TY - JOUR
T1 - Orismilast in moderate-to-severe psoriasis
T2 - Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS)
AU - Warren, Richard B.
AU - French, Lars E.
AU - Blauvelt, Andrew
AU - Langley, Richard G.
AU - Egeberg, Alexander
AU - Mrowietz, Ulrich
AU - Hunter, Hamish J.A.
AU - Gooderham, Melinda
AU - Soerensen, Per
AU - Andres, Philippe
AU - Sommer, Morten O.A.
AU - Carlsson, Anna
AU - Kjøller, Kim D.
AU - Strober, Bruce E.
N1 - Publisher Copyright:
© 2023 American Academy of Dermatology, Inc.
PY - 2024
Y1 - 2024
N2 - BackgroundOrismilast is a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis.ObjectiveTo evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis.MethodsThis multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation.ResultsOf 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast –52.6% to –63.7% and placebo, –17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed.LimitationsSmall sample size, disease severity imbalance between groups, limited duration and diversity in study population.ConclusionOrismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition.
AB - BackgroundOrismilast is a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis.ObjectiveTo evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis.MethodsThis multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation.ResultsOf 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast –52.6% to –63.7% and placebo, –17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed.LimitationsSmall sample size, disease severity imbalance between groups, limited duration and diversity in study population.ConclusionOrismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition.
KW - Oral administration
KW - PDE4 inhibitors
KW - PDE4B
KW - PDE4D
KW - Psoriasis
KW - Treatment efficacy
U2 - 10.1016/j.jaad.2023.11.005
DO - 10.1016/j.jaad.2023.11.005
M3 - Journal article
C2 - 37951245
AN - SCOPUS:85175643746
SN - 0190-9622
VL - 90
SP - 494
EP - 503
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 3
ER -