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This randomized, double-blind, placebo-controlled trial assessed the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of multiple oral doses of VTP-43742 in patients with moderate to severe psoriasis over a four-week period. VTP-43742 demonstrated a clear signal of efficacy, with patients in the 350 mg dose group achieving a 24 percent reduction in the Psoriasis Area Severity Index (PASI) score relative to placebo. In the 700 mg dose group, patients achieved a 30 percent placebo-adjusted PASI score reduction. For both doses, we observed clinically relevant and statistically significant reductions (p<0.015) relative to baseline values.Between weeks zero and two, there was a modest onset of PASI reduction, and for the last weeks of the study, and particularly between weeks three and four, there was an acceleration of the rate of reduction in PASI score in both the 350 mg and 700 mg dose groups, suggesting the potential for greater reductions in PASI scores with longer duration of treatment. While full efficacy in psoriasis is not generally seen until at least 12 weeks of continuous therapy, the PASI score reductions observed for VTP-43742 at four weeks, and the acceleration of rate of PASI reduction between weeks three and four, are consistent with the potential to achieve greater oral efficacy in the treatment of psoriasis. VTP-43742 was shown to be generally well tolerated at all dose levels tested, with no serious adverse events reported. No drug-related electrocardiogram (ECG) abnormalities were observed. In the 700 mg dose group, reversible transaminase elevations were observed in four patients. Pharmacokinetics were consistent with once-a-day dosing.


In biomarker assays measuring plasma IL-17A and IL-17F, the 350 mg and 700 mg doses of VTP-43742 were shown to decrease both plasma cytokines by up to 75 percent, and these decreases were statistically significant (p<0.02), consistent with the change in PASI score from baseline.