FDA批准Marqibo治疗急性淋巴细胞性白血病

美国食品药品管理局(FDA)于8月9日批准Marqibo（一种脂质体包裹的长春新碱）用于治疗复发性和难治性费城染色体阴性的成人急性淋巴细胞性白血病(ALL)。

Marqibo被批准用于复发≥2次或≥2种化疗方案治疗失败的患者。这是一种允许进行剂量强化治疗的长春新碱纳米颗粒剂型，是由南加州旧金山市的Talon Therapeutics公司生产的。

Richard Pazdur博士

每年大约有6,000例成人被诊断为ALL；费城染色体阴性的类型比较少见。Talon公司估计每年约有500例患者适于接受Marqibo治疗。FDA将其视为一种罕见病药物。 “Marqibo为对现有治疗无应答的费城染色体阴性的ALL患者提供了一种治疗选择，”FDA药物评估与研究中心的血液病与肿瘤药品办公室主管Richard Pazdur博士说。

这一药物是经过FDA加速审批而获得批准的。FDA称，这种药物对一种可能预测临床效益的替代终点（应答率）具有一定疗效。但在3月份，FDA的肿瘤药物顾问委员会对Marqibo的反应冷淡，部分原因为专家小组对其疗效的印象不够深刻。根据FDA的声明，在一项Ⅱ期研究纳入的65例患者中，10例(15%)发生完全应答或完全应答伴血细胞计数不完全恢复。应答持续的中位时间为28天。中位至发生首次复发、死亡或下次治疗时间为56天。

另外，FDA的顾问也对药物安全性存有顾虑，指出试验中76%的患者发生严重不良事件，如中性粒细胞减少、低血压、呼吸窘迫和心搏骤停。该药物还带有一个加框警告，指出应通过静脉途径用药，因为采用其他方式给药可能发生致死效应，尤其是脑脊液中用药。而且Marqibo的用药剂量建议与单纯的硫酸长春新碱注射剂不同，为了避免药物过量，应在用药之前核对药品名称和剂量，FDA指出。Talon公司在一项声明中指出，该药物的应用剂量为每次2.25 mg/m²在1小时内经静脉用药，每7天重复1次。

“这一缺乏有效治疗的血液恶性疾病患者人群将可以得到Marqibo的治疗，我们对此感到非常欣喜，”Talon公司总裁兼首席执行官Steven R. Deitcher博士在声明中说。

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By: ALICIA AULT, Oncology Practice

The Food and Drug Administration on Aug. 9 approved Marqibo, a liposomal encapsulated version of vincristine, to treat relapsed and refractory Philadelphia chromosome–negative acute lymphoblastic leukemia in adults.

Marqibo was approved for patients who have relapsed twice or more, or whose disease has failed at least two chemotherapy regimens. A nanoparticle formulation of vincristine that allows for dose-intensive treatment, it is manufactured by Talon Therapeutics of South San Francisco, Calif.
 
Acute lymphoblastic leukemia (ALL) is diagnosed in about 6,000 adults each year; the Philadelphia chromosome negative type is rare. Talon estimated that about 500 patients a year would be eligible for Marqibo therapy. The FDA designated it as an orphan drug.

"Marqibo provides an additional option for Philadelphia chromosome–negative acute lymphoblastic leukemia patients whose disease is unresponsive to available therapies," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement.

The drug was approved under the agency’s accelerated approval regulations. The FDA said that the data showed that Marqibo had an effect on a surrogate end point – in this case, the response rate – that was likely to predict clinical benefit.

But Marqibo received lukewarm backing from the FDA’s Oncologic Drugs Advisory Committee in late March, in part because the panelists were not impressed with its efficacy.

According to the FDA’s approval statement, of 65 patients enrolled in a phase II study, 10 (15%) had either a complete remission or complete remission with incomplete blood count recovery. The median duration of remission was 28 days. The median time to the first event of relapse, death, or next therapy was 56 days, said the FDA.

The FDA advisers also were concerned about safety, noting that 76% of patients in trials had serious adverse events such as neutropenia, hypotension, respiratory distress, and cardiac arrest. The drug will carry a boxed warning that it should only be administered intravenously because it is deadly if administered in other ways, in particular into the spinal fluid.

The warning states that Marqibo has different dosage recommendations than does vincristine sulfate injection alone. To avoid overdose, drug name and dosing should be verified before administration, said the agency.

Talon said in a statement that the drug should be given at a dose of 2.25 mg/m2 intravenously over 1 hour once every 7 days.

"We are delighted that Marqibo will be available to a patient population with an underserved hematologic malignancy," Dr. Steven R. Deitcher, Talon president and chief executive officer, said in the statement.