来源：生物谷 2014-04-29 10:20
2014年4月23日讯 /生物谷BIOON/ --辉瑞（Pfizer）4月22日公布了口服Janus激酶（JAK）抑制剂tofacitinib（托法替尼，商品名：Xeljanz）的2项III期研究的顶级数据：OPT Pivotal-1 (A3921078) 和OPT Pivotal-2 (A3921079)，这些研究是III期OPT（口服治疗银屑病）项目5个III期研究中的2个研究，旨在调查tofacitinib治疗中度至重度慢性斑块型银屑病成人患者的疗效和安全性。OPT项目是迄今为止在中度至重度慢性斑块型银屑病中开展的全球最大的临床试验项目。
OPT Pivotal-1 (A3921078) 和OPT Pivotal-2 (A3921079)研究数据表明，与安慰剂相比，tofacitinib 5mg和10mg每日2次（BID）疗法，在主要疗效终点表现出统计学意义的显著改善。主要疗效终点包括第16周时受试者达到医生整体评估得分量表（Physician's Global Assessment）反应为“清除”或“几乎清晰”、以及银屑病面积和严重程度指数（Psoriasis Area and Severity Index）至少减少75%的患者比例，这是评价银屑病疗效最常用的2种方法。研究中，未发现新的安全性信号。
2013年10月，辉瑞公布了tofacitinib III期OPT项目中前2项III期研究OPT Compare (A3921080)和OPT Retreatment (A3921111)的的顶级数据，2项研究均达到了主要终点。
英文原文：Pfizer Announces Positive Top-Line Results From Two Phase 3 Trials Of Tofacitinib In Adults With Moderate-to-Severe Chronic Plaque Psoriasis
OPT Pivotal #1 and OPT Pivotal #2 Studies, Together with Three Other Phase 3 Trials, to Form Basis for Planned Psoriasis Indication Submission to Regulatory Authorities
Tuesday, April 22, 2014 - 8:00am EDT
Pfizer Inc. (NYSE:PFE) announced today top-line results from two pivotal Phase 3 trials from the Oral treatment Psoriasis Trials (OPT) Program, OPT Pivotal #1 (A3921078) and OPT Pivotal #2 (A3921079), evaluating the efficacy and safety of tofacitinib, an oral Janus kinase (JAK) inhibitor, the first in a new class of medicines being investigated for the treatment of moderate-to-severe plaque psoriasis. 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 Physician’s Global Assessment response of “clear” or “almost clear,” and the proportion of subjects achieving at least a 75% reduction in Psoriasis Area and Severity Index, two commonly used measures of efficacy in psoriasis.
No new safety signals for tofacitinib were observed in the OPT Pivotal #1 or OPT Pivotal #2 studies. Detailed analyses of these studies, including additional efficacy and safety data, will be submitted for presentation at a future scientific meeting.
“Psoriasis is a long-term disease with no cure that can have a significant impact on patients. Although it is one of the most common chronic inflammatory diseases, many psoriasis patients remain untreated, undertreated or dissatisfied with their treatment, according to recently published surveys,” said Dr. Steven Romano, Global Medicines Development Lead for the Pfizer Global Innovative Pharmaceutical business. “Tofacitinib is the first in a new class of investigational psoriasis treatments, and I am encouraged by our Phase 3 results to-date that demonstrate the potential of tofacitinib to be an important new treatment option for adults with moderate-to-severe chronic plaque psoriasis.”
Top-line results from the first two studies from the OPT Program, OPT Compare and OPT Retreatment, were previously announced in October 2013, and these four studies, in addition to a long-term extension study, will form the planned psoriasis submission package to regulatory authorities in various markets. Pfizer currently intends to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for the approval of tofacitinib 5 mg and 10 mg twice-daily for the treatment of adults with moderate-to-severe chronic plaque psoriasis by early 2015.
About OPT Pivotal #1 (A3921078) and OPT Pivotal #2 (A3921079)
OPT Pivotal #1 and OPT Pivotal #2 were Phase 3, 52-week, multi-site, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the safety and efficacy of tofacitinib 5 mg and 10 mg twice-daily in patients with moderate-to-severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. There were over 900 patients randomized into each of the studies.
About the OPT Clinical Trial Program
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, and is one of the largest global clinical trial programs in moderate-to-severe chronic plaque psoriasis to date. In addition to the OPT Pivotal #1 and OPT Pivotal #2 studies, the OPT Program includes the following Phase 3 studies of tofacitinib in adults with moderate-to-severe chronic plaque psoriasis:
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.
OPT Retreatment (A3921111): A Phase 3 study evaluating the efficacy and safety of the withdrawal from, and then the retreatment with, tofacitinib 5 mg and 10 mg twice-daily compared to placebo.
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.
About Plaque Psoriasis
Psoriasis is a chronic, immune-mediated disease, affecting the skin and other organs, such as nails and joints. It affects approximately two-to-three percent of people worldwide and 7.4 million people in the United States.1,2,3,4,5,6,7 Due to inconsistent response to treatment, adverse effects, and the limited persistence of therapeutic effects of some therapies, a need for additional therapies for patients with moderate-to-severe chronic plaque psoriasis still remains.8,9,10 According to recently published surveys, approximately 50% of patients with psoriasis are dissatisfied with their treatment, and under-treatment represents a significant problem. Even though guidelines typically state that moderate-to-severe patients are candidates for systemic therapy – e.g., medicines given by mouth or an injection - many treated adult plaque psoriasis patients appear to be undertreated, with approximately 30% of treated moderate patients and 22% of treated severe patients receiving only topical therapies, like ointments and creams, in the U.S.11
XELJANZ® (tofacitinib citrate) RA U.S. Label Information
Tofacitinib is approved in more than 20 countries around the world for the treatment of moderate-to-severe rheumatoid arthritis. In the U.S., the brand name for tofacitinib is XELJANZ® (ZEL’ JANS’) 5 mg tablets, and it is approved for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.
XELJANZ is a prescription medicine called a Janus kinase (JAK) inhibitor. XELJANZ is used to treat adults with moderately to severely active rheumatoid arthritis in which methotrexate did not work well.
It is not known if XELJANZ is safe and effective in people with Hepatitis B or C.
XELJANZ is not for people with severe liver problems.
It is not known if XELJANZ is safe and effective in children.