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New phase 2b data show the oral PDE4 inhibitor could reduce psoriasis area severity by more than 60% in 16 weeks.
Investigative oral PDE4 inhibitor orismilast provided significant improvement in psoriasis skin clearance in treated patients versus placebo at 16 weeks, according to findings from a phase 2b trial.
The data, presented during late-breaking sessions at the American Academy of Dermatology (AAD) 2023 Annual Meeting in New Orleans this week, showed that nearly 50% of patients receiving a 40 mg dose of the pill achieved ≥90% skin clearance—indicating a potentially new and highly potent agent in plaque psoriasis care.
Presented by study author Lars French, MD, professor and chairman of the Department of Dermatology at Munich University of Ludwig Maximilian in Germany, investigators sought to evaluate the efficacy and safety of a modified-release orismilast oral tablet versus placebo in adults with moderate to severe psoriasis.
Patients with psoriasis and atopic dermatitis are characterized by overexpression of the PDE4B and PDE4D isoforms in the skin—making orismilast, an inhibitor of both those pathways, an ideal candidate for treatment.
“When compared with apremilast, orismilast is at least 2-5 fold more potent on all PDE4 isoforms and up to 39 times more potent on some of the PDE4B/D isoforms,” investigators wrote. “Orismilast showed a broad anti-inflammatory effect by inhibiting the secretion of Th1, Th17, and Th2 effector cytokines.”
The randomized, double-blind, placebo controlled IASOS trial placed 202 patients into 4 different treatment arms:
Eligible adult patients had a diagnosis of moderate to severe psoriasis characterized by Psoriasis Area Severity Index (PASI) ≥12, body surface area (BSA) ≥10%, and Investigators Global Assessment (IGA) severity ≥3 at baseline. Patients were additionally eligible for systemic treatment or phototherapy.
The trial’s primary end point was percentage change in PASI score from baseline to 16 weeks, with secondary end points being PASI-75 and ≥2-point improvement in IGA at 16 weeks. The team additionally sought safety and tolerability outcomes.
Median patient age was 43.5 years old; 147 (72.8%) patients were male and 180 (89.1%) were White. Median disease duration at baseline was 17.0 years, and median PASI and BSA scores were 18.4 and 22.25% at baseline, respectively.
Mean percent change of PASI from baseline to week 16 were as follow for each treatment arm:
The observed PASI reductions were statistically significant for all 3 orismilast arms (P <.001). PASI improvements up to -38% versus baseline were observed by week 4.
Per multiple imputation analysis, 39%, 49% and 45% of patients receiving 20 mg, 30 mg and 40 mg orismilast achieved PASI-75 at 16 weeks, respectively. Another 24%, 22% and 28%, respectively, achieved PASI-90.
What’s more, approximately one-fourth of treated patients (26%, 25% and 21%, respectively) achieved IGA scores of 0 or 1, versus just 7% of patients on placebo (P <.05).
Regarding safety, the most common adverse events were diarrhea, nausea and headaches, but were generally mild in severity. A total of 41 patients experienced a treatment-emergent adverse event that led to orismilast discontinuation. Tolerability was considered dose-dependent across the 3 treatment arms.
Nonetheless, investigators identified no new safety signals relative to prior studies, and concluded the outcomes were highly beneficial for the prospective agent as a potential psoriasis drug.
“This confirms high potency PDE4 B/D inhibition with orismilast, as a potential new oral addition to the psoriasis armamentarium, for the first time offering significant PASI-90 response,” they concluded.
Warren R, French L, Blauvelt A, et al. Efficacy and Safety of Orismilast in Patients with Moderate-to-Severe Psoriasis: Results from the Phase IIb IASOS Trial. Paper presented at: American Academy of Dermatology 2023 Annual Meeting; March 17 – 21. New Orleans, LA. Accessed March 19, 2023.