Orismilast shows early efficacy in plaque psoriasis

Key takeaways:

• Orismilast, a phosphodiesterase 4 inhibitor, exhibited efficacy in psoriasis patients at 20 mg, 30 mg and 40 mg doses.
• Patients had statistically significant improvements in PASI and IGA scores.

The efficacy of orismilast is greater than placebo in patients with moderate to severe psoriasis, according to phase 2b trial results.

The multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2b trial evaluated orismilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in 202 patients with psoriasis who were randomly assigned to receive 20 mg, 30 mg or 40 mg doses of the drug or placebo twice daily for 16 weeks.

“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, FRCP, of the Northern Care Alliance NHS Foundation Trust and the National Institute of Health and Care Research Manchester Biomedical Research Centre, and colleagues wrote. “[PDE4] enzymes, with subtypes regulating inflammatory pathways, are involved in the pathogenesis of psoriasis.”

Orismilast, which belongs to a newer class of PDE4 inhibitors, selectively inhibits PDE4B and PDE4D, the two subtypes most notably involved in inflammation.

Patients completed a screening visit at least 28 days before the beginning of the trial. Patients were then seen on day 1 and then every 4 weeks through the 16-week treatment period and again at week 20 for follow-up.

The trial’s primary endpoint was a percentage change in PASI. Also, secondary endpoints included a 75% reduction in PASI score (PASI 75) and an IGA score of 0 or 1 (clear or almost clear), along with a 2-point or more improvement in IGA.

Of the 202 patients who began the trial, 62.4% completed it.

Patients treated with orismilast 20 mg, 30 mg or 40 mg had a –52.6%, –61.2% and –63.7% change in PASI score, respectively, compared with –17.3% in those treated with placebo at week 16 (P < .001).

PASI 75 was achieved by 39.5%, 49% and 46.4% of the three respective treatment groups, compared with 16.5% of the placebo group (P < .05 for all), whereas PASI 90 was achieved in 24.1% of the 20 mg group, 22% of the 30 mg group, 28.3% of the 40 mg group and 8.3% of the placebo group (P < .05 for 20 mg and 40 mg groups).

PASI100 was achieved by 8.7%, 8.9% and 4.3% of the treatment groups and 2.2% of the placebo group.

IGA 0/1 was recorded in 26.2% of the 20 mg cohort, 24.5% of the 30 mg cohort and 20.6% of the 40 mg cohort, compared with 6.9% of the placebo group. This was statistically significant for the 20 mg and 30 mg groups (P < .05 for both).

Additionally, dose-dependent reductions in body weight were observed in the treatment groups with hip circumference reductions seen in all dose groups.

The most common adverse events included gastrointestinal events, headaches and dizziness with most being mild and occurring withing the first 4 weeks of treatment.

Discontinuations were similar for placebo and the 20 mg and 30 mg dose cohorts but increased for the 40 mg dose group.

“In this study, orismilast [twice a day] demonstrated significant efficacy vs. placebo at week 16 in patients with moderate to severe plaque psoriasis for percentage change in PASI, and proportions achieving PASI 75 and PASI 90,” Warren and colleagues wrote.

“These data support the potential of selective PDE4B/D inhibition as a promising therapeutic option in psoriasis and the further development of orismilast for the treatment of plaque psoriasis,” the authors concluded.