美国食品和药物管理局（FDA）近日授予Celator Pharma公司纳米尺度抗癌药Vyxeos（又名CPX-351）突破性药物资格，该药开发用于急性髓性白血病（AML）及其他血液癌症的治疗。具体而言，FDA已授予Vyxeos用于治疗相关急性髓性白血病（therapy related AML，t-AML）和伴有骨髓增生异常变化的AML（AML-MRC）成人患者的突破性药物资格。
Vyxeos是一种以5：1比例配比的标准癌症药物阿糖胞苷（cytarabine）和柔红霉素（daunorubicin）组合疗法，2种药物封装在一个纳米尺度的递送载体。Celator公司表示，这种纳米递送载体可增强疗效，同时限制了单独服用每种药物的风险。
FDA授予Vyxeos突破性药物资格，主要基于一项关键性III期临床试验的强劲疗效数据。该研究在既往未接受治疗的（初治）高危AML年老患者中开展，数据显示，与标准的阿糖胞苷+柔红霉素（7+3）疗法相比，Vyxeos治疗使总生存期（OS）实现了统计学意义的显著改善，达到了研究的主要终点。研究中，Vyxeos治疗组中位生存时间为9.56个月，对照组（7+3）为5.95个月。此外，与对照组（7+3）相比，Vyxeos治疗组死亡风险降低31%，缓解率也具有统计学意义的显著改善。Vyxeos治疗组患者1年存活率达41.5%，2年存活率达31.3%，而对照组（7+3）1年存活率为27.6%、2年存活率为12.3%。Vyxeos治疗组60天全因死亡率为13.7%，对照组为21.2%。相关数据将在6月4日举行的2016年美国临床肿瘤学会（ASCO）年会上公布。
基于该项研究的强效数据，Celator公司表示，将于今年第三季度向FDA提交Vyxeos的新药申请（NDA）。Celator是一家致力于肿瘤治疗的生物制药公司，该公司专有的技术平台CombiPlex能够合理设计并快速评价抗癌药物的组合，结合传统化疗与分子靶向药物，提供更强的抗肿瘤活性。CombiPlex通过体外识别组合药物的最有效协同摩尔比，同时在一种纳米尺度的药物递送复合物中固定这种摩尔比，使其在给药后能够维持这种优化的组合，确保这种摩尔比暴露于肿瘤组织，这种技术平台可解决常规组合方案的多个根本性弊端，以及组合药物开发所面临的固有挑战。
Vyxeos是Celator公司的先导化合物，这是一种纳米尺度的阿糖胞苷+柔红霉素制剂，目前已完成治疗急性髓性白血病（AML）的一项III期临床。此外，该公司也有几个药物处于临床开发：CPX-1，这是一种伊立替康+氟脲苷纳米脂质体制剂，目前处于I期临床治疗结直肠癌；CPX-8，一种疏水性的泰索帝纳米制剂，处于临床前阶段。最近，该公司扩大了CombiPlex平台的应用，纳入了分子靶向疗法。
Vyxeos™ Improves Survival for Elderly in AML
Results from a recent phase III clinical trial have demonstrated an improved survival benefit with the use of Vyxeos (CPX-351) compared with the standard chemotherapy combination consisting of cytarabine and daunorubicin (7+3). These results will be submitted for presentation at the upcoming 2016 annual meeting of the American Society of Clinical Oncology (ASCO).
Acute myeloid leukemia (AML) is diagnosed in approximately 20,000 individuals each year in the United States. It is an aggressive leukemia, with the lowest survival rates of any acute leukemias.
AML prevents certain immune cells from developing properly, leaving them in immature stages. These cancerous cells, referred to as “blasts”, are not able to fight infection as intended, and rapidly accumulate in the body. This crowds out other blood cells so that they are not able to carry out their essential functions.
The cornerstone of standard therapy for AML is chemotherapy, and has remained essentially unchanged in the past 25 years, demonstrating a clear need for novel strategies.
One commonly used treatment for the elderly in AML includes the combination of the chemotherapy agents, cytarabine and daunorubicin. This combination is referred to as 7+3 in reference of the ratios of the drugs used together.
However, researchers recently demonstrated that a ratio of 5 to 1, with the same chemotherapy agents, provides improved anti-cancer effects compared to the standard ratio.
Vyxeos is a drug that is in the last phases of clinical trials prior to the submission of approval to the United States Food and Drug Administration (FDA). It is comprised of cytarabine and daunorubicin in the 5 to 1 ratio.
A phase III clinical trial was recently conducted to directly compare Vyxeos to the standard 7+3 combination of cytarabine plus daunorubicin for elderly patients with AML who were at a high risk of developing a disease recurrence. In the trial, one group of patients was treated with Vyxeos, and a second group was treated with the standard 7+3 combination. Results were directly compared between the two groups of patients.
•Median overall survival was improved by 3.6 months for patients treated with Vyxeos (nearly 10 months), compared to those treated with 7+3 (nearly 6 months).
•12 months following initiation of treatment, 41.5% of patients treated with Vyxeos were still alive, compared with only 27.6% of patients treated with 7+3.
•24 months following initiation of treatment, 31.1% of patients treated with Vyxeos were still alive, compared with only 12.3% treated with 7+3.
•The rate of serious side effects was comparable between the two treatment groups.
Based on these results, a new drug application (NDA) is expected to be submitted to the FDA later this year.
According to a press release announcing these results, Jeffrey E. Lancet, M.D., senior member and chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center and the principal investigator for the study stated that “The overall survival advantage seen with CPX-351 compared to 7+3, along with a superior response rate and no increase in serious toxicity indicates that we’ll likely have a new standard of care for treating older patients with secondary AML. This represents a major step forward for a very difficult-to-treat patient population.” |
