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首页 » 心血病药物市场 » FDA对强生拜瑞妥(Xarelto)ACS适应症持谨慎态度

FDA对强生拜瑞妥(Xarelto)ACS适应症持谨慎态度

来源:生物谷 2014-01-16 09:30

2014年1月16日讯 /生物谷BIOON/ --FDA似乎对强生(JNJ)所提交的关于抗凝血剂拜瑞妥(Xarelto)用于治疗急性冠脉综合征(ACS)的数据持怀疑态度。强生所提交的这些数据,旨在用于证明,对于那些在近期已遭受了一次心脏病发作的患者群体,Xarelto能够有效地降低进一步的心脏问题的风险。

FDA质疑强生分析临床实验数据的方法,并表示没有令人信服的证据来证明Xarelto能够提供显著的临床利益或填补未获满足的医疗需求,因为市场上还有其他药物。

FDA内部审查员于周三在其网站上发布了审查意见,而FDA外部专家顾问委员会将在周五举行会议讨论是否建议批准该药。

目前,Xarelto已获批用于治疗和预防深静脉血栓和肺动脉栓塞,同时获批用于并非由心脏问题引发的不规则心脏跳动患者,以降低中风风险和减少血液凝块。现在,强生希望FDA批准Xarelto用于急性冠脉综合征(ACS)。

强生最初于2011年底提交了Xarelto用于治疗ACS的适应症申请,但FDA拒绝了该申请,称疗效数据并没有强大到足以支持该适应症的获批。随后,强生提交了额外的数据,但FDA再次拒绝批准,促使强生对FDA的审查提出上诉。

FDA驳回了强生的上诉,但表示如果将Xarelto的使用持续时间限制至1个月,可能是该药获批的一个途径,因为在此期间内,Xarelto疗效更显著,同时出血、药物副作用风险较低。而强生提交的申请中,Xarelto的使用持续时间为90天。

FDA内部的最新审查表明,该机构仍然存怀疑态度。FDA审查发现,目前还不清楚如何选择度量,来确定何时Xarelto的临床利益是最大的。不仅仅因为Xarelto在早期没有更显著的效果,而且在头90天左右效果不明显。而强生认为,当把Xarelto添加至标准疗法时,能显著降低心血管事件风险(包括死亡),从而提供一个强有力的增量效益。

FDA的审查,还质疑了强生Xarelto升高的出血风险是否能远远超过该药所提供的临床益处,因为其他2种药物,礼来(Eli Lilly)的Effient(普拉格雷)和阿斯利康(AstraZeneca)的Brilinta(替卡格雷)已获批用于急性冠脉综合征(ACS)。

强生拟议的处方信息警告,因还没有开展Xarelto与Effient和Brilinta联合用药的研究,鉴于出血风险的存在,不推荐与后2者联合用药。因此,Xarelto将只能用作百时美施贵宝(BMS)的抗凝血剂Plavix(氯吡格雷)的一种附加药物。

而FDA认为,没有数据表明,Xarelto+Plavix联合治疗组ACS患者比Effient或Plavix治疗组患者有更优越的善后。因此,Xarelto并不能填补未获满足的医疗需求。尽管在限制的治疗持续时间内有一个直观的吸引力,但Xarelto疗效随持续时间的分析任务,并不在于挑出一个利益-风险比尚可接受的时间段。(生物谷Bioon.com)

英文原文:FDA staff cautious about J&J's latest Xarelto application

(Reuters) - The U.S. Food and Drug Administration appears skeptical that data submitted by Johnson & Johnson proves its anticoagulant Xarelto is effective in reducing the risk of further heart problems in patients who have recently suffered a heart attack.

The agency questioned the way in which J&J analyzed clinical trial data, and said there was no convincing proof the drug confers significant benefit or fills an unmet medical need, given that there are other therapies on the market.

The review was posted on the FDA's website on Tuesday, two days ahead of a meeting of outside experts who will discuss the drug, also known as rivaroxaban, and recommend whether it should be approved.

   Xarelto is already used to treat and prevent deep vein thrombosis and pulmonary embolisms and to reduce the risk of stroke and blood clots in patients with an irregular heart beat that is not caused by heart problems.

Now the company is hoping it will also be approved for patients with acute coronary syndrome (ACS), an umbrella term covering any condition brought on by a sudden, reduced blood flow to the heart, including heart attack and chest pain.

Some analysts are doubtful.

"Based on our review of this material, we continue to have low expectation of approval," Larry Biegelsen, an analyst at Wells Fargo Securities, said in a research note. However, he expects sales of the drug to rise to $1.2 billion in 2015 from an estimated $703 million in 2013 based on the indications for which it is approved.

"We expect the ACS potential to be modest even if approved," he said.

J&J originally filed for approval of Xarelto in ACS at the end of 2011. The FDA rejected the application, saying efficacy data was not strong enough to support approval. The company provided additional information but the FDA once again declined to approve the drug, prompting J&J to appeal the decision.

The FDA denied the appeal but said limiting the duration of use to one month might be a pathway forward because efficacy was more evident and the risk of bleeding, a side effect of the drug, was lower during this period. J&J filed a new application seeking a treatment duration of 90 days.

The FDA's latest review suggests the agency remains skeptical.

"It is unclear how to choose the metric for determining when the benefit of rivaroxaban is greatest," the review found. "Not only does the effect of rivaroxaban not appear to be greater earlier, but an effect in the first 90 days or so is not apparent at all."

Dr. Paul Burton, vice president of clinical development at Janssen Research and Development, a J&J unit, defended the drug, saying the company believes that when added to standard treatments it "delivers a strong incremental benefit by significantly reducing the risk of cardiovascular events, including death, at a time when patients are at the highest risk."

The FDA's review also questioned whether the benefit of the drug outweighs the heightened risk of bleeding since two other drugs, Eli Lilly & Co's Effient and AstraZeneca Plc's Brilinta, are currently approved for ACS.

J&J's proposed prescribing information would warn that treatment in combination with the Effient, known also as prasugrel, and Brilinta, also known as ticagrelor, has not been studied and is not recommended because of the risk of bleeding.

Xarelto would therefore only be available as an add-on to Bristol-Myers Squibb Co's antiplatelet Plavix, or clopidogrel.

"There are no data demonstrating that ACS patients treated with clopidogrel plus rivaroxaban will have superior outcomes compared to treatment with prasugrel or ticagrelor," the review said. "So rivaroxaban does not provide therapy for an unmet medical need."

And while treatment for a limited duration "has an intuitive appeal," the review said, "the task for the analyses of the effect of rivaroxaban over time is not to pick a time period in which the benefit-risk is acceptable."

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