FDA拒绝批准静脉注射用抗血小板药物坎格雷洛

据药品制造商Medicines公司称，美国食品药品管理局（FDA）已拒绝批准静脉注射用抗血小板药物坎格雷洛，并建议提供更多数据。

该公司申请了两项坎格雷洛适应症：用于减少近期未接受噻吩并吡啶类药物治疗的经皮冠脉介入（PCI）治疗患者的死亡、心梗、支架内血栓以及缺血引起的血运重建；用于因手术而中断口服P2Y12抑制剂治疗导致血栓事件（例如支架内血栓）风险增加的支架置入患者。

在今年年初的会议上，FDA心血管与肾病咨询委员会以临床试验存在诸多问题为由，以7:2的投票结果反对批准第一项适应症的申请，并一致反对批准第二项适应症。

该公司4月30日在宣布FDA决定的声明中指出，FDA建议该公司对CHAMPION PHOENIX研究（为申请PCI适应症而开展的临床研究，N. Engl. J. Med. 2013;368:1303-13）开展“一系列数据分析”。此外，FDA还认为针对第二项搭桥适应症的申请，应开展一项评价坎格雷洛风险-获益的前瞻性对照研究，转归应包括出血。而该公司此前仅提交了一项小规模药效学研究结果。该研究显示，坎格雷洛输注治疗在维持血小板抑制方面与氯吡格雷相当。

该公司董事长兼总裁Clive A. Meanwell博士在声明中指出：“下一步评审将集中于针对FDA要求所进行的补充分析。”

据该公司称，坎格雷洛是一种静脉内给药的血小板P2Y12抑制剂，半衰期为3~6分钟，在停止输注后1小时内血小板功能可恢复正常。口服P2Y12抑制剂氯吡格雷具有较长的延迟作用，其作用在停药后仍可持续数天。

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By: ELIZABETH MECHCATIE, Cardiology News Digital Network

The Food and Drug Administration has rejected the approval of the intravenous antiplatelet drug cangrelor, suggesting that the company provide more data, according to the drug’s manufacturer.

The Medicines Company applied for approval of cangrelor for two indications: the reduction of death, MI, stent thrombosis, and ischemic-driven revascularization in patients who have not been recently treated with a thienopyridine and who are undergoing PCI; and for patients with stents who are at an increased risk for thrombotic events, such as stent thrombosis, when oral P2Y12 therapy is interrupted for surgery.

At a meeting earlier this year, the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 7-2 against approval of the first indication, and unanimously voted against approval of the second indication, citing numerous issues with clinical trials.

The company’s April 30 statement announcing the FDA decision said that the agency had suggested that the company conduct "a series of data analyses" from the CHAMPION PHOENIX study that was the basis of the PCI indication (N. Engl. J. Med. 2013;368:1303-13).

The FDA also concluded that a prospective controlled study to evaluate the risk-benefit of cangrelor for the second bridging indication with outcomes that included bleeding was needed, the statement said. For this indication, the company had submitted only a small pharmacodynamic study, which showed that a cangrelor infusion could maintain platelet inhibition similar to that achieved with clopidogrel.

In the statement Dr. Clive A. Meanwell, the company’s chairman and chief executive officer, said that "the next steps of review will focus on additional analyses in response to the FDA."

Cangrelor is a platelet P2Y12 inhibitor administered intravenously; with a half-life of 3-6 minutes, platelet function returns to normal within 1 hour of stopping the infusion of cangrelor, according to the company. The oral P2Y12 inhibitor clopidogrel has a more delayed action, with activity that lasts for days after is stopped.