HEME ARGINATE IN ACUTE PORPHYRIA

本项目旨在研究精氨酸血红素治疗急性卟啉症（急性间歇性卟啉症、多样性卟啉症和遗传性同比例卟啉症）的疗效。精氨酸血红素（Normosang(R), Leiras）是一种稳定的静脉使用血红素制剂，在欧洲开发和研究用于急性卟啉症，但尚未在美国上市。目前被FDA批准作为孤儿产品用于治疗这些疾病的血红素制剂有许多缺点，包括化学稳定性差，保质期短以及令人头疼的副作用，如凝血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卟啉症患者中的应用。因此，精氨酸血红素的可用性将是这些疾病患者的明显优势。这些研究的目的是：1)从产生症状缓解和降低卟啉前体的角度，检查精氨酸血红素在急性卟啉发作患者中的安全性和有效性；2)探讨精氨酸血红素输注预防频发卟啉发作的价值；3)开展精氨酸血红素对稳定型急性间歇性卟啉患者卟啉前体水平降低作用的剂量范围研究。这些多中心研究的登记已经完成，数据正在与制造商合作进行分析，目的是支持血红素精氨酸在美国的许可。使用血红素治疗的预防性方案的有效性已首次得到证实。

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.