Department of Clinical Sciences and Community, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Policlinico Hospital, University of Milan, Milan, Italy; and.
Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Blood Adv. 2021 Jan 12;5(1):326-333. doi: 10.1182/bloodadvances.2020002725.
Luspatercept is an activin receptor ligand trap that has been shown to enhance late-stage erythropoiesis in animal models of β-thalassemia. A multicenter, international, phase 2 dose-finding study was initiated in adult patients with β-thalassemia, either non-transfusion-dependent thalassemia (NTDT) or transfusion-dependent thalassemia (TDT). Positive results of the phase 2 study paved the way to a randomized phase 3 clinical trial (BELIEVE) to assess the efficacy and safety of luspatercept. The BELIEVE trial is a randomized, double-blind, placebo-controlled phase 3 trial. Three hundred thirty-six patients aged ≥18 years with TDT (regularly transfused, 6-20 red blood cell units within 24 weeks before randomization) were included in the trial. Patients received luspatercept or placebo subcutaneously every 21 days for ≥48 weeks and best supportive care. Forty-eight of 224 patients (21.4%) in the luspatercept group achieved the primary end points (≥33% reduction in transfusion burden) compared with those in the placebo group (4.5%; P < .001). Moreover, more patients had a ≥33% reduction in transfusion burden during any rolling 12-week interval (70.5% vs 29.5%) or any 24-week interval (41.1% vs 2.7%) with luspatercept than with the placebo. Transfusion independence was achieved by 11% of patients in the luspatercept group. Transient adverse events were more frequent with luspatercept than with placebo, but were manageable. Luspatercept was approved by the US Food and Drug Administration in 2019 and by the European Medicines Agency in 2020. The luspatercept trial is registered on www.clinicaltrials.gov at #NCT01749540 and the BELIEVE trial at #NCT02604433.
芦帕他赛是一种激活素受体配体陷阱，已被证明可增强β-地中海贫血动物模型中的晚期红细胞生成。一项多中心、国际性的 2 期剂量发现研究在非输血依赖型地中海贫血（NTDT）或输血依赖型地中海贫血（TDT）的成年患者中启动。2 期研究的阳性结果为评估芦帕他赛的疗效和安全性的随机 3 期临床试验（BELIEVE）铺平了道路。BELIEVE 试验是一项随机、双盲、安慰剂对照的 3 期试验。336 名年龄≥18 岁的 TDT 患者（在随机分组前 24 周内定期输血，6-20 个红细胞单位）纳入该试验。患者接受芦帕他赛或安慰剂皮下注射，每 21 天一次，持续≥48 周，并接受最佳支持治疗。与安慰剂组（4.5%；P<.001）相比，芦帕他赛组有 48/224 名患者（21.4%）达到主要终点（输血负担减少≥33%）。此外，在任何滚动 12 周间隔（70.5%比 29.5%）或任何 24 周间隔（41.1%比 2.7%）内，更多患者的输血负担减少≥33%。芦帕他赛组有 11%的患者实现了输血独立性。与安慰剂相比，芦帕他赛更常发生短暂的不良反应，但可管理。芦帕他赛于 2019 年获得美国食品和药物管理局批准，2020 年获得欧洲药品管理局批准。芦帕他赛试验在 www.clinicaltrials.gov 上注册，编号为#NCT01749540，BELIEVE 试验编号为#NCT02604433。
