Global Blood Therapeutics (GBT) reported new data from its Phase III HOPE trial of voxelotor in sickle cell disease (SCD). The drug met the primary endpoint, improvement in hemoglobin greater than 1 g/dL at 24 weeks, in 274 patients ages 12 and older with the disease.
The HOPE trial involved 274 patients with SCD from 60 institutions across 12 countries. The research has also been published in The New England Journal of Medicine and will be presented today at the Presidential Symposium at the 24th European Hematology Association (EHA) Congress in Amsterdam.
“These additional data from our multi-national, Phase III HOPE Study support and strengthen the 24-week findings from 154 patients that were presented at the American Society of Hematology Annual Meeting in December 2018,” stated Ted W. Love, president and chief executive officer of BGT. “These updated results from the basis of the rolling submission of our New Drug Application for voxelotor, which we are on track to complete in the second half of this year for review under an accelerated approval pathway.”
SCD is a lifelong inherited blood disease, the result of a mutation in the beta-chain of hemoglobin. This results in hemoglobin, which is a protein inside red blood cells that carries oxygen throughout the body, forming into stiff rods, which changes the shape of the red blood cells. That shape is the distinct crescent or sickle shape that gives the disease its name. The change in the red blood cells decreases the lifespan of the red blood cells from about 10 to 20 days instead of the normal 90 to 120 days, resulting in anemia.
Voxelotor is an oral, once-daily treatment for SCD that works by increasing hemoglobin’s affinity for oxygen. The drug appears to block polymerization, which causes the sickling and destruction of red blood cells.
The U.S. Food and Drug Administration (FDA) granted the drug Breakthrough Therapy, Fast Track, Orphan Drug and Rare Pediatric Disease designations for SCD. The European Medicines Agency (EMA) included the drug in its Priority Medicines (PRIME) program and the European Commission (EC) has also included it in its Priority Medicines (PRIME) program and designated it an orphan drug.
In the trial, hemoglobin improved quickly from baseline to 2 weeks, which was the earliest measurement point. This was sustained through 24 weeks compared to placebo. There were also numerically fewer vaso-occlusive crises (VOCs), which are a common complication of SCD. They are incidents of severe pain that often require emergency room visits.
“These positive data from more than 270 patients enrolled in the HOPE Study provide strong evidence that voxelotor, by significantly improving anemia and hemolysis, has the potential to be a disease-modifying treatment for SCD by preventing chronic organ damage and prolonging survival,” stated Jo Howard, a HOPE Study investigator and hematologist with Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London. “Given the observed ability of voxelotor to reduce anemia, hemolysis and red blood cell sickling, as well as a favorable safety profile, I am confident that voxelotor could potentially become a new standard-of-care for treating adolescents and adults with SCD.”
全球血液疗法（ GBT ）报告了新的数据从其第三期 HOPE 试验的体素镰状细胞病（ SCD ）。该药物达到了主要终点，24周时血红蛋白的改善大于1g / dL ，在274名12岁以上患有这种疾病的患者中。
HOPE 试验涉及来自12个国家60个机构的274名 SCD 患者。这项研究也发表在《新英格兰医学杂志》上，并将于今天在阿姆斯特丹第24届欧洲血液学协会（ EHA ）大会的总统研讨会上发表。
BGT 总裁兼首席执行官 Ted W . Love 表示：“我们的多国第三阶段 HOPE 研究提供的这些额外数据支持并加强了在2018年12月美国血液学会年会上公布的154名患者的24周发现。”“这些更新的结果是基于我们的新药物紫杉醇申请的滚动提交，我们将在今年下半年完成审查，在加速审批途径。”
紫杉醇是一种口服的，每天一次的 SCD 治疗，通过增加血红蛋白对氧的亲和力发挥作用。这种药物似乎阻止了聚合，导致红细胞的镰状和破坏。
美国食品药品监督管理局（Food and Drug Administration）（ FDA ）授予 SCD 药物突破治疗、快速通道、孤儿药物和罕见儿科疾病的名称。欧洲药品管理局（ EMA ）将该药物列入其优先药品（ PRIME ）方案，欧洲委员会（ EC ）也将其列入其优先药品（ PRIME ）方案，并将其指定为孤儿药品。
在试验中，血红蛋白从基线快速提高到2周，这是最早的测量点。与安慰剂相比，这种情况持续了24周。血管闭塞性危机（ VOCs ）的数字也较少，这是 SCD 的常见并发症。他们是严重疼痛的事件，经常需要紧急的房间访问。
“来自参与 HOPE 研究的270多名患者的这些阳性数据提供了强有力的证据，表明紫杉醇通过显著改善贫血和溶血，有可能通过预防慢性器官损伤和延长生存期来改善 SCD 的疾病治疗。”一名 HOPE 研究研究员和血液学家，分别来自盖伊和圣乔治。托马斯的 NHS 基金会信托和伦敦国王学院.“鉴于所观察到的紫杉醇能够减少贫血、溶血和红细胞疾病，以及良好的安全状况，我相信紫杉醇有可能成为治疗青少年和成人 SCD 的新标准。”