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http://www.egeeker.com/thread-96-1-1.htmlOn May 14, 2014, AstraZeneca announced positive data from Phase I trial of its new lung cancer drug, known as AZD9291, showing AZD9291 shrank tumors in 51 percent of patients. Tumors shrank in 64 percent of patients found to have the mutation, known as T790M, which develops in about half of lung cancers that become resistant to drugs known as epidermal growth factor receptor (EGFR) inhibitors.
New promising data gave AstraZeneca, Britain's second-biggest drugmaker, fresh ammunition to argue that Pfizer's latest $106 billion takeover bid substantially undervalues the company. AstraZeneca believes it could sell as much as $3 billion a year, compared with ysts' estamate of $1 billion to $2 billion.
The Phase I trial for AZD9291, featured ahead of the American Society of Clinical Oncology (ASCO) 2014 annual meeting on May 30-June 3 in Chicago, involved 199 patients with advanced non-all cell lung cancer with EGFR mutations whose disease worsened despite treatment with a current EGFR drug.
AstraZeneca is currently conducting a Phase 2 study of AZD9291 in patients with the T790M mutation at a daily dose of 80 milligram, which it said could enable accelerated regulatory filing in the second half of next year.
AZD9291 has been granted “breakthrough” status by the U.S. Food and Drug Administration as a second-line therapy for non-all cell lung cancer. AstraZeneca will also study the drug as an initial treatment for eligible lung cancer patients. AZD9291 and CO-1686 from Clovis Oncology Inc are in a race to to bring a third-generation epidermal growth factor receptor (EGFR) inhibitor to market that targets the T790M non-all cell lung cancer (NSCLC).
AZD9291 is one of several new drugs flagged by AstraZeneca last week in a bid to convince investors of the strength of its experimental pipeline, which includes several innovative cancer drugs, as well as treatments for diabetes, asthma, rheumatoid arthritis and psoriasis. AstraZeneca has rejected a $106 billion approach from U.S. rival Pfizer, arguing that it has a bright independent future due to its promising line-up of new drugs. Pfizer is widely expected to return with a sweetened offer in coming days.
Sources:
Pasi A. Janne, et al., Clinical activity of the mutant-selective EGFR inhibitor AZD9291 in patients (pts) with EGFR inhibitor–resistant non-all cell lung cancer (NSCLC).. American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, May 30 – June 3, 2014, Time: Saturday May 31, 8:00 AM to 9:30 AM;Location: E Hall D1, Abstract 8009
Background: AZD9291 is a selective, third generation EGFR-TKI, effective against both EGFR-TKI sensitizing and resistance T790M mutations in preclinical models. We are conducting a phase I study of AZD9291 in EGFR mutant (EGFRm+) NSCLC pts
Conclusions: AZD9291 has robust efficacy and is well tolerated in EGFRm+ NSCLC pts with acquired resistance to EGFR-TKIs. Pts with EGFR T790M+ tumors have higher ORR with AZD9291 compared with those with EGFR T790M- tumors. Clinical trial information: NCT01802632.
阿斯利康肺癌新药AZD9291成功有望
阿斯利康这周三公布了其肺癌新药的临床数据，此药（AZD9291）为针对基因突变的靶向治疗药物，具有替代现有肿瘤治疗方案的潜力。在早期试验中AZD9291显示可使51%肺癌患者肿瘤缩小，并且发现肿瘤缩小的患者中有64%发生了T790M基因突变，约半数肺癌患者因为此基因突变而对表皮生长因子受体（EGFR）抑制剂类药物产生耐药性。EGFR抑制剂类药物如罗氏制药的特罗凯和埃罗替尼，常用于治疗各种突变性或高度活化型EGFR实体癌。非小细胞肺癌在肺癌中最为常见，而约15%的非小细胞肺癌患者在EGFR基因上产生了突变。
他们大多数终会成为EGFR抑制剂的耐受者，丹娜-法伯癌症研究所、波士顿哈佛医学院的医学教授以及这项研究的首席研究员帕斯·珍妮博士说。“近几十年中耐药性问题一直是化疗药物的克星” 美国临床肿瘤学会的主席侯选人彼特博士在一次新闻发布会上说，以往的研究使我们更好的理解了癌细胞的分子基础，现在可以将这些理论研究，应用于开发针对基因突变的靶向药物。AZD9291是阿斯利康为数不多的新药之一，作为公司的关键性药物使投资者确信其在新药开发上具有强劲实力，也是吸引辉瑞的主要因素。阿斯利康预测此抗癌药物的最高年销售额可达到30亿美元，而比目前分析师预测的10～20亿美元要高得多。
此药的I期试验数据将会在本月末的美国临床肿瘤学会(ASCO)年度会议上重点提出，这项研究涉及的199例受试者均为EGFR基因突变的晚期非小细胞肺癌患者，而现有的EGFR抑制剂治疗已不能控制其疾病恶化。该试验中最常见的副作用包括腹泻和皮疹，但研究者称其毒副作用低于现有的EGFR抑制剂。另外，阿斯利康正在进行AZN9291的II期研究，受试者为T790M突变者，每日给予80mg剂量。据悉，在明年下半年的申报中可获得快速审评资格。投资者急于看到阿斯利康公司在ASCO年会上提出其它癌症的试验数据。
公司的MEDI4736有潜力成为第一个抗PDL1的新型药物，可增强机体免疫系统而达到抗癌目的，它最初的试验设计是针对非小细胞肺癌的。阿斯利康预测MEDI4736的最高年销售额为65亿美元（包括联合用药），而分析师预测为20～70亿美元。阿斯利康发言人说会在本月末的ASCO年会上提交MEDI4736的试验更新数据。公司的另一个试验性药物（卵巢癌药物奥拉帕尼Olaparib）数据，也会在ASCO年会上作为会议最新摘要重点突出。阿斯利康预测其最高年销售额为20亿美元，而分析师一致预测为15～30亿美元。
