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FDA宣布暂停销售白血病治疗药物ponatinib

Sales of leukemia drug suspended because of treatment-associated vascular events
来源:爱思唯尔 2013-11-05 14:33点击次数:628发表评论

10月31日,美国食品药品管理局(FDA)宣布,鉴于与普纳替尼(ponatinib)相关的“危及生命的血栓和血管重度狭窄”风险,FDA已经要求生产商暂停这种白血病治疗药物的销售和推广。


这距离普纳替尼加速审批还不到1年的时间。去年12月该药获准用于对既往酪氨酸激酶抑制剂(TKI)治疗耐药或不耐受的慢性期、加速期或急变期慢性粒细胞性白血病(CML),以及对既往TKI治疗耐药或不耐受的费城染色体阳性急性淋巴细胞性白血病(Ph+ ALL)。


Lesley M. Arnold 博士
 
普纳替尼是一种激酶抑制剂,由ARIAD Pharmaceuticals公司生产销售,商品名为Iclusig。FDA声明称其近期开展的一项调查显示,自该药获批以来,血栓和血管狭窄事件不断增加。一名FDA发言人表示,在批准该药时,只有14%的患者出现这类事件,而现在生产商开展的2项临床试验表明发生率分别达到了24%和48%。


FDA建议,对治疗没有应答的患者应立即停药,与医生讨论其他治疗方案。如果患者对治疗有应答,并且“医生判定治疗的潜在效益大于其风险”,则应该在单个患者在研新药(IND)申请或者扩大获取登记计划下进行治疗。


声明称,在一项中位随访时间为1.3年的Ⅱ期试验以及一项中位随访时间为2.7年的Ⅰ期试验中,分别约有24%和48%的患者出现了严重不良血管事件,包括致命性和危及生命的心肌梗死、卒中、肢体血流中断致组织坏死,以及“肢体、心脏和大脑血管重度狭窄需要行紧急手术以恢复血流”。无论是伴或不伴心血管危险因素的患者都出现了这类事件。试验中,67%的患者经普纳替尼治疗后出现了高血压;8%出现了心衰,包括致死性病例。


普纳替尼的处方信息中含有一个黑框警告,提醒与治疗相关的动脉血栓形成和肝脏毒性风险。


FDA指出:“我们将继续评估该药以进一步了解其风险,并且确定该药对于哪些患者人群而言可能利大于弊。”


ARIAD在10月31日公布的另一份声明中确认了公司暂时停止普纳替尼的销售和推广。该公司“相信Iclusig对于那些耐药或不耐受的费城阳性白血病患者是一种很重要的药物,目前正在积极配合FDA的工作以恢复Iclusig的销售”。


与普纳替尼相关的严重不良事件应通过互联网或电话800-332-0178报告给FDA网上可以查询有关IND计划的信息。


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By: ELIZABETH MECHCATIE, Internal Medicine News Digital Network


The Food and Drug Administration has asked the manufacturer of ponatinib to suspend sales and marketing of the leukemia drug because of the risk of "life-threatening blood clots and severe narrowing of blood vessels" associated with the drug, the agency announced Oct. 31.


The request comes less than a year since the expedited approval of ponatinib for the treatment of chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy, or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to prior tyrosine kinase inhibitor therapy.
 
Ponatinib is a kinase inhibitor, marketed as Iclusig by ARIAD Pharmaceuticals. A recent FDA investigation determined that, since the drug was approved in December 2012, blood clots and narrowing of blood vessels have increased, according to the FDA statement. At the time of approval, 14% of patients on the drug experienced these events, according to an agency spokesperson. Two of the company’s clinical trials are now showing rates of 24% and 48%.


Patients who are not responding to treatment should be taken off the drug immediately and discuss alternative treatment with their clinicians, the agency has advised. In addition, patients who are responding to treatment, "whose health care professionals determine that the potential benefits outweigh the risks," should be treated under a single-patient Investigational New Drug (IND) application or expanded access registry program, the statement said.


About 24% of patients treated with ponatinib over a median of 1.3 years in a phase II study and about 48% of the patients in a phase I study treated for a median of 2.7 years have had serious adverse vascular events, which include fatal and life-threatening MIs, stroke, loss of blood flow to the extremities resulting in tissue death, "and severe narrowing of blood vessels in the extremities, heart, and brain requiring urgent surgical procedures to restore blood flow," the statement said. These events have been reported in patients with and without cardiovascular risk factors. In studies, 67% of treated patients have developed hypertension; and 8% have developed heart failure, including fatal cases.


The prescribing information for the drug includes a boxed warning about the risk of arterial thrombosis and hepatotoxicity associated with treatment.


"We will continue to evaluate the drug to further understand its risks and potential patient populations in which the benefits of the drug may outweigh the risks," the FDA noted.


In a separate Oct. 31 statement, ARIAD confirmed that it was temporarily suspending sales and marketing of ponatinib. The company "believes that Iclusig is an important medicine for patients with resistant or intolerant Philadelphia-positive leukemias and is actively working with the FDA on actions to achieve the resumption of marketing of Iclusig," the company stated.


The prescribing information for the drug includes a boxed warning about the risk of arterial thrombosis and hepatotoxicity associated with treatment.


Serious adverse events associated with ponatinib should be reported online to the FDA or by phone, 800-332-0178. Information about the IND program is available online.


学科代码:血液病学 药学   关键词:ponatinib 血栓和血管重度狭窄 白血病治疗药物
来源: 爱思唯尔
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