2014年10月17日讯 /生物谷BIOON/ --悲剧了！FDA审查员对辉瑞（Pfizer）提交的关于戒烟药Chantix新的安全性数据不满意，认为应该保留Chantix潜在精神方面副作用的黑框警告。FDA将在周四召开专家委员会会议，关于是否应该保留Chantix药物标签中的黑框警告征求专家意见，该黑框警告告诫消费者Chantix可能导致一些严重的精神疾病，甚至致人自杀。
Chantix是一种非尼古丁戒烟处方药，于2006年在美国上市，其成分主要是一种选择性烟碱乙酰胆碱受体部分激动剂。
FDA给安慰奖，或2015年再议黑框
FDA审查员的立场，将注定周四专家委员会会议会中会出现激烈讨论。上个月，FDA让辉瑞在Chantix标签中添加一些良好的安全性数据，给辉瑞了一丝希望，然而，目前看来，FDA的这一让步，最终可能只是一个安慰奖。
FDA审查员对辉瑞提交的数据和机构统计数据及其他提交的数据进行了审查，在一份长达398页的分析报告中，FDA审查员表示，在移除药物标签警告信息方面很少有先例，或许真的应该等到2015年对照试验的安全性数据出来之后，再商议Chantix黑框一事。该对照试验，旨在评估Chantix的相关风险。
辉瑞meta分析存局限性
FDA审查员指出，辉瑞的meta分析存在局限性，同时得出结论：辉瑞开展的观察性研究所提供的安全性证据质量欠佳，并不足以排除Chantix可能增加自杀、企图自杀或精神疾病住院的风险。
FDA审查员认为，最近报道的不良事件报告与导致Chantix黑框警告的发现一致，同时指出，在一些报告中，当患者停止服药Chantix后，神经精神方面的副作用消失了，当再次接受Chantix治疗时，副作用又出现了。
Chantix安全争议源源不断，数以千计法律诉讼
不过，该审查意见也为辉瑞留了一扇窗。FDA已经决定，这些数据中的一些信息可以被添加至Chantix的药物标签。而至于移除黑框警告嘛？这就是为什么要召开专家委员会议的原因，大家齐聚一堂商讨辉瑞的meta分析及观察性数据，是否足以推翻FDA审查员在报告中所指出的局限性。
周四的会议，仅仅是展开有关Chantix一系列安全性争议的最新讨论，Chantix于2006年上市，上市之后关于副作用的报道一直源源不断。2009年FDA在Chantix标签中添加了黑框警告。自一上市，Chantix的销售额便呈火箭般暴涨，但自从相关副作用被报道之后，其销售额大幅下滑。辉瑞称，媒体的负面关注是导致Chantix销售暴跌的直接原因。
去年，辉瑞支付了超过2.75亿美元解决指控Chantix诱发自杀、自杀念头等精神方面的数以千计的法律诉讼。但辉瑞坚持认为Chantix具有良好的疗效/风险属性。在2011年底，FDA根据新的研究数据，认为Chantix并没有增加精神疾病住院的风险。但现在，FDA确定，Chantix的黑框警告仍是必要的。
英文原文：FDA reviewers say Pfizer's Chantix should keep its black box
FDA staffers aren't as impressed with new safety data on Chantix as Pfizer ($PFE) wants them to be. In briefing documents filed in advance of Thursday's advisory committee meeting, reviewers say the stop-smoking remedy should keep its black-box warning about potential psychiatric side effects.
The reviewers' stance sets the stage for a spirited argument Thursday, where the FDA's expert advisors will consider whether to keep that black box on Chantix's label, or scrap it as Pfizer requests.
The company has reason to hope: The FDA let Pfizer add some favorable safety data to Chantix's label last month. But that concession could end up being a consolation prize.
In a 398-page analysis of data submitted by Pfizer, plus agency stats and other submissions, agency reviewers said that removing a boxed warning has "limited precedent," and that it really should wait till next year's results from a controlled trial designed to evaluate Chantix's risks.
Here's where the reviewers come down on the evidence. They point out limitations in Pfizer's meta-analyses, and conclude that the drugmaker's observational studies "provided evidence of insufficient quality" to rule out an increased risk of suicide, suicide attempt or psychiatric hospitalization.
Meanwhile, recent adverse event reports to the agency "were consistent with the findings ... that led to the current boxed warning," the reviewers write. And they point out that some of those reports show that neuropsychiatric side effects disappeared when patients stopped using Chantix, and/or recurred when therapy resumed.
The review leaves a door open for Pfizer, however. The agency "has determined that some information about these data could be included in the [Chantix] labeling." As for removing the boxed warning? That's why the committee is meeting--to see whether Pfizer's meta-analyses and observational data, given the limitations outlined in the review are enough to prompt the change, the reviewers say.
Thursday's meeting is just the latest in a series of debates over Chantix safety, thanks to side effects reports that started rolling in soon after the drug's launch in 2006. The black-box warning was added in 2009. Before the side effects reports started rolling in, Chantix was churning out sales; in fact, until Vertex Pharmaceuticals' ($VRTX) hep C drug Incivek hit the market, Chantix was the industry's fastest launch. But by last year, sales had dropped by $648 million, down slightly from 2013--and from $846 million in 2008. The company cited the "lingering impact of negative media attention" for the slide.
Last year, Pfizer paid more than $275 million to settle thousands of lawsuits alleging that Chantix triggered suicides, suicidal thoughts and other psychiatric problems. The company says it stands by the drug and its risk-benefits profile. In late 2011, based on new study data, the FDA said that the drug doesn't appear to increase the risk of psychiatric hospitalization. But at the time, the agency affirmed that the black-box warning was still necessary.