ST LOUIS (MD Consult) - The US Food and Drug Administration (FDA) has licensed RiaSTAP, an orphan drug, for treating bleeding in patients with a rare genetic defect known as congenital fibrinogen deficiency.

Without treatment, these patients are at risk of potentially life-threatening bleeding.

People with congenital fibrinogen deficiency are unable to make sufficient amounts of fibrinogen, which plays an important role in blood coagulation by helping to form blood clots and prevent bleeding. Fibrinogen is manufactured in the liver and circulates in the blood plasma in a normal concentration of 250-400 mg/dL.

"This product offers much-needed treatment for the small number of patients with congenital fibrinogen deficiency," said Jesse Goodman, MD, MPH, director of the FDA's Center for Biologics Evaluation and Research. "If bleeding occurs in the brain or other organs and is left untreated, it may lead to blood loss, organ damage and death."

Fibrinogen deficiency only affects 150 to 300 people in the United States and is usually diagnosed at birth when newborns bleed from their umbilical cord site. Children with the defect need to curtail activities because of risk of bleeding from minor trauma.

RiaSTAP is an intravenous fibrinogen concentrate made from the plasma of healthy human blood donors. The product is indicated for patients who have no fibrinogen or low levels of the substance, an abnormality known as afibrinogenemia, or for those patients whose fibrinogen levels are below 50 mg/dL, a condition known as hypofibrinogememia.

The product is not indicated for patients with dysfibrinogenemia, who may have normal fibrinogen levels but defective fibrinogen function. Patients such as these are at risk for bleeding and clotting complications.

The licensing of RiaSTAP was supported by a study of 15 patients with afibrinogenemia who achieved the target level of fibrinogen expected to prevent bleeding after they received 70 mg/kg of the drug. In addition, plasma from 14 of the 15 patients showed increased maximum clot firmness, a surrogate marker likely to predict clinical benefit. Fever and headache were the most common adverse reactions.

Clinical benefit will be further verified in a postmarketing study that will include both afibrinogenemic and hypofibrinogenemic patients.

Orphan drugs are drugs or biologics intended for use in a rare disease or condition. Manufacturers are qualified to receive certain government benefits in exchange for developing such products. RiaSTAP [Fibrinogen Concentrate (Human)] was developed under the FDA's accelerated approval regulations.

The drug is manufactured by CSL Behring, Marburg, Germany. 

圣路易斯(MD Consult）——美国食品与药物管理局（FDA）批准罕用药物RiaSTAP用于治疗罕见遗传性缺陷即先天性纤维蛋白原缺乏症患者的出血症状。如果不进行治疗，此类患者存在致命性出血的潜在风险。

纤维蛋白原可促进血块形成和防止出血，因此在血液凝固过程中起重要作用。先天性纤维蛋白原缺乏症患者自身无法产生足够数量的纤维蛋白原。纤维蛋白原在肝脏中产生，血浆中的正常浓度为250～400 mg/dL。

FDA生物制品评估和研究中心主任Jesse Goodman 博士称：“该产品为数量很少的先天性纤维蛋白原缺乏症患者提供了急需的治疗方案。如果此类患者出血发生于脑部或其他器官后未得到治疗，可能会引起失血、器官损伤甚至死亡。”

在美国仅有150～300例纤维蛋白原缺乏症患者。此类患者通常是在出生时因发生脐带部位出血而确诊。存在此缺陷的儿童需要限制活动以降低因微小创伤发生出血的风险。

RiaSTAP是一种静脉应用的纤维蛋白原浓缩液，提取自健康人的血浆。该产品适用于无纤维蛋白原或纤维蛋白原水平低的无纤维蛋白原血症患者，或纤维蛋白原水平低于50 mg/dL的低纤维蛋白原血症患者。

该产品并不适用于异常纤维蛋白原血症患者，此类患者的纤维蛋白原水平正常，但是纤维蛋白原功能存在缺陷，因此存在出血或凝血并发症风险。

RiaSTAP的批准是基于一项纳入15例无纤维蛋白原血症患者的研究结果。该研究结果显示，患者在接受RiaSTAP 70 mg/kg剂量治疗后，纤维蛋白原达到了防止出血的预期目标水平。此外，15例患者中有14例血浆检测结果显示最大血块硬度（可能预测临床益处的替代指标）增加。RiaSTAP的最常见不良反应为发热和头痛。

RiaSTAP的临床益处将在一项上市后研究中进一步验证。该研究将纳入无纤维蛋白原血症和低纤维蛋白原血症两类患者。

罕用药（Orphan drugs）是指应用于治疗罕见疾病的药物或生物制品。研发此类产品的制造商有资格从政府部门获得特定利益以作为交换。RiaSTAP[纤维蛋白原浓缩液（人源性）]的开发符合FDA加速批准规则。

该药由德国马尔堡的CSL Behring公司制造。

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