Background

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown.

Methods

Download a PDF of the Research Summary.

In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms).

Results

Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P=0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common.

Conclusions

In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040. opens in new tab.)

QUICK TAKE VIDEO SUMMARY
Rusfertide for Control of Erythrocytosis in Polycythemia Vera
 02:37

中文翻译：

---

Rusfertide，一种铁调素模拟物，用于控制真性红细胞增多症的红细胞增多

背景

真性红细胞增多症是一种以红细胞增多为特征的慢性骨髓增生性肿瘤。Rusfertide 是一种主要铁调节激素铁调素的注射肽模拟物，限制红细胞生成中铁的可用性。rusfertide 在静脉切开术依赖性真性红细胞增多症患者中的安全性和有效性尚不清楚。

方法

下载研究摘要的 PDF 版本。

在国际 2 期 REVIVE 试验的第 1 部分中，我们招募了患者进行为期 28 周的 rusfertide 剂量探索评估。第 2 部分是双盲、随机停药期，其中我们以 1:1 的比例分配患者接受 rusfertide 或安慰剂治疗，为期 12 周。主要疗效终点是缓解，定义为血细胞比容控制、不进行静脉切开术以及第 2 部分期间试验方案的完成。患者报告的结果通过改良版骨髓增生性肿瘤症状评估表 (MPN-SAF) 进行评估日记（分数范围从 0 到 10，分数越高表明症状越严重）。

结果

70 名患者参加了试验的第 1 部分，59 名患者在第 2 部分中被分配接受 rusfertide（30 名患者）或安慰剂（29 名患者）。在试验期间，每年静脉切开术的估计平均数 (±SD) 为 8.7±2.9 例。第一次服用 rusfertide 前 28 周，第 1 部分期间为 0.6±1.0（估计差异，每年 8.1 次静脉切开术）。第 1 部分期间的平均最大血细胞比容为 44.5±2.2%，而首次服用 rusfertide 前 28 周期间的平均最大血细胞比容为 50.0±5.8%。在第 2 部分中，接受 rusfertide 治疗的患者中有 60% 出现缓解，而接受安慰剂治疗的患者只有 17% 有缓解（P=0.002）。在基线和第 1 部分结束之间，rusfertide 治疗与基线时有中度或重度症状的患者 MPN-SAF 上的个体症状评分下降相关。在第 1 部分和第 2 部分期间，13% 的患者发生 3 级不良事件，没有患者发生 4 级或 5 级事件。严重程度为 1 级或 2 级的注射部位反应很常见。

结论

在真性红细胞增多症患者中，在 28 周剂量探索期间，rusfertide 治疗的平均血细胞比容低于 45%，并且在 12 周随机停药期期间出现反应的患者百分比高于 rusfertide与安慰剂。（由 Protagonist Therapeutics 资助；REVIVE ClinicalTrials.gov 编号，NCT04057040 。在新选项卡中打开。）

快速视频摘要
Rusfertide 用于控制真性红细胞增多症中的红细胞增多
 02:37