treatment of moderate to severe Ulcerative Colitis: Analysis of preliminary data from UCORIS, a phase 2a, open-label, single-arm exploratory clinical trial (ECCO-IBD 2025) - "Across all patients included in the study, 3 out of 9 (33%) achieved remission following treatment with orismilast; however, two of these three patients discontinued treatment due to adverse events (headache and nausea). In conclusion, these preliminary data suggest that orismilast shows potential as a treatment for UC, with one patient reaching the primary endpoint and two others achieving remission."

Clinical • P2a data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Orismilast May be an Effective Novel Therapy for Atopic Dermatitis (Dermatology Advisor) - P2b | N=210 | ADEOS (NCT05469464) | Sponsor: UNION therapeutics | "Orismilast may be an effective, novel treatment option for atopic dermatitis (AD), according to the results of a phase 2b trial published in the British Journal of Dermatology...The ADESOS study (ClinicalTrials.gov Identifier: NCT05469464) was a randomized, placebo-controlled phase 2b trial conducted at 48 sites in Europe and the United States...At week 16, EASI scores had decreased by 55.1%, 52.2%, and 61.4% among the low-, intermediate-, and high-dose orismilast groups compared with 50.4% among the placebo group. Significantly more patients receiving the low (7.0%; P <.05) and intermediate (8.4%; P <.05) doses achieved a 100% improvement in EASI from baseline relative to those who received placebo (0%)...More patients in the low- (26.3%; P <.05) and high-dose (30.9%; P <.05) orismilast groups achieved an Investigator Global Assessment (IGA) score of 0 or 1 (IGA 0/1) and a 2-point or more..."

P2b data • Atopic Dermatitis

UNION therapeutics announces full-year results for 2024 (Cision) - "The promise of orismilast as a potent PDE4B/D inhibitor continued to garner attention from medical leaders in the dermatological research community, with the initial results from the ADESOS Phase 2b study selected for late-breaking oral presentations at prominent scientific conferences, and the results from the OSIRIS Phase 2a study in hidradenitis suppurativa accepted for publication in the Journal of the European Academy of Dermatology and Venereology, a globally leading journal within dermatology....The company is now planning the next stage of development for orismilast, which includes shaping the clinical development and regulatory strategy. Focus is initially on hidradenitis suppurativa, a devastating inflammatory skin disease with very few treatment options available and no oral treatments approved, leaving a significant unmet medical need."

P2a data • P2b data • Atopic Dermatitis • Hidradenitis Suppurativa • Immunology

Orismilast for moderate-to-severe atopic dermatitis: the potential therapeutic value of a new oral pharmacological alternative. (PubMed, Br J Dermatol) - No abstract available

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology. (PubMed, Pharmaceutics) - "Apremilast was the first PDE4 inhibitor approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for psoriasis, psoriatic arthritis, and oral ulcers of Behcet's disease. New oral PDE4 inhibitors are being developed, such as orismilast (LEO-32731), mufemilast (Hemay005), difamilast (OPA-15406) or lotamilast (E6005/RVT-501), among others. This narrative review provides a comprehensive synthesis of the pharmacology, clinical efficacy, safety profile, and practical considerations regarding the oral and topical use of PDE4 inhibitors in dermatology."

Journal • Review • Atopic Dermatitis • Chronic Obstructive Pulmonary Disease • Dental Disorders • Dermatitis • Dermatology • Dermatopathology • Discoid Lupus Erythematosus • Hidradenitis Suppurativa • Immunology • Inflammation • Inflammatory Arthritis • Lichen Planus • Lupus • Psoriasis • Psoriatic Arthritis • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Rheumatology • Sarcoidosis • Seborrheic Dermatitis • Seronegative Spondyloarthropathies • Stomatitis

Orismilast, a PDE4B/D inhibitor, in moderate-to-severe atopic dermatitis: Efficacy and safety from a multicenter, randomized, placebo-controlled, phase 2b dose-ranging study (ADESOS). (PubMed, Br J Dermatol) - P2b | "These data support the clinical relevance of selective PDE4B/D inhibition with orismilast, potentially offering a convenient, novel, oral therapy for the treatment of AD."

Journal • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pruritus

Innovations in Psoriasis. (PubMed, Dermatol Clin) - "This review discusses therapies that were recently Food and Drug Administration (FDA)-approved for treating psoriasis, including the topical agents tapinarof and roflumilast, deucravacitinib, an oral small molecule that selectively inhibits tyrosine kinase 2, and spesolimab, a monoclonal antibody inhibiting interleukin-36 that became the first FDA-approved treatment for generalized pustular psoriasis flares. Other therapies are in the pipeline, such as orismilast, as well as Mind.Px, a tool for predicting biological response, is also highlighted."

Journal • Review • Dermatology • Immunology • Psoriasis • Pustular Psoriasis • TYK2

Acceptable Clinical Trial Differences vs Placebo in Plaque Psoriasis (EADV 2024) - "When compared to various clinical trial results for apremilast, deucravacitinib, JNJ-2113, orismilast, and ME3183, all molecules are at or nearly meeting dermatologists ’ minimally acceptable range, apart from apremilast. With a substantial armamentarium for biologics in psoriasis,** physicians express a need for efficacious and safe oral options for PsO. Current late-stage assets and deucravacitinib meet dermatologists ’ minimum threshold for improvement, however, only JNJ-2113 100mg meets the delta considered to be a significant advance over the standard of care. Data suggests JNJ-2113 would fill an unmet need if approved."

Clinical • Dermatology • Immunology • Psoriasis • KEAP1

Molecular effects in the skin of atopic dermatitis patients after oral treatment with orismilast (EADV 2024) - P2b | "This biomarker evaluation, based on tape strip skin samples from patients with AD participating in the Phase 2b ADESOS study, demonstrate a reduced level of multiple cytokines and chemokines across several immune pathways. We consider the significant reduction observed for TARC particularly important and supportive of the clinical efficacy observed for orismilast as serum TARC levels has been described as the most reliable disease severity biomarker in AD.2 Finally, the study underlines tape strip sampling of the skin as a powerful, non-invasive technology to obtain data on protein changes when used in combination with the Olink® technology. 1 ) Silverberg et al."

Clinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CCL20

Efficacy and safety of orismilast, a potent PDE4B/D inhibitor, in adults with moderate-to-severe atopic dermatitis: a phase 2b randomized, double-blinded, placebo-controlled clinical trial (ADESOS) (EADV 2024) - "Orismilast inhibits PDE4-B/D isoforms up to 39 times more potently than apremilast, leading to potent suppression of Th1, Th17, and Th2 effector cytokines. Orismilast demonstrated early itch reduction NRS ≥ 4 and statistically significant efficacy versus placebo at Week 16 as measured by IGA0/1. The study was impacted by a high EASI placebo rate; however, in severe patients, the 20 and 40 mg doses separated from placebo for EASI75 and EASI90 measurements, consistent with the overall findings as measured by IGA 0/1, patient-reported efficacy, and objective biomarkers. No new safety signals were identified, and the profile was aligned with the well-established experience from the PDE4 inhibitor class."

Clinical • P2b data • Atopic Dermatitis • Dermatitis • Dermatology • Gastrointestinal Disorder • Immunology • Infectious Disease • Pain • Psoriasis

Orismilast efficacy in adults with moderate-to-severe atopic dermatitis in a phase 2b trial: early impact on itch and patient-reported outcomes (EADV 2024) - "Introduction & Objectives: Orismilast is a potent selective phosphodiesterase 4 (PDE4)-B and -D inhibitor, which showed significant efficacy in a Phase 2b psoriasis study.1,2 Orismilast inhibits PDE4-B/D isoforms up to 39 times more potently than apremilast,1 leading to potent suppression of Th1, Th17, and Th2 effector cytokines.1 Here, efficacy of oral orismilast was evaluated versus placebo in adults with moderate-to-severe AD. Orismilast demonstrated early reduction in itch, significant for all doses as early as Week 2. Early improvements were also demonstrated for pain, sleep, and patient global impression of change, as well as a statistically significant efficacy versus placebo at Week 16 as measured by IGA 0/1. The high EASI placebo rate seen in this trial was decreased in severe patients, and the 20 and 40 mg doses separated from placebo for EASI75 and EASI90 measurements, consistent with the overall findings as measured by IGA 0/1, patient-reported efficacy,..."

Clinical • Late-breaking abstract • P2b data • Patient reported outcomes • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Pain • Psoriasis

UNION therapeutics announce results from the ADESOS Phase 2b study in atopic dermatitis confirming the potential of orismilast as a first-in-class safe and efficacious oral treatment (PRNewswire) - P2b | N=210 | ADESOS (NCT05469464) | UNION therapeutics | "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..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)."

P2b data • Atopic Dermatitis • Dermatitis • Immunology

UNION therapeutics to present orismilast Phase 2b results in atopic dermatitis as a late-breaking oral presentation at the EADV Congress 2024 (PRNewswire) - "UNION therapeutics A/S (UNION)...today announced ADESOS Phase 2b results selected as a late-breaking oral presentation at the European Academy of Dermatology and Venerology (EADV) Congress 2024 on September 25-28, 2024, in Amsterdam, Holland. New data from the ADESOS Phase 2b study of orismilast in AD will be presented by Prof. Dr. Eric Simpson. The efficacy and safety results of orismilast from the Phase 2b ADESOS trial will also be presented as an poster. Additionally, one poster on the molecular effects in the skin of AD patients after oral orismilast treatment will be presented."

P2b data • Atopic Dermatitis • Immunology

UNION therapeutics announces successful completion of the ADESOS Phase 2b study and presentation of data at the RAVE Conference 2024 (PRNewswire) - "UNION therapeutics A/S...today announces successful completion of the ADESOS Phase 2b, randomized, dose-finding study evaluating orismilast as an oral treatment in 233 patients with moderate-to-severe AD. Topline results from the ADESOS study have been selected for an oral presentation by the Signatory Investigator, Professor Jonathan Silverberg, MD, PhD, MPH at the late breaking research sessions at Revolutionizing Alopecia Areata, Vitiligo, and Eczema (RAVE) Conference on June 8-10, 2024, in Chicago, United States. It will be the first presentation of data from the ADESOS study....UNION has scheduled an End of Phase 2 meeting with the FDA to discuss advancing the orismilast development program into Phase 3 studies in AD."

FDA event • P2b data • Trial completion • Atopic Dermatitis • Immunology

IASOS: Study to Assess the Efficacy and Safety of Orismilast in Psoriasis (clinicaltrials.gov) - P2 | N=202 | Completed | Sponsor: UNION therapeutics | Phase classification: P2b ➔ P2

Phase classification • Dermatology • Immunology • Psoriasis • Psoriatic Arthritis

UNION therapeutics announces publication of results from the OSIRIS Phase 2 study of orismilast in hidradenitis suppurativa in the Journal of the European Academy of Dermatology and Venereology - "Professor Gregor B Jemec, MD...principal investigator of the study said: 'Hidradenitis suppurativa is an inflammatory systemic skin disease where a strong unmet need remains for safe and effective oral treatments. Data from the Phase 2 study with orismilast in HS indicates PDE4-inhibition is a relevant mode of action for HS, and that at the right dose regimen, orismilast may be a promising treatment for HS.'"

Media quote • Hidradenitis Suppurativa

Orismilast for the treatment of mild to severe hidradenitis suppurativa: Week 16 data from OSIRIS, a Phase 2a, open-label, single-centre, single-arm, dose-finding clinical trial. (PubMed, J Eur Acad Dermatol Venereol) - P2 | "Oral orismilast demonstrated a dose-dependent tolerability, with mild to moderate adverse effects. Further, the results of this exploratory trial indicate that orismilast may lead to clinical improvements in HS. However, larger trials with tolerable dose ranges are warranted. The Trial is registered at Clinicaltrials.gov (UNI50007201) and EudraCT.ema.europa.eu (2021-000049-42)."

Journal • P2a data • Dermatology • Hidradenitis Suppurativa • Immunology

Orismilast shows early efficacy in plaque psoriasis (Healio) - "'Despite a growing number of available systemic treatments for moderate to severe psoriasis, significant undertreatment and persistent unmet therapeutic needs exist,' Richard B. Warren, BSc, MBChB, PhD...and colleagues wrote. '[PDE4] enzymes, with subtypes regulating inflammatory pathways, are involved in the pathogenesis of psoriasis.'"

Media quote • Psoriasis

Good news for over 50,000 Danes who live with painful skin disease [Google Translation] (Sundhedspolitisk Tidsskrift) - "According to Gregor Jemec, this clinical study speaks to an ongoing positive development, where more treatment options are on the way. The disease has so far very few effective treatment options, and the patients have been an overlooked group for many years. But research into the prevalence of hidradenitis suppurativa (HS) has helped push treatment options in a positive direction. Around one percent of the population globally has HD." "

Media quote • Hidradenitis Suppurativa

Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, phase 2b trial (IASOS). (PubMed, J Am Acad Dermatol) - P2b | "Orismilast demonstrated greater efficacy versus placebo and a safety profile in line with PDE4 inhibition."

Clinical • Journal • P2b data • Dermatology • Immunology • Psoriasis

Study to Assess the Efficacy and Safety of Orismilast in Atopic Dermatitis (ADESOS) (clinicaltrials.gov) - P2b | N=210 | Active, not recruiting | Sponsor: UNION therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

UNION Therapeutics to present new data on orismilast at EADV Congress 2023 in Berlin (Pharmabiz) - "Professor Gregor B. Jemec...and sponsoring investigator of the study, says: 'A strong unmet need remains for a safe and effective oral treatment for hidradenitis suppurativa. The promising topline results from the OSIRIS study illustrates that potent PDE4 inhibition by orismilast offers the potential for additional efficacy in combination with a well-known safety profile from the PDE4 class.'"

Media quote • Hidradenitis Suppurativa