Date: 2014-05-23
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 11th European Academy of Dermatology and Venereology Spring Symposium in Belgrade, Serbia
Company: Pfizer (USA - NY)
Product: tofacitinib
Action
mechanism: kinase inhibitor/Janus kinase inhibitor. Tofacitinib is an oral Janus kinase (JAK) inhibitor.
Disease: psoriasis
Therapeutic area: Autoimmune diseases - Dermatological diseases
Country:
Trial
details: The Phase 3 OPT clinical trial program consists of five studies (including one long-term extension study) evaluating oral tofacitinib 5 mg and 10 mg twice daily in adults with moderate-to-severe chronic plaque psoriasis. It is a global, comprehensive clinical development program that includes over 3,600 patients in 36 countries. In addition to the OPT Retreatment study, the OPT Program includes the following Phase 3 studies of tofacitinib in adults with moderate-to-severe plaque psoriasis: OPT Pivotal #1 (A3921078) and OPT Pivotal #2 (A3921079): OPT Pivotal #1 and OPT Pivotal #2 are 52-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the safety and efficacy of tofacitinib 5 mg and 10 mg twice daily in patients who are candidates for systemic therapy or phototherapy. There were over 900 patients randomized into the each of the studies. As previously announced in April 2014, the OPT Pivotal #1 and OPT Pivotal #2 studies showed that tofacitinib, as a 5 mg or a 10 mg dose taken as a pill twice daily, met the primary efficacy endpoints of statistically significant superiority over placebo at Week 16 in the proportion of subjects achieving a PGA response of “clear” or “almost clear” skin, and the proportion of subjects achieving at least a 75% reduction in Psoriasis Area and Severity Index (PASI75). OPT Compare (A3921080):A 12-week, Phase 3 study comparing the efficacy and safety of tofacitinib 5 mg and 10 mg twice daily to high-dose ENBREL® (etanercept) 50 mg twice weekly as well as to placebo. There were 1,106 patients enrolled in this study. OPT Retreatment was a Phase 3 randomized, double-blind, three-period, parallel group, placebo-controlled 56-week study. This study evaluated the efficacy and safety of the withdrawal and retreatment with tofacitinib 5 mg and 10 mg twice daily compared to placebo in 674 adult patients with moderate-to-severe chronic plaque psoriasis. During the first period (24 weeks), which was a secondary endpoint of this study, patients were treated with either tofacitinib at a dose of 5 mg or 10 mg twice daily in a blinded manner.
OPT Extend (A3921061): A long-term extension study evaluating the safety and tolerability of tofacitinib. Patients who participated in the Phase 2 trial or any of the other Phase 3 studies had the option, if eligible, to enroll in this study.
Latest
news: * On May 23, 2014, Pfizer announced detailed results from the Oral treatment Psoriasis Trial (OPT) Retreatment study (A3921111), a Phase 3 study investigating tofacitinib for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis. This three-period study showed that tofacitinib, as a 5 mg or 10 mg pill taken twice daily, met its two primary efficacy endpoints. The safety profile of tofacitinib in OPT Retreatment was consistent with previous studies and there were no new safety findings in this trial. The first primary endpoint of OPT Retreatment evaluated the maintenance of clinical response in patients who remained on tofacitinib after an initial treatment phase compared to patients who were switched to placebo (withdrawal phase). The second primary endpoint examined patients who lost half of their original clinical response during the withdrawal phase, and measured the proportion of these patients who regained their original clinical response after restarting treatment with tofacitinib. Throughout the study, the efficacy response was measured by the proportion of subjects achieving a Physician’s Global Assessment (PGA) response of “clear” or “almost clear” skin and the proportion of subjects achieving at least a 75% reduction in the Psoriasis Area and Severity Index (PASI75), two commonly used measures of efficacy in psoriasis. During the initial 24 weeks of treatment: • 44% and 68% of patients who received tofacitinib 5 mg and 10 mg twice daily achieved at least a 75% reduction in the Psoriasis Area and Severity Index (PASI75), respectively, and • 42% and 63% of patients who received tofacitinib 5 mg and 10 mg twice daily achieved a PGA response of “clear” or “almost clear” skin, respectively. The patients who achieved a PASI75 and PGA response were then randomized to either continue tofacitinib or switch to placebo for 16 weeks or until they lost half of their original PASI response to treatment, whichever occurred first. During this withdrawal period:A statistically significantly greater proportion of patients who remained on both doses of tofacitinib maintained PASI75 and PGA responses relative to patients who were switched to placebo, and No patients experienced psoriasis rebound (rapidly spreading psoriasis after treatment withdrawal). In the retreatment period, all patients resumed their original tofacitinib dose until week 56. After 16 weeks of restarting therapy with tofacitinib, the efficacy response was evaluated in the proportion of patients who lost half of their original PASI or PGA response during the withdrawal phase and showed that: • 36.8% and 61.0% of patients who received tofacitinib 5 mg and 10 mg twice daily, respectively, achieved a PASI75; and • 44.8% and 57.1% of patients who received tofacitinib 5 mg and 10 mg twice daily, respectively, achieved a PGA of “clear” or “almost clear” skin. The results from this study will be included in the planned tofacitinib psoriasis submission package to regulatory authorities in various markets. Pfizer currently intends to submit a supplemental New Drug Application (sNDA) to the FDA for the approval of tofacitinib for the treatment of adults with moderate-to-severe chronic plaque psoriasis by early 2015.
The most common adverse events for all study periods were nasopharyngitis and upper respiratory tract infection. There was one cardiac-related death that occurred during the OPT Retreatment study at the 5 mg dose. However, in the opinion of the investigator, there was not a reasonable possibility that this death was related to tofacitinib.
