- Clinical Trials
- Research News
- Industry Trends
- Agency Actions
- Drug Safety Issues
- Approvals, Launches, & New Indications
- Health Care Reform
Positive Phase II Results for Psoriasis Drug Ponesimod
Disease severity significantly reduced versus placebo (Dec. 18)
The selective sphingosine 1-phosphate receptor 1 (S1P1) modulator ponesimod (Actelion Pharmaceuticals) has met the primary efficacy endpoint — the proportion of patients with at least 75% improvement in the Psoriasis Area and Severity Index (PASI) from baseline (PASI 75) at week 16 — in a double blind, placebo-controlled study of 326 patients with moderate-to-severe chronic plaque psoriasis.
At week 16, 46% of patients treated with once-daily ponesimod 20 mg and 48% of patients treated with once-daily ponesimod 40 mg improved by at least 75% compared with 13% of placebo-treated patients (both P < 0.0001).
At the end of induction, ponesimod-treated patients who improved by at least 50% or more on the PASI at week 16 were re-randomized to continuation of the same dose of ponesimod or to placebo.
After the initial 16-week induction phase of the study, further improvement was seen with ponesimod during the 12-week double-blind, placebo-controlled maintenance period. Among patients continuing on ponesimod 20 mg and 40 mg, 71% and 77% achieved PASI 75 at the end of the study, respectively.
At the initiation of ponesimod treatment, transient reductions in heart rate and a transient effect on atrioventricular conduction were observed. The most common adverse events associated with ponesimod were dose-dependent dyspnea and asymptomatic liver enzyme elevations.
Psoriasis is a chronic, relapsing, inflammatory and immune-mediated skin disease affecting approximately 1% to 3% of the population worldwide. Plaque psoriasis is the most common form of psoriasis, constituting about 85% of cases. The disorder’s most characteristic skin lesions are sharply demarcated, erythematous plaques covered by silvery white scales. The plaques most commonly occur on the elbows, knees, scalp, umbilicus, and lumbar area. Children, adolescents, and adults are affected.
Sphingosine-1-phosphate (S1P) is a sphingolipid released by erythrocytes, platelets, mast cells, and other cell types. S1P stimulates at least five cell-surface resident G–protein–coupled receptors (GPCRs) — S1P1, 2, 3, 4, and 5. Activation of these GPCRs mediates a variety of biological responses, including lymphocyte migration, endothelial cell proliferation, blood vessel constriction, and heart rate modulation.
Ponesimod is an orally active, selective S1P1 immunomodulator. The drug prevents lymphocytes from leaving lymph nodes, thereby reducing circulating blood lymphocyte counts and preventing the infiltration of lymphocytes into target tissues.
Source: Actelion Pharmaceuticals; December 18, 2012.