HEME ARGINATE IN ACUTE PORPHYRIA

本研究旨在探讨血红素精氨酸治疗急性卟啉症（急性间歇性卟啉症、斑状卟啉症、遗传性粪卟啉症）的疗效。 精氨酸血红素（Normosang（R），Leiras）是一种稳定的血红素制剂，用于静脉注射，在欧洲开发和研究用于急性卟啉症，但在美国尚未上市。 目前被FDA批准为用于治疗这些疾病的孤儿产品的血红素制剂具有许多缺点，包括化学稳定性差、保质期短和麻烦的副作用，例如静脉内输注部位的凝血异常和静脉炎。 这些特征限制了血红素治疗在美国卟啉病患者中的应用。因此，血红素精氨酸的可用性将是一个明显的优势，这些疾病的患者。 这些研究的目的是：1）检查血红素精氨酸盐在缓解症状和降低卟啉前体方面对卟啉病急性发作患者的安全性和有效性; 2）研究血红素精氨酸盐输注对预防频繁发生的卟啉病发作的价值; 3）开展血红素精氨酸盐降低急性间歇性卟啉病稳定期患者卟啉前体水平的剂量范围研究。这些多中心研究的入组已经完成，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。首次证明了使用血红素治疗的预防方案的有效性。

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.