Vitae Pharmaceuticals, Inc. shared positive top-line results from its Phase 2a proof-of-concept clinical trial of VTP-43742 in psoriatic patients. VTP-43742 is Vitae's wholly owned, first-in-class, orally active RORγt inhibitor with the potential to transform the treatment of multiple autoimmune disorders, including psoriasis, through the potent inhibition of IL-17 secretion from Th17 cells and blocking the action of IL-23.

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 700mg 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 700mg dose group, reversible transaminase elevations were observed in four patients. Pharmacokinetics were consistent with once-a-day dosing.

“We believe these data validate RORγt as an exciting and novel therapeutic target for the treatment of psoriasis and other autoimmune disorders,” said Jeff Hatfield, President and Chief Executive Officer of Vitae. “While the autoimmune market is currently dominated by injectable antibody therapy, we believe VTP-43742 has the potential to expand utilization of oral therapy in a variety of autoimmune disorders, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease with an effective, safe and well tolerated, once-a-day agent.”

In biomarker assays measuring plasma IL-17A and IL-17F, the 350mg and 700mg 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.

“We plan to advance VTP-43742 into a larger scale 16 week trial in the second half of 2016 to continue to assess the efficacy, safety and tolerability of our first-in-class drug candidate,” said Dr. Richard Gregg, Chief Scientific Officer of Vitae. “We look forward to presenting the complete results of this Phase 2a trial at future medical meetings.”