诺华3月7日宣布，有关Jakavi（ruxilitinib）的一项关键性III期RESPONSE研究，达到了维持红细胞压积（红细胞体积）受控而无需放血（phlebotomy，从身体中出去一些血液的一种程序，以减少红细胞浓度）的主要终点，同时降低了对羟基脲有抵抗或不耐受真性红细胞增多症患者脾脏大小，研究中ruxolitinib的安全性与以往研究一致。
该项研究的数据将提交至即将召开的医学会议，并提交至全球各地的监管机构。
RESPONSE是一项全球性、随机、开放标签研究，在全球109个位点开展。试验中，222例对羟基脲有抗性或不耐受的真性红细胞增多症患者，随机接受ruxolitinib（10mg，每日2次）或最佳疗法（即研究人员选择的单药疗法或仅仅观察）。在整个研究中，剂量会随着需要进行调整。
该项研究的主要终点是，无需放血而血细胞比容得到控制的患者比例，以及32周时脾脏体积从基线缩小35%或更多（通过成像评估）。除安全性外，关键次要终点包括持久反应和完全的血液系统缓解。
红细胞增多症（polycythemia）是一种慢性、无法治愈的血液癌症，该病与血细胞生产过剩相关，导致血液增稠，血液凝块风险增加。这些血凝块可导致严重心血管并发症，如中风和心脏病发作，从而增加病发率和死亡率。红细胞增多症患者，常有脾脏肿大及额外衰弱的症状。许多患者经常规治疗后会变得不耐受或抵抗，这与病情恶化的风险升高有关。
关于
Jakavi（ruxolitinib）是一种口服JAK1和JAK2酪氨酸激酶抑制剂，于2012年8月获欧盟批准，用于治疗中级或高危骨髓纤维化，包括原发性骨髓纤维化，真性红细胞增多症后骨髓纤维化和原发性血小板增多症后骨髓纤维化。目前，Jakavi已获全球50多个国家批准，包括欧盟、加拿大和一些亚洲、拉丁美洲和南美洲国家。
诺华从Incyte公司授权获得ruxolitinib在美国以外的开发和商业化权利。欧盟委员会和FDA均已授予ruxolitinib治疗骨髓纤维化的孤儿药地位。目前，Incyte已经在美国以商品名Jakafi销售，用于中级或高危骨髓纤维化的治疗。
—Study of Jakavi (ruxolitinib) met primary endpoint, improving two key measures of disease control in patients with polycythemia vera
—Polycythemia vera is a chronic, incurable blood cancer with limited treatment options
—Ruxolitinib is the first selective JAK 1/2 inhibitor to demonstrate efficacy in a Phase III trial for treating polycythemia vera
—Data will be presented at an upcoming medical congress and submitted to worldwide regulatory authorities this year
Basel, March 7, 2014 - Novartis today announced that a pivotal Phase III trial of Jakavi? (ruxolitinib) compared to best available therapy has met its primary endpoint of maintaining hematocrit control (red blood cell volume) without the need for phlebotomy (a procedure to remove blood from the body to reduce the concentration of red blood cells[1]) and reducing spleen size in patients with polycythemia vera resistant to or intolerant of hydroxyurea. The safety profile of ruxolitinib was generally consistent with previous studies based on initial review of the data.
Data from the study (RESPONSE) will be presented at an upcoming medical congress and submitted to worldwide regulatory authorities this year.
"We are encouraged by these pivotal Phase III trial results, which show the potential of ruxolitinib to help patients with polycythemia vera," said Alessandro Riva, President, Novartis Oncology ad interim and Global Head, Oncology Development and Medical Affairs. "We plan to submit these data to worldwide regulatory agencies this year, as we seek to bring ruxolitinib to patients with polycythemia vera who are no longer responding to or are intolerant of prior therapy."
Polycythemia vera is a chronic, incurable blood cancer associated with an overproduction of blood cells. This leads to a thickening of the blood and increased risk of blood clots[1]. These clots can cause serious cardiovascular complications, such as stroke and heart attack, resulting in increased morbidity and mortality. Patients with polycythemia vera often have enlarged spleen and additional debilitating symptoms[1]. Many patients treated with commonly available therapies become intolerant or resistant, which is associated with an increased of risk of progression[3],[4].
RESPONSE is a global, randomized, open-label study conducted at 109 sites. The trial randomized 222 patients with polycythemia vera resistant to or intolerant of hydroxyurea. Patients were randomized 1:1 to receive either ruxolitinib (10 mg twice-daily) or best available therapy, which was defined as investigator selected monotherapy or observation only. The dose was adjusted as needed throughout the study.
The primary endpoint of the study is the proportion of patients whose hematocrit is controlled without phlebotomy and whose spleen volume is reduced by 35% or more from baseline as assessed by imaging at 32 weeks. In addition to safety, key secondary endpoints include durable response and complete hematological remission.
Ruxolitinibis currently approved in more than 55 countries for patients with myelofibrosis, a debilitating and life-threatening blood cancer.
About Jakavi
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases and was approved by the European Commission in August 2012 for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. Jakavi is approved in more than 55 countries, including the European union, Canada and some countries in Asia, Latin and South America. Additional worldwide regulatory filings are underway.
Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States. Both the European Commission and the U.S. Food and Drug Administration (FDA) granted ruxolitinib orphan drug status for myelofibrosis. Jakavi is marketed in the United States by Incyte Corporation under the name Jakafi? for the treatment of patients with intermediate or high-risk myelofibrosis.
The recommended starting dose for Jakavi in patients with myelofibrosis is 15 mg twice daily for patients with a platelet count between 100,000cubic millimeters (mm3) and 200,000 mm3,and 20 mg twice daily for patients with a platelet count of >200,000 mm3. Doses may be titrated based on safety and efficacy. There is limited information to recommend a starting dose for patients with platelet counts between 50,000/mm3 and <100,000/mm3. The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously[5].
Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation.
The safety and efficacy profile of Jakavi has not yet been established outside the approved indication.
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