Pfizer Inc. announced detailed results from OPT Compare (A3921080), a Phase 3 study of tofacitinib, the first in a new class of treatment, oral Janus kinase (JAK) inhibitors, the safety and efficacy of which are being investigated for the treatment of adults with moderate-to-severe chronic plaque psoriasis. Top-line results from OPT Compare were previously announced in October 2013.
This is the first of five studies from the Phase 3 Oral treatment Psoriasis Trial (OPT) Program, one of the largest global clinical trial programs in moderate-to-severe chronic plaque psoriasis to date. The results of OPT Compare showed that in a step-down procedure design, tofacitinib 10 mg twice daily (BID) was non-inferior to high-dose Enbrel (etanercept) 50 mg twice weekly (BIW), and tofacitinib 5 mg twice daily did not meet the non-inferiority criteria compared to high-dose Enbrel. No new safety signals for tofacitinib were observed in the OPT Compare study. Detailed results of this study were presented as an oral presentation during the Latest in Dermatology Research Symposium at the 72nd American Academy of Dermatology (AAD) Annual Meeting held in Denver, Colo.
“We are pleased to present the detailed results of OPT Compare, the first Phase 3 trial showing non-inferiority of an oral small molecule, tofacitinib, versus an injected biologic agent, Enbrel, in psoriasis. The results demonstrated that tofacitinib 10 mg twice daily had similar efficacy to high-dose Enbrel 50 mg twice weekly,” said lead author Hervé Bachelez, Sorbonne Paris Cité Université Paris Diderot, Department of Dermatology, APHP Hôpital Saint-Louis, Paris, France.
OPT Compare is a 12-week, non-inferiority study comparing the efficacy and safety of tofacitinib 5 mg and 10 mg BID to high-dose Enbrel 50 mg BIW, the approved starting dose for Enbrel for the first 12 weeks, and placebo for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis. The results of the study showed that tofacitinib 10 mg BID was non-inferior to high-dose Enbrel 50 mg BIW as measured by Psoriasis Area and Severity Index (PASI) 75 response and Physician’s Global Assessment (PGA) response. The proportion of patients that achieved a PASI75 response at week 12 was: tofacitinib 10 mg BID: 63.6%; Enbrel 50 mg BIW: 58.8%; tofacitinib 5 mg BID: 39.5%; placebo: 5.6%.
The proportion of patients that achieved “clear” or “almost clear” in PGA at week 12 were: tofacitinib 10 mg BID: 68.2%; Enbrel 50 mg BIW: 66.3%; tofacitinib 5 mg BID: 47.1%; placebo: 15.0%. Tofacitinib 5 mg BID did not meet the non-inferiority criterion of 15% difference compared to high-dose Enbrel as measured by PASI75.
The efficacy and safety profile of tofacitinib in this study was expected based on what was seen in the Phase 2 clinical trial and dose modeling. Rates of selected safety events of special interest in the study patient population, including serious infections, herpes zoster, non-melanoma skin cancer and cardiovascular events, were below 1% and similar for all active treatment groups (both tofacitinib arms and the Enbrel arm). The most frequent adverse events across active treatment groups were infections (most commonly nasopharyngitis and upper respiratory tract infections). Injection site reactions were more frequent among patients receiving active Enbrel treatment compared with the tofacitinib and placebo arms, whereas increases in cholesterol and creatine phosphokinase were more common in tofacitinib recipients.
The detailed OPT Compare study results mark the completion of the first Phase 3 trial for tofacitinib in psoriasis. Top-line results for the second completed study, OPT Retreatment (A3921111), were previously announced in October 2013, and detailed results will be presented at a future scientific meeting. Top-line results from two of the three remaining trials in the Phase 3 Oral treatment Psoriasis Trial (OPT) Program, the OPT Pivotal 1 and OPT Pivotal 2 trials (A3921078 and A3921079), are anticipated in the second quarter of 2014, and these four studies, in addition to a long-term extension study, will form the planned psoriasis submission package to regulatory authorities.
Date: March 22, 2014