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美国食品与药物管理局（FDA）批准Jakafi(ruxolitinib)上市，这是第一个获准的专门治疗骨髓纤维化的药物。 骨髓纤维化是骨髓被瘢痕组织替换，导致血细胞在肝脏和脾脏生成，该病的特征是脾肿大、贫血、白细胞和血小板减少，以及骨髓纤维化的相关症状，包括乏力、腹部不适、肋骨下疼痛、肌肉骨骼疼痛、瘙痒和盗汗。 Jakafi（每次1片，每日2次）抑制JAK 1和JAK2酶（Janus相关激酶），该酶涉及调节血液和免疫功能。骨髓纤维化与JAK 1和JAK2失调相关。 美国FDA药物研究与评价中心血液和肿瘤产品办公室主任理查（Richard Pazdur）说：“Jakafi代表了肿瘤学领域一种日渐增多的趋势，即通过对疾病机制详细的科学理解，研发出针对特殊分子通路的药物。促使该药获准的临床试验，主要关注了骨髓纤维化病人常有的脾肿大和疼痛。” 两项纳入528例病人的临床试验，评价了Jakafi的安全性和有效性。参加两项试验的病人都对现有骨髓纤维化疗法耐药或治疗无效，或不适合骨髓移植治疗。所有病人均有脾肿大。 病人被选择接受Jakafi、安慰剂或现有的最好治疗（化疗药羟基脲或糖皮质激素）。与其他两组相比，Jakafi组脾脏缩小35%以上病人的比例更大。同样，与安慰剂组相比，Jakafi组骨髓纤维化症状减少50%以上的病人比例更大，这些症状包括腹部不适、盗汗、瘙痒、骨骼或肌肉痛等。 Jakafi最严重的副作用包括血小板减少、贫血、乏力、腹泻、气短、头痛、头晕和恶心。Jakafi通过FDA的优先审查程序获准。 美国初始批准：2011 一般描述 化学名(R)-3-(4-(7H-pyrrolo[2,3d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile phosphate。 分子量404.36。 Ruxolitinib磷酸盐有下列结构式：
作用机制 Ruxolitinib，一种激酶抑制剂, 抑制Janus相关激酶(JAKs)JAK1和JAK2，介导对造血和免疫功能重要的若干细胞因子和生长因子信号。JAK信号涉及细胞因子受体对 STATs(信号转导物和转炉激活的补充，激活和随后STATs定位至细胞核导致基因表达的调控。 适应证和用途 Jakafi是一种激酶抑制剂适用于治疗中间或高危骨髓纤维化, 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患者. 剂量和给药方法 剂型和规格 片：5 mg，10 mg，15 mg，20 mg和25 mg。 禁忌证 警告和注意事项 不良反应 药物相互作用 特殊人群中使用 INLYTA片供应如下： 1 mg片是红色膜衣，椭圆片一侧凹有“Pfizer”和另一侧“1 XNB”；得到80片瓶: NDC 0069-0145-01。
Jakafi™ (ruxolitinib) FDA Approves Incyte’s Jakafi™ (ruxolitinib) for Patients with Myelofibrosis Signs and symptoms of the disease, in which the bone marrow is replaced by scar tissue resulting in blood cells being made in organs such as the liver and the spleen, are an enlarged spleen, anemia, decreased white blood cells and platelets, fatigue, abdominal discomfort, pain under the ribs, feelings of satiety, muscle and bone pain, itching, and night sweats. Jakafi, made by Incyte Corp. is a pill taken two times a day, inhibits JAK 1 and 2 (Janus Associated Kinase), which are involved in regulating blood and immunological functioning. Myelofibrosis is associated with the deregulation of JAK 1 and 2. “Jakafi represents another example of an increasing trend in oncology where a detailed scientific understanding of the mechanisms of a disease allows a drug to be directed toward specific molecular pathways,” Richard Pazdur, MD, Director of the FDA’s Office of Hematology and Oncology Products in the Center for Drug Evaluation and Research, said in a statement. “The clinical trials leading to this approval focused on problems that patients with myelofibrosis commonly encounter, including enlarged spleens and pain.” “Today’s FDA approval of Jakafi has the potential to transform the way we treat myelofibrosis,” said Srdan Verstovsek, MD, PhD, Associate Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center, the principal investigator of the COMFORT-I pivotal trial. “In this Phase III clinical trial, we observed significant reductions in spleen size and significant improvements in symptoms. Importantly, these benefits were achieved early on, most within a month, and tended to be durable during treatment. In contrast, most of the patients who received placebo saw their spleens increase and their symptoms worsen.” The safety and effectiveness of Jakafi was evaluated in two clinical trials with 528 patients. Patients in both trials were resistant or refractory to available myelofibrosis therapy or ineligible for allogeneic bone marrow transplantation. All patients had splenomegaly and were in need of treatment as a result of disease-related symptoms. Patients in the studies were selected to receive treatment with either Jakafi, placebo, or the best available therapy (hydroxyurea or glucocorticoids). A greater percentage of patients receiving Jakafi experienced more than a 35% reduction in spleen size when compared with patients receiving placebo or best available therapy. Similarly, more patients receiving Jakafi had more than a 50% reduction in their myelofibrosis-related symptoms than was the case in patients receiving placebo. |
