HEME ARGINATE IN ACUTE PORPHYRIA

本项目的目的是研究血红素精氨酸治疗急性卟啉症(急性间歇性卟啉症、杂色性卟啉症和遗传性盆腔炎)的疗效。血红素精氨酸酯(Normosang(R)，Leiras)是一种稳定的静脉使用的血红素制剂，它是在欧洲开发和研究的，用于治疗急性卟啉症，但尚未在美国上市。目前被FDA批准为治疗这些疾病的孤儿产品的血红素制剂存在一些缺点，包括化学稳定性差，保质期短，以及令人烦恼的副作用，如凝血功能异常和静脉输液部位的静脉炎。这些特点限制了血红素治疗在美国门静脉症患者中的应用。因此，血红素精氨酸的可用性对这些疾病患者来说将是一个明显的优势。这些研究的目的是：1)从缓解症状和降低卟啉前体水平的角度，考察血红素精氨酸在改善症状和降低卟啉前体水平方面的安全性和有效性；2)研究血红素精氨酸输注对预防多发性卟啉发作的价值；3)开展剂量范围的研究，探讨血红素精氨酸对稳定的急性间歇性卟啉病患者降低卟啉前体水平的作用。这些多中心研究的登记已经完成，正在与制造商合作分析数据，目的是支持血红素精氨酸在美国的许可。使用血红素疗法的预防方案的有效性首次得到证明。

The purpose of this project is to study heme arginate for the treatment of the acute porphyrias (acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria). Heme arginate (Normosang(R), Leiras) is a stable heme preparation for intravenous use that was developed and studied in Europe for acute porphyrias, but has not been available in the United States. The heme preparation currently approved by the FDA as an orphan product for the treatment of these disorders has a number of disadvantages, including poor chemical stability, a short shelf life and troublesome side effects such as coagulation abnormalities and phlebitis at the site of intravenous infusion. These features have limited the application of heme treatment in porphyria patients in the United States. Therefore, availability of heme arginate would be a distinct advantage to patients with these disorders. The aims of these studies are 1) to examine the safety and efficacy of heme arginate in patients with acute attacks of porphyria in terms of producing remissions of symptoms and lowering porphyrin precursors; 2) to study the value of heme arginate infusions for the prevention of frequently occurring attacks of porphyria; 3) to carry out dose-ranging studies of effects of heme arginate on reducing porphyrin precursor levels in stable patients with acute intermittent porphyria. Enrollment in these multicenter studies has been completed and data is being analyzed in cooperation with the manufacturer with the aim of supporting the licensing of heme arginate in the U.S. The efficacy of a preventive regimen using heme therapy has been demonstrated for the first time.