吉利德（Gilead）7月23日宣布，抗癌药Zydelig（idelalisib）获FDA批准，用于3种B细胞血癌的治疗，分别为：（1）批准Zydelig联合罗氏（Roche）抗癌药美罗华（Rituxan，通用名：rituximab，利妥昔单抗），用于适合Rituxan单药疗法的复发性慢性淋巴细胞白血病（CLL）患者的治疗；（2）批准Zydelig作为单药疗法，用于既往接受过至少2种系统治疗方案的复发性滤泡B细胞非霍奇金淋巴瘤（FL）患者和小细胞淋巴瘤（SLL）患者的治疗。FDA加速批准Zydelig用于FL和SLL适应症，是基于总缓解率（ORR）数据。
evaluatePharma分析师预计，到2020年，Zydelig的年销售额将突破12亿美元。而Bernstein分析师Geoff Porges则预计，到2017年，Zydelig的年销售额将突破15亿美元，使其当之无愧的成为吉利德后期管线中的一枚重磅明星药物。
Zydelig获批用于CLL，主要是基于一项关键III期研究（Study 116）的数据，该项研究在既往已接受治疗但对标准化疗不耐受的慢性淋巴细胞白血病（CLL）患者中开展。一项既定中期分析数据表明，与安慰剂+美罗华（Rituxan）治疗组相比，Zydelig+Rituxan治疗组在研究的主要终点—疾病无进展生存期（PFS）具有统计学意义的显著改善（PFS：10.7个月 vs 5.5个月，p＜0.0001）。此前，FDA已授予Zydelig治疗复发性CLL的突破性疗法认定。
Zydelig加速批准用于FL和SLL，基于一项关键II期研究（Study 101-09）的数据，该项研究在既往经美罗华（Rituxan）和含烷化剂化疗方案治疗的难治性惰性非霍奇金淋巴瘤（iNHL，注：FL和SLL是2种类型的iNHL）患者中开展，评价了Zydelig的疗效和安全性。研究结果表明，Zydelig单药疗法取得了57%的总缓解率（ORR），其中，6%的患者实现了完全缓解，50%的患者实现部分缓解，1%的患者取得轻微缓解。研究中，平均缓解持续时间达12.5个月，距离缓解的平均时长为1.9个月，平均无进展生存期为11.0个月，平均总生存期为20.3个月，90%的患者经历了淋巴结的缩小。
Zydelig（idelalisib）是一种首创的高度选择性、口服有效的磷酸肌醇3-激酶delta（PI3K-delta）抑制剂。PI3K-delta信号对于B淋巴细胞的活化、增殖、生存、迁移（trafficking）至关重要，该信号在多种B细胞恶性肿瘤中过度活动。目前，吉利德正开发idelalisib作为单一制剂，以及与一些已获批的疗法和实验性疗法配伍，调查用于不同类型血癌的治疗。
英文原文：U.S. Food and Drug Administration Approves Gilead's Zydelig® (idelalisib) for Relapsed Chronic Lymphocytic Leukemia, Follicular Lymphoma and Small Lymphocytic Lymphoma
-- 82 Percent Reduction in Risk of Disease Progression or Death When Combined with Rituximab Compared to Rituximab Alone in Patients with Relapsed Chronic Lymphocytic Leukemia --
FOSTER CITY, Calif.--Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved Zydelig® (idelalisib) 150 mg tablets for the treatment of three B-cell blood cancers. Zydelig is indicated in combination with rituximab for patients with relapsed chronic lymphocytic leukemia (CLL) for whom rituximab alone would be considered appropriate therapy and as monotherapy for patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) and small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies. Accelerated approval was granted for FL and SLL based on overall response rate. Zydelig is a first-in-class inhibitor of PI3K delta, a protein that is over-expressed in many B-cell malignancies and plays a role in the viability, proliferation and migration of these cancer cells.
"Zydelig is a much needed new treatment option for appropriate patients with CLL and these indolent lymphomas who have experienced relapses and have limited, if any, treatment options," said Bruce Cheson, MD, Professor of Medicine, Head of Hematology and Director of Hematology Research at Lombardi Comprehensive Cancer Center at Georgetown University, and a principal investigator on the Zydelig pivotal Phase 3 trial in CLL. "In clinical studies among patients with relapsed CLL, FL and SLL, Zydelig produced strong responses, including a significant improvement in progression-free survival in CLL. I believe it helps fill a significant unmet need for these patients."
Over 200,000 Americans are living with CLL, FL or SLL, slow-growing incurable blood cancers that can lead to life-threatening complications such as anemia, serious infection and bone marrow failure requiring treatment. Relapse commonly occurs after initial chemoimmunotherapy and many patients with relapsed CLL, FL or SLL are unable to tolerate chemotherapy, which may limit their treatment options.
"Gilead is committed to the development of novel cancer therapies and we are proud to have this opportunity to make a difference in the lives of people living with these cancers," said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. "We extend our thanks to the many physicians and patients who participated in Zydelig clinical trials, and are now focused on making this medicine available to patients as expeditiously as possible."
The product's approval in CLL is supported primarily by data from a randomized, placebo-controlled Phase 3 trial (Study 116) of Zydelig plus rituximab in 220 patients with relapsed CLL who were not able to tolerate standard chemotherapy. Study 116 was stopped early in October 2013 by an independent Data Monitoring Committee due to a highly statistically significant benefit in progression-free survival (PFS) in the Zydelig arm as compared to those receiving rituximab alone (hazard ratio = 0.18 (95 percent CI: 0.10, 0.32), p<0.0001). Median PFS was not reached in the Zydelig plus rituximab arm (95 percent CI: 10.7 months, NR) and was 5.5 months in the placebo plus rituximab arm (95 percent CI: 3.8, 7.1). The FDA granted Zydelig a Breakthrough Therapy designation for relapsed CLL, a designation granted to drug candidates that may offer major advances in treatment over existing options.
Zydelig's accelerated approval in FL and SLL, two types of indolent non-Hodgkin lymphoma, is supported by data from a single-arm Phase 2 study (Study 101-09) of Zydelig monotherapy in patients refractory to rituximab and alkylating-agent-containing chemotherapy (FL: n=72; SLL: n=26). In the study, Zydelig achieved an overall response rate of 54 percent (range: 42-66 percent) and 58 percent (range: 37-77 percent), respectively, in FL and SLL patients. Of the responses seen in FL patients, 8 percent (n=6) were complete responses; all 15 responses in SLL patients were partial responses. The median duration of response was 11.9 months in SLL patients (range: 0.0, 14.7 months) and median duration of response was not reached in FL patients (range: 0.0, 14.8 months). Improvement in patient survival or disease related symptoms has not been established in these indications. Results of Study 116 and Study 101-09 were published in The New England Journal of Medicine in March 2014.
Zydelig has a BOXED WARNING in its product label regarding the risks of fatal and serious toxicities: hepatic, severe diarrhea, colitis, pneumonitis and intestinal perforation; see below for important Safety Information, including contraindications and warnings and precautions.
FDA has also approved a risk evaluation and mitigation strategy (REMS) for Zydelig. The purpose of the Zydelig REMS is to inform healthcare providers of the serious risks of hepatotoxicity, severe diarrhea, colitis, pneumonitis and intestinal perforation. Additional information about the Zydelig REMS program can be found at www.ZydeligREMS.com.
The most common adverse reactions (incidence ≥20 percent; all grades) in patients given Zydelig with or without rituximab are diarrhea, pyrexia, fatigue, nausea, cough, abdominal pain, chills and rash. The most common lab abnormalities (incidence ≥30 percent; all grades) in clinical studies were neutropenia, hypertriglyceridemia, hyperglycemia and ALT/AST elevations (indicators of liver function).
U.S. Patient Support Program
Gilead is committed to ensuring that patients with CLL, FL and SLL can access Zydelig and has launched Zydelig AccessConnect™ to provide assistance to appropriate patients who are uninsured, underinsured or who need financial assistance to pay for the medicine. The program consists of an integrated offering of support services for patients and providers, including:
Access to dedicated case specialists to help patients and their providers with insurance-related needs, including identifying coverage options.
The Zydelig Co-pay Coupon Program, which provides co-pay assistance for eligible patients with private insurance who need assistance paying for out-of-pocket medication costs. Most patients will pay no more than $5 per monthly co-pay.
Gilead will provide support to independent non-profit organizations that provide assistance for eligible federally-insured and privately-insured patients who need help covering out-of-pocket medication costs.
Eligible patients who have been prescribed Zydelig for an FDA-approved indication and who are experiencing insurance coverage delays greater than five business days may receive a 30-day supply of Zydelig while coverage is established.
Patients enrolled into Zydelig AccessConnect will receive the support needed to connect with a specialty pharmacy based on the policies of their individual health plan.
The AccessConnect Patient Assistance Program will provide Zydelig at no charge for eligible patients with no other insurance options.
Information about how to apply for any of these forms of assistance, and more information on authorized distributors and specialty pharmacies can be found at www.zydeligaccessconnect.com or by calling 1-844-6ACCESS (1-844-622-2377) between 8 a.m. and 8 p.m. ET.
about Zydelig (idelalisib)
Zydelig is an oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, a protein that plays a role in the activation, proliferation and viability of B cells, a critical component of the immune system. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and by inhibiting the protein, Zydelig blocks several cellular signaling pathways that drive B-cell viability. Zydelig is indicated in combination with rituximab for the treatment of relapsed chronic lymphocytic leukemia in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities and as monotherapy for relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior therapies. The FL and SLL indications were granted accelerated approval based on overall response rate; improvement in patient survival or disease related symptoms has not been established in these indications. Continued approval for these indications is contingent upon verification of clinical benefit in confirmatory trials. Zydelig is available as 150 mg and 100 mg tablets, administered orally twice-daily; 150 mg is the recommended starting dose (see important Safety Information below for dose modification instructions).
important Safety Information
BOXED WARNING: FATAL and SERIOUS TOXICITIES: HEPATIC, SEVERE DIARRHEA, COLITIS, PNEUMonITIS and INTESTINAL PERFORATION
Fatal and/or serious hepatotoxicity occurred in 14 percent of Zydelig-treated patients. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue Zydelig as recommended.
Fatal, serious, and/or severe diarrhea or colitis occurred in 14 percent of Zydelig-treated patients. Monitor for the development of severe diarrhea or colitis. Interrupt and then reduce or discontinue Zydelig as recommended.
Fatal and serious pneumonitis can occur. Monitor for pulmonary symptoms and bilateral interstitial infiltrates. Interrupt or discontinue Zydelig as recommended.
Fatal and serious intestinal perforation can occur in Zydelig-treated patients. Discontinue Zydelig for intestinal perforation.
Contraindications
History of serious allergic reactions, including anaphylaxis and toxic epidermal necrolysis (TEN)
Warnings and Precautions
Hepatotoxicity: Findings were generally observed within the first 12 weeks of treatment and reversed with dose interruption. Upon rechallenge at a lower dose, ALT/AST elevations recurred in 26 percent of patients. In all patients, monitor ALT/AST every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, and every 1 to 3 months thereafter. If ALT/AST is >3x upper limit of normal (ULN), monitor for liver toxicity weekly. If ALT/AST is >5x ULN, withhold Zydelig and monitor ALT/AST and total bilirubin weekly until resolved. Discontinue Zydelig for recurrent hepatotoxicity. Avoid concurrent use with other hepatotoxic drugs.
Severe diarrhea or colitis: Grade 3+ diarrhea can occur at any time and responds poorly to antimotility agents. Avoid concurrent use with other drugs that cause diarrhea.
Pneumonitis: evaluate for pneumonitis in patients presenting with pulmonary symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates on radiologic exam, or oxygen saturation decline by ≥5 percent.
Intestinal perforation: Advise patients to promptly report any new or worsening abdominal pain, chills, fever, nausea, or vomiting.
Severe cutaneous reactions: One case of TEN occurred in a study of Zydelig in combination with rituximab and bendamustine. Other severe or life-threatening (grade ≥3) cutaneous reactions have been reported. Monitor patients for the development of severe cutaneous reactions and discontinue Zydelig if a reaction occurs.
Anaphylaxis: Serious allergic reactions including anaphylaxis have been reported. Discontinue Zydelig permanently and institute appropriate supportive measures if a reaction occurs.
Neutropenia: Treatment-emergent grade 3-4 neutropenia occurred in 31 percent of Zydelig-treated patients in clinical trials. In all patients, monitor blood counts ≥every 2 weeks for the first 3 months. In patients with neutrophil counts <1.0 Gi/L, monitor weekly.
Embryo-fetal toxicity: Zydelig may cause fetal harm. Women who are or become pregnant while taking Zydelig should be apprised of the potential hazard to the fetus. Advise women to avoid pregnancy while taking Zydelig and to use effective contraception during and at least 1 month after treatment with Zydelig.
Adverse Reactions
Most common adverse reactions (incidence ≥20 percent; all grades) in clinical studies, when used alone or in combination with rituximab, were diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills and rash.
Most frequent serious adverse reactions (SAR) in clinical studies in combination with rituximab were pneumonia (17 percent), pyrexia (9 percent), sepsis (8 percent), febrile neutropenia (5 percent), and diarrhea (5 percent); SAR were reported in 49 percent of patients and 10 percent of patients discontinued due to adverse reactions. Most frequent SAR in clinical studies when used alone were pneumonia (15 percent), diarrhea (11 percent) and pyrexia (9 percent); SAR were reported in 50 percent of patients and 53 percent of patients discontinued or interrupted therapy due to adverse reactions.
Most common lab abnormalities (incidence ≥30 percent; all grades) in clinical studies were neutropenia, hypertriglyceridemia, hyperglycemia and ALT/AST elevations.
Drug Interactions
CYP3A inducers: Avoid coadministration with strong CYP3A inducers.
CYP3A inhibitors: When coadministered with strong CYP3A inhibitors, monitor closely for Zydelig toxicity.
CYP3A substrates: Avoid coadministration with CYP3A substrates.
Dosage and Administration
Adult starting dose: One 150 mg tablet twice daily, swallowed whole with or without food. Continue treatment until disease progression or unacceptable toxicity. The safe dosing regimen for patients who require treatment longer than several months is unknown.
Dose modification: Consult the Zydelig full Prescribing Information for dose modification and monitoring recommendations for the following specific toxicities: pneumonitis, ALT/AST elevations, bilirubin elevations, diarrhea, neutropenia and thrombocytopenia. For other severe or life-threatening toxicities, withhold Zydelig until toxicity is resolved and reduce the dose to 100 mg, twice daily, upon resuming treatment. If severe or life-threatening toxicities recur upon rechallenge, Zydelig should be permanently discontinued.
about Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.
3、爱尔兰Shire公司巨资收购ArmaGen孤儿药AGT-182
爱尔兰特种药公司Shire公司7月23日 宣布，将斥资2.25亿美元从美国生物医学公司ArmaGen手中购买酵素替代疗法AGT-182，用于治疗亨特氏综合征所导致的中枢神经系统(CNS)和躯体症状。
根据双方协议，Shire 公司 将会先期支付ArmaGen1500万美元，并在之后的研发和销售达到预期目标之后向后者支付剩余部分。
双方约定，ArmaGen将会负责AGT-182临床I和II期研究，并计划在2014年年底之前正式启动。Shire Inc.将负责之后的临床研究以及产品营销。
美国食品药品监督管理局上周日授予AGT-182孤儿药认定。该项认定能减少企业税收、降低临床研究成本并在获批之后在美国享受7年产品专利保护期。
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4、BMS黑色素瘤药物Yervoy获英国NICE支持 发布日期：2014-07-24 来源：新药汇 浏览次数：6
百时美施贵宝抗癌药Yervoy获英国NICE支持，用于黑色素瘤的一线治疗。此外，百时美新一代黑色素瘤药物Opdivo近日获日本批准，该药为全球首个抗PD-1抑制剂。
英国国家健康与临床卓越研究所（NICE）发布指南，支持百时美施贵宝（BMS）抗癌药Yervoy（ipilimumab，易普利姆玛）用于英国国家卫生服务（NHS）。此前，Yervoy已推荐用于晚期恶性黑色素瘤的二线治疗，在新的指南中，NICE进一步支持Yervoy用于手术不可切除性或转移性黑色素瘤的一线治疗。这意味着，Yervoy可用于化疗前治疗。
Yervoy于2011年上市，该药在2013年的销售额近10亿美元。Yervoy获得额外适应症对于百时美施贵宝来说非常重要，因为目前黑色素瘤药物市场已出现数个极具竞争力的药物，包括葛兰素史克（GSK）的MEK抑制剂Mekinist（trametinib）和默沙东（Merck & Co）的免疫疗法pembrolizumab。
不过，百时美在研的新一代黑色素瘤药物nivolumab近日获得了利好消息，该药是一种抗PD-1抑制剂，于7月初获日本批准，是全球首个获批的抗PD-1药物，商品名为Opdivo（nivolumab）。百时美施贵宝近日表示，计划于2014年第三季度向FDA提交Opdivo的生物制品许可申请（BLA）。2013年，FDA已授予nivolumab治疗非小细胞肺癌（NSCLC）、黑色素瘤、肾细胞癌（RCC）的快车道地位。
关于Yervoy（ipilimumab）：
Yervoy是一种重组人单克隆抗体，阻断细胞毒性T淋巴细胞相关抗原4（CTLA-4）。CTLA-4是一种T细胞活化的负调控因子，Yervoy与CTLA-4结合后，能阻断CTLA-4与其配体CD80/CD86的相互作用。阻断CTLA-4已被证明能够增强T细胞的活化和增殖。Yervoy在黑色素瘤患者中的疗效作用机制，是间接通过T细胞介导的抗肿瘤免疫反应。FDA于2011年3月批准Yervoy 3mg/kg单药疗法用于不能手术切除或转移性黑色素瘤患者的治疗，目前该药已获全球40多个国家批准。
关于Opdivo（nivolumab，BMS-936559）:
癌细胞可能利用“调节子（regulator）”途径，如检查点（checkpoint）途径，逃避机体免疫系统，保护肿瘤免受免疫攻击。
nivolumab是一种实验性、全人源化IgG4、抗程序性死亡受体1（PD-1）单克隆抗体，能够抑制PD-1与程序性死亡配体1（PD-L1/B7-H1）和程序性死亡配体2（PD-L2/B7-DC）的结合。阻断PD-1与其配体的相互作用，可能使T细胞恢复抗肿瘤免疫应答。目前，百时美施贵宝正调查nivolumab用于恶性黑色素瘤、肾癌、非小细胞肺癌及其他癌症的治疗。
nivolumab的开发项目研究总数超过25个：调查作为单药疗法或与其他药物联合用药，用于多个肿瘤类型的治疗，包括：非小细胞肺癌、小细胞肺癌、黑色素瘤、肾细胞癌、肝癌、血液癌症、三阴性乳腺癌、胃癌、胰腺癌。
英文原文：NICE backs cancer drugs from Astellas and BMS
Recommendations for Xtandi in prostate cancer and earlier use of Yervoy
The National Institute for Health and Care Excellence (NICE) today backed two new cancer treatments for NHS use in England and Wales.
The guidance recommends a new skin cancer indication for Bristol-Myers Squibb's Yervoy (ipilimumab), while Astellas's Xtandi (enzalutamide) receives its first NICE recommendation for use in prostate cancer.
Yervoy is already recommended for NHS use as a second-line treatment for people with advanced malignant melanoma but this new guidance pushes the drug further up the treatment pathway as a first-line treatment if the tumour cannot be removed or the cancer has spread to other parts of the body.
This means the drug can be made available to cancer patients prior to chemotherapy.
As with the previous NICE guidance for Yervoy, the recommendation is dependent on BMS providing the drug at a discount through a patient access scheme.
Yervoy has performed well for BMS since launching in 2011, with sales of just under $1bn for 2013. Gaining extra indications is crucial for BMS, however, as more advanced rivals in melanoma hit or near the market, including GSK's MEK inhibitor Mekinist (trametinib) and Merck & Co's immunotherapy pembrolizumab.
BMS has its own next generation melanoma treatment in the works in the form of anti-PD1 inhibitor nivolumab. The drug was recently approved in Japan under the name Opdivo.
Xtandi recommended to treat prostate cancer
NICE's second recommendation was for the use of Astellas' Xtandi (enzalutamide) in the treatment of people with prostate cancer that has spread to other parts of the body.
These patients must also have been treated with the cytotoxic drug docetaxel and Astellas must provide Xtandi through a patient access scheme.
The decision follows a troubled path through NICE for Xtandi, which earlier this year was recommended in draft guidance that heavily restricted the use of the drug.
However, following consultation with Astellas and other parties, these restrictions were overturned.
Prof Carole Longson, director of the centre for health technology evaluation at NICE, said: ¡°Both cancer treatments are recommended on the basis that the manufacturers provide them to the NHS with a patient access scheme, wher there is a discount on the price of the drug.
¡°We are also very pleased that the manufacturers have worked with us to provide more evidence so that we are able to recommend both treatments.
5、安斯泰来抗癌药Xtandi获NICE支持
安斯泰来抗癌药Xtandi获英国NICE支持，用于英国国家卫生服务。该药是一种雄激素受体信号传导抑制剂，旨在干扰睾酮结合前列腺癌细胞的能力，于2012年获FDA批准。
英国国家健康与临床卓越研究所（NICE）发布指南，支持安斯泰来（Astellas）抗癌药Xtandi（enzalutamide）用于英国国家卫生服务（NHS），用于转移性前列腺癌的治疗。Xtandi在英国的上市之路可谓艰辛，今年早些时候，NICE曾发布指南草案，建议严格限制Xtandi的使用，后经安斯泰来与其他各方努力协商，这些限制最终被推翻。
NICE卫生技术评估中心主任Carole Longson教授表示，支持Xtandi用于NHS，是基于安斯泰来提供给NHS的患者获取方案，其中包括对Xtandi价格的折扣。
关于Xtandi（enzalutamide）：
Xtandi是一种新颖的、每日一次的口服雄激素受体信号传导抑制剂，该药能够抑制雄激素受体信号传导通路中的多个步骤，旨在干扰睾酮结合前列腺癌细胞的能力，已被证明能够降低癌细胞的生长，并能诱导肿瘤细胞死亡。睾酮是一种男性激素，能够激化前列腺癌细胞的生长。
Xtandi已于2012年8月获FDA批准用于经激素疗法及化疗后癌症已扩散的男性前列腺癌患者的治疗。
英文原文：NICE backs cancer drugs from Astellas and BMS
Recommendations for Xtandi in prostate cancer and earlier use of Yervoy
The National Institute for Health and Care Excellence (NICE) today backed two new cancer treatments for NHS use in England and Wales.
The guidance recommends a new skin cancer indication for Bristol-Myers Squibb's Yervoy (ipilimumab), while Astellas's Xtandi (enzalutamide) receives its first NICE recommendation for use in prostate cancer.
Yervoy is already recommended for NHS use as a second-line treatment for people with advanced malignant melanoma but this new guidance pushes the drug further up the treatment pathway as a first-line treatment if the tumour cannot be removed or the cancer has spread to other parts of the body.
This means the drug can be made available to cancer patients prior to chemotherapy.
As with the previous NICE guidance for Yervoy, the recommendation is dependent on BMS providing the drug at a discount through a patient access scheme.
Yervoy has performed well for BMS since launching in 2011, with sales of just under $1bn for 2013. Gaining extra indications is crucial for BMS, however, as more advanced rivals in melanoma hit or near the market, including GSK's MEK inhibitor Mekinist (trametinib) and Merck & Co's immunotherapy pembrolizumab.
BMS has its own next generation melanoma treatment in the works in the form of anti-PD1 inhibitor nivolumab. The drug was recently approved in Japan under the name Opdivo.
Xtandi recommended to treat prostate cancer
NICE's second recommendation was for the use of Astellas' Xtandi (enzalutamide) in the treatment of people with prostate cancer that has spread to other parts of the body.
These patients must also have been treated with the cytotoxic drug docetaxel and Astellas must provide Xtandi through a patient access scheme.
The decision follows a troubled path through NICE for Xtandi, which earlier this year was recommended in draft guidance that heavily restricted the use of the drug.
However, following consultation with Astellas and other parties, these restrictions were overturned.
Prof Carole Longson, director of the centre for health technology evaluation at NICE, said: ?°Both cancer treatments are recommended on the basis that the manufacturers provide them to the NHS with a patient access scheme, wher there is a discount on the price of the drug.
?°We are also very pleased that the manufacturers have worked with us to provide more evidence so that we are able to recommend both treatments.
6、吉利德血癌治疗新药Idelalisib获FDA批准
美国吉利德科学7月23日宣布，公司旗下血癌新药Idelalisib正式获得美国食品药品监督管理局（FDA）批准。该药物可用于复发慢性淋巴细胞白血病、滤泡淋巴瘤和小淋巴细胞性淋巴瘤的治疗。
7月23日，美国FDA批准了吉利德科学Idelalisib（商品名：Zydelig）的三个适应症：和利妥昔单抗（Rituxan）联合治疗复发的慢性淋巴细胞白血病（CLL）、作为单药治疗复发性滤泡B细胞非霍奇金淋巴瘤（FL）和复发性小淋巴细胞淋巴瘤（SLL）。FDA对后两个适应症是加速批准，且患者之前都至少接受过两次全身治疗。
FDA批准Idelalisib和利妥昔单抗复方治疗CLL是基于一个积极的国际、多中心、随机和安慰剂对照的三期临床实验（Study 116）结果。该临床实验招募了220位复发性的，但适用利妥昔单抗治疗的慢性淋巴细胞白血病（CLL）患者。其中一半患者每天口服两次，每次150毫克的idelalisib加利妥昔单抗（N=110），另一半采用利妥昔单抗和安慰剂（n=110）治疗。利妥昔单抗一共给药8次，第一次静脉注射375毫克/平米，随后每两周500毫克/平米输液3次和每4周500毫克/平米共输液4次。一级实验终点是无进展生存期（PFS），由一个独立的评审委员会（IRC）裁定。在平均给药5个月后，安慰剂/利妥昔单抗对照组无进展生存期的中位数为5.5个月，而idelalisib/利妥昔单抗治疗组因疗效明显而没有达到无进展生存期的中位数。因此，该临床实验被提前终止，对照组的患者被转换到治疗组。Idelalisib和利妥昔单抗联合用药组和对照组相比的总生存率（OS）和无进展生存期（PFS）分别延长了72%和82%。
Idelalisib单药的加速批准是基于一个单臂、多中心、开放标签的积极二期临床结果。该临床实验招募了123位复发性的“惰性”非霍奇金淋巴瘤（iNHL）和小淋巴细胞淋巴瘤（SLL）患者。病人每天接受两次，每次150毫克idelalisib治疗，一级实验终点是总应答率（ORR），二级实验终点是应答时间和无进展生存期。其中FL和SLL患者的总应答率分别为54%和58%。后者应答时间的中位数为11.9个月。这个结果和标准疗法的通常疗效相比相当或更好。
Idelalisib伴有一个黑框警告：提醒患者和保健人员idelalisib常常伴有肝脏毒性、严重腹泻或肠炎、以及肺炎和肠穿孔等副作用。其中发生率大于20%的不良反应有腹泻、发热、乏力、恶心、咳嗽、肺炎、腹痛、寒战和皮疹等。发生率大于30%的不良反应还有中性粒细胞减少、高甘油三酯血症、高血糖、ALT和AST值升高等。
Idelalisib是吉利德科学独具慧眼，继收购Sovaldi之后又一个成功的新药开发典范。尤其idelalisib的疗效是通过调节免疫系统，本身并不直接抑制肿瘤的生长，而且早期临床结果也并不令人过目难忘。正因为此，Idelalisib的早期开发充满了艰辛，Mike Gallatin经过了20次失败，才在第21次终于说服了Frazier Healthcare投资了这个被ICOS放在架子上数年的实验药。后来，Frazier Healthcare的2600万美元投资在短短3年之内增值到6亿美元
Idelalisib是首个上市的口服、选择性的磷酸肌醇3-激酶delta（PI3K-delta，P110-delta）抑制剂。P110-delta参与改变B淋巴细胞的免疫环境，对这类肿瘤细胞的活化、增殖、生存和迁移（trafficking）起着关键作用。Idelalisib的获批上市，为慢性淋巴细胞白血病（CLL）的治疗在ibrutinib之后又带来一个新的选择。在美国，慢性淋巴细胞白血病（CLL）在成人白血病患者中人数排第二，预计2014年会增添超过15000名新患者。包括Idelalisib和ibrutinib在内的CLL新药研发，有望把CLL从死刑判决演变成一种可控制的慢性疾病。当然，相应地CLL市场也逐渐扩大，彭博社分析师认为CLL市场不久将攀升到90亿美元。
7、重磅生物药专利悬崖推动生物仿制药黄金期 发布日期：2014-07-24 来源：新药汇 浏览次数：6
根据AlliedMarketingResearch(AMR)的最新研究，如果你将全球生物仿制药市场看成是一个整体，那么这是市场的总收入在2013年刚刚可以勉强达到一个重磅炸弹级药物的水平，为130亿美元。不过预计到2020年，随着新产品进入北美、欧洲和亚洲，这个市场的规模将增加到350亿美元。
推动这个市场的将是一些顶级生物药的专利悬崖。AMR发现，在未来四年内，有10个生物药将失去专利保护，它们销售额总计为600万美元。其中销售额最高的是修美乐（Humira），这个年销售额超过100亿美元的药物将在2016年失去专利保护。另外，赫思（Hospira）和Celltrion合作的类克（Remicade）的仿制药Inflectra已经获得了欧盟的批准，而强生公司即将于明年初在欧盟失去类克的专利保护，美国的专利也将在2018年到期。制药公司表示，他们计划打30%的折扣出售仿制药，这可能会成为生物仿制药的定价标准。AMR总结，欧洲是生物仿制药开发进展最大的地区，这一点也不令人惊讶。欧洲已经建立起一套关于生物仿制药开发的法规，并看成该行业全球的“风向标”。美国市场可能是全球最富有的，不过AMR的分析师指出，随着亚洲地区慢性病发病率的增长，对“价廉物美”的治疗药物的需求也不断增加，主要的制药公司联盟比如诺华（Novartis）和安进（Amgen）已经合作多年力图打开亚洲市场。亚洲、特别是印度，正已经逐渐成为生物仿制药先锋队中的领导者。知识产权保护一直是印度的一个大问题，但是宽松的监管也使产品更容易获得批准。而欧美国家、特别是美国正在努力地改善监管，这个更富有的市场将会迎头赶上。报告称，生物仿制药的开发商们正在把对知识产权保护不够的新兴市场作为跳板，以期进入成熟市场。随着成熟市场监管框架的日趋完善，生物仿制药的生产商将迅速进入这些市场。AMR强调，迈兰（Mylan）和Biocon合作在印度推出曲妥珠单抗的仿制药，以及Celltrion和赫思合作在欧洲上市英夫利西单抗，都是以上很好的例子。（生物谷Bioon.com）
8、军事医学科学院药物创新团队 发布日期：2014-07-24 来源：《中国科学报》 作者：王璐
军事医学科学院毒物药物研究所药物合成研究室不足百人，却拥有3个“国字号”名头。这个有着63年历史的功勋研究室，近日被解放军总后勤部授予“药物创新模范研究室”称号。
军事医学科学院毒物药物研究所药物创新团队成员实验室工作场景
研究室以刘克良、李松、仲伯华为首的药物创新团队，自主研制成抗流感病毒特效药“军科奥韦”等，使我国率先拥有全球品种最丰富的流感防控药物体系；主持建成全球单产能力最强的流感防控药物生产线，为我国13亿人口储备了世界最高质量标准的“救命药”；研制出为1亿多糖尿病患者减轻70%药费负担的Ⅱ型糖尿病药物“太罗”以及对抗“超级细菌”感染最后一道防线的“替加环素”。 临危受命，研制中国自己的“争气药” 2005年，H5N1禽流感显露出狰狞面目。我国政府迅速采取应对措施，同时向跨国制药公司定购50万人份达菲。这是当时世卫组织唯一指定的抗流感病毒特效药，但遭遇的却是漫长的等待期以及对方拒绝转让专利。 千钧一发之际，军事医学科学院科研人员挺身而出，决定自主研制抗流感病毒药物。很快，由药物合成研究室研制的“中国版达菲”—“军科奥韦”完成全部临床前工作，正式申报军队特需药品证书。同时，研发团队依靠拥有自主知识产权的生产工艺，将生产效率提高3倍，而且彻底避免了原工艺易发生爆炸、易产生致癌杂质的弊端。 “关键时刻一鸣惊人，靠的是前瞻部署的战略眼光和只争朝夕的拼搏精神。”中科院院士、军事医学科学院院长贺福初介绍说，“早在2003年，团队就开始了相关研究工作。那时，我们意识到SARS疫情之所以难以遏制，缺乏有效的防治药物是重要原因，而流感是下一轮最有可能突然来袭的重大疫情。医学科研工作者有责任为此作好充分准备。” 终于，李松团队成功研制出“军科奥韦”，并获得我军规范药品审批制度以来第一份新药证书—“军药001”号。 此外，为解决儿童、老人、重症患者服药难题，他们研发了全球唯一的“磷酸奥司他韦颗粒剂”；为应对“磷酸奥司他韦”大量使用可能产生的耐药性，研发出抗病毒活性更强的“帕拉米韦”。 2009年，北美暴发H1N1流感疫情。该团队再次立下军令状，最终1300万人份的生产任务提前18天完成。当年，共生产储备2.6亿剂“磷酸奥司他韦”。这批药即便能从罗氏公司买到，也要多花58亿元。 打破垄断，研制老百姓用得起的“民生药” 2013年3月29日，在抗多重耐药细菌感染新药“替加环素”上市发布会上，发明人李松在签署成果转让协议后说：“替加环素是目前为止对抗超级细菌的最后一道防线。虽然已成功上市，我却希望生产企业不要为了经济利益大量销售。无论什么时候，国家安全、百姓健康才是我们的最终目的。” 军事医学科学院政委高福锁告诉记者：“当时我在现场，听完非常感动。这就是有责任、有担当的科学家的胸怀。” 上世纪50年代，研究员张其楷率领科研团队打破国外经济封锁，完成了当时急需的抗丝虫病新药“益群生”和抗结核病新药“异烟肼”的合成研究工作，最终推动药物投产和临床应用。 上世纪90年代，糖尿病在我国的发病率快速上升，并缺少有效治疗药物。研究室首先瞄准了这一关系民生的战略性药品。 化合物罗格列酮是当时的热门研发产品。美国葛兰素史克公司率先研发出“马来酸罗格列酮”并上市，商品名为“文迪雅”，并将所有酸式盐组合物申请了专利。当时科学界普遍认为，“罗格列酮”不能生成碱式盐。 不过，李松坚信，科学上不存在绝对。通过大量理论分析和量化计算后，他们终于发现罗格列酮一个键上的氢呈现酸性，应用强碱可以生成碱式盐。这让该团队顺利合成全球唯一的罗格列酮钠盐制剂。2004年，在此基础上研发的治疗Ⅱ型糖尿病药物“太罗”上市。 “太罗”的上市，迫使“文迪雅”从每粒不低于20元降到每粒13元。而每剂4元、疗效显著的“太罗”成为名副其实的“平价药”“民生药”。 2011年1月14日，国家科学技术奖励大会上，“太罗”继获得中国发明专利金奖之后，再次获得国家技术发明奖二等奖。 永不言败，研制自主品牌“原创药” 长期以来，民族制药企业一直对完全自主创新药物的研发望而却步。面对这块难啃的“硬骨头”，研究室药物创新团队决心从源头上创新，加速新药的中国原创。 他们以仿制药物研发和产业化反哺创新药物研究，逐渐建立起世界一流的科研平台。自主创新的基因，早就融于团队研发人员的血液。 上世纪50年代研究室成立之初，科研人员针对乙酰胆碱酯酶的重活化和保护，先后收集了15000多个化合物，并通过结构优化设计合成了数以万计的新结构化合物，最终筛选出一批特效抗毒化合物组成复方。这一系列我军独创的特效解毒药，有数个目前仍为代表新药创制最高水平的新化学实体。 而每研制一个新药，科研人员都要像神农尝百草一样亲自参加人体试验。据统计，先后参加试服试注试用的科研人员累计3000多人次，最高服用剂量为临床应用的8倍。他们常说，为了战士们的健康，这点皮肉苦也是一种幸福。 凭借着这种奉献精神，该研究室圆满完成全部应急科研、药品储备和反恐备勤任务。 近年来，该研究室先后申请发明专利153件，获中、美、欧盟等国家和地区授权发明专利110件，获中国发明专利金奖1项，获国家新药证书27项，获国家科技进步奖一等奖、国家技术发明奖二等奖等高等级奖励10项。 “这个不足百人的研究室，始终坚持把为战斗力服务、为官兵健康服务作为尽责之本，将药物研发与人民群众的健康紧密相联。”高福锁表示，他们将继续通过军民融合式发展道路，把科学技术不断转化为战斗力、生产力。 9、AbbVie顺手牵羊拿到Gilead的组合抗丙肝疗法专利
一般如果自己没有化合物专利，是不会去研究组合物的，因为即便研究成功了，自己也不能上市销售。但AbbVie这个案例就是个奇葩，它自己一开始就打算开发组合抗丙肝疗法，还顺手牵羊覆盖了ledipasvir+sofosbuvir。
Gilead去年年底上市Sovaldi，作为非罕见病药物定价高达1000美元/片，上市后第一季度为22.7亿美元，创下医药史上的奇迹。然而Sovaldi只对GT2、GT3两个亚型纯口服，对于GT1、GT4亚型仍然需要与干扰素联用，组合抗丙肝疗法不仅疗效比Sovaldi更好，对GT1型也是纯口服，成为各大公司争夺的焦点。FDA目前认定了四种突破性的组合抗丙肝疗法，分别是Gilead的sofosbuvir+ledipasvir二联、Merck的MK-5172+MK-8742二联，AbbVie的ABT-450/r+ABT-267+ABT-333三联、Bristol-Myers Squibb的daclatasvir+asunaprevir+BMS-791325三联。这些药物对GT1型丙肝的治愈率在95%以上，某些试验中甚至高达100%。2月10日Gilead率先递交ledipasvir+sofosbuvir二联上市申请，4月7日获得FDA优先审评资格，PDUFA日期提前到2014年10月10日，Gilead极有可能再下一城，成为首个上市组合抗丙肝疗法的厂家，在丙肝治疗领域拿到绝对的统治权。去年Gilead面对Merck、Roche、Idenix轮番敲诈寸步不让，这次却迎来了新的对手，AbbVie宣称他们2011年10月21日申请了两项专利，覆盖了ledipasvir+sofosbuvir这个组合，如果Gilead上市销售sofosbuvir+ledipasvir二联则侵权。AbbVie组合物专利：US8466159、US8492386
Gilead回击称他们拥有sofosbuvir、ledipasvir单独的化合物专利[3]，而且在2011年9月16日递交了分案申请，公开了sofosbuvir+ledipasvir这个组合，比AbbVie的组合物专利申请早了一个月。两家公司争论的焦点是，AbbVie组合物专利的组合物专利是否有效。ledipasvir化合物专利：US8088368、US8273341、US8575118sofosbuvir化合物专利：US7964580、US8334270、US8580765AbbVie是把各公司的抗丙肝化合物全部拿过来（总共70个），然后搭配出不同的组合，要求保护在他们之前尚未公开的许多个组合，其中就包括ledipasvir+sofosbuvir。一般如果自己没有化合物专利，是不会去研究组合物的，因为即便研究成功了，自己也不能上市销售。但AbbVie这个案例就是个奇葩，它自己一开始就打算开发组合抗丙肝疗法，还顺手牵羊覆盖了ledipasvir+sofosbuvir。Gilead的主要观点是他们在2012年4月才公布ledipasvir所对应的化学结构，在此之前它只是一个代号，AbbVie不可能知道这个化合物的结构，也不可能拿去做组合疗法。而且AbbVie在专利中没有给出ledipasvir的化学结构，没有说明如何制造ledipasvir，没有ledipasvir+sofosbuvir的具体实施例和数据。现在这个案子变得扑朔迷离了，AbbVie不一定要完全赢得官司，给Gilead使点绊子，让它不那么顺利就达到目的了。AbbVie是4月22日递交ABT-450+ABT-267+ABT-333三联上市申请，并于6月13日拿到FDA优先审评资格，比Gilead仅仅晚了两个月。
10、UCB公布癫痫药物brivaracetam（布瓦西坦）III期研究积极顶线数据
比利时制药巨头优时比（UCB）7月23日公布了癫痫药物brivaracetam（布瓦西坦）一项为期12周的III期研究的积极顶线数据。
比利时制药巨头优时比（UCB）7月23日公布了癫痫药物brivaracetam（布瓦西坦）一项为期12周的III期研究的积极顶线数据。该项研究在768例伴有部分性发作（POS）但经1种或2种抗癫痫药物（AED）联合用药不能完全控制病情的局灶性癫痫（focal epilepsy）成人患者中开展，调查了brivaracetam（100和200mg/天）相对于安慰剂的疗效和安全性，研究中，将brivaracetam作为一种辅助药物用于患者的治疗。数据表明，与安慰剂相比，brivaracetam可显著降低部分性发作频率并改善反应率，2者均具有统计学显著差异。研究中brivaracetam耐受性与既往研究一致，最常见的不良反应包括嗜睡、头晕、乏力和头痛。该项研究的详细数据，将提交至未来的科学会议。根据该研究的数据，UCB计划于2015年分别向FDA和欧洲药品管理局（EMA）提交brivaracetam的新药申请（NDA）和上市许可申请（MAA）。如果获批，brivaracetam将成为UCB旗帜性癫痫专营权中的第3个上市产品。UCB公司最畅销的药物为Keppra，该药专利于2011年到期，在2013年的销售额已下跌15%至9.59亿美元。UCB的另一个产品Vimpat于2008年获批作为辅助药物，该药的销售在2013年增长23%至5.53亿美元，该公司正在开展后期研究，寻求批准该药用于儿科患者，同时作为成人患者的单药疗法。UCB公司2015年即将上任的新首席，正密谋摆脱对中枢神经系统专营权的的依赖，寻求在免疫学领域建立一个新的生物制剂专营权，在该领域中，单抗药物Cimzia（certolizumab，赛妥珠单抗）已获批用于类风湿性关节炎、克罗恩病、银屑病关节炎的治疗，除此之外，UCB也正在开发狼疮、骨质疏松症及其他免疫疾病的药物。brivaracetam为西坦类衍生物，具有广泛的抗癫痫活性和较高的安全性，该药可通过与突触囊泡蛋白2A(SV2A)结合而发挥抗癫痫作用。英文原文：Major advance in UCB pipeline: positive topline Phase 3 results for brivaracetam in epilepsy patients with partial-onset seizures•Brivaracetam is the newest investigational medicine to emerge from UCB’s rich late-stage pipeline• Submissions to US and EU regulatory authorities planned for early 2015: subject to approval as adjunctive treatment for partial-onset seizures in adult epilepsy patients, brivaracetam would provide a new option for people with uncontrolled seizures• Brivaracetam clinical development program has involved over 3,000 people and offers over 8 years of clinical experience with some patients1Brussels (Belgium), 23rd July 2014 – 0700 (CEST) – regulated information – UCB today announced an important advance in its research and development pipeline with positive topline results from the latest Phase 3 study with brivaracetam. This study was designed to evaluate the efficacy and safety of brivaracetam (100 and 200 mg/day, without titration) compared to placebo, as adjunctive treatment in adult focal epilepsy patients with partial-onset seizures, not fully controlled despite treatment with one or two concomitant antiepileptic drugs (AEDs).2Results showed that brivaracetam reduced partial-onset seizure frequency and improved responder rates, both with statistical significance. The most commonly reported adverse events were somnolence, dizziness, fatigue and headache.3“Today’s positive results with brivaracetam represent a significant milestone in our strategy to deliver new treatment options for people with severe diseases. As the newest product to emerge from our late-stage pipeline, brivaracetam is leading the way for UCB’s new era of patient-centric solutions,” said Jean-Christophe Tellier, CEO-Elect, UCB. “We are proud to provide AED options for the epilepsy community today, and remain committed to addressing the unmet needs of adult patients who continue to experience uncontrolled seizures.”“The positive data from the most recent Phase 3 study demonstrated robust and clinically relevant seizure reduction in predominantly treatment resistant patients, and tolerability was consistent with previous brivaracetam trials4-6,” said Professor Dr. Iris Loew Friedrich, Chief Medical Officer and Executive Vice President, UCB. “This study was the largest Phase 3 study conducted in epilepsy patients with partial-onset seizures. Overall, the brivaracetam development program has involved over 3,000 people and offers over eight years of clinical experience with some patients.1 We look forward to discussing the data with the regulatory authorities and the scientific community.”based on the results of the brivaracetam Phase 3 program, UCB plans to submit a New Drug Application to the US Food & Drug Administration (FDA) and a Marketing Authorization Application to the European Medicines Agency (EMA) in early 2015.This Phase 3 study was a randomized, double-blind, placebo-controlled, multicentre, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam (100 and 200 mg/day) compared to placebo, over a 12-week treatment period, in 768 randomized focal epilepsy patients (aged 16 to 80 years) with partial-onset seizures, not fully controlled despite treatment with one or two concomitant AEDs.2,7 The primary endpoint for the European regulatory authorities is the 50% responder rate for partial-onset seizure frequency compared with placebo, over the treatment period standardized to a 28-day duration. The primary endpoint for the FDA is the percent reduction over placebo for partial-onset seizure frequency, over the treatment period standardized to a 28-day duration.2 Detailed data from this study will be submitted for presentation at upcoming epilepsy congresses and for publications in peer-reviewed journals.about brivaracetam and the Phase 3 clinical development program
Discovered and developed by UCB, brivaracetam is a highly selective synaptic vesicle protein 2A ligand.8,9The phase 3 clinical development plan for brivaracetam consisted of the following studies:N01252: an evaluation of the efficacy and safety/tolerability of adjunctive brivaracetam 20, 50, and 100 mg/day compared with placebo over 12 weeks, in 399 randomized patients (16 to 70 years) with partial-onset seizures not fully controlled despite treatment with 1-2 concomitant AEDs.4N01253: an evaluation of the efficacy and safety/tolerability of adjunctive brivaracetam at doses of 5, 20, and 50 mg/day compared with placebo over 12 weeks, in 400 randomized patients (16 to 70 years) with partial-onset seizures, not fully controlled despite treatment with 1-2 concomitant AEDs.5N01254: an evaluation of the safety and tolerability of adjunctive brivaracetam given at individualized tailored doses between 20 and 150 mg/day, compared with placebo over 16 weeks, in 480 randomized patients (≥16 to 70 years) with uncontrolled epilepsy (up to 20% could be patients with generalized epilepsy), not fully controlled despite treatment with 1-3 concomitant AEDs.6N01358: an evaluation of the efficacy and safety of adjunctive brivaracetam 100 and 200 mg/day compared with placebo over 12 weeks in 768 randomized patients (≥16 to 80 years) with partial-onset seizures, not fully controlled despite treatment with 1-2 concomitant AEDs.2,7about Epilepsy10,11,12Epilepsy is a chronic neurological disorder affecting approximately 65 million people worldwide. It is considered to be a disease of the brain defined by any of the following conditions: (1) at least two unprovoked (or reflex) seizures occurring >24 hours apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome.Although epilepsy may be linked to factors such as health conditions, race and age, it can develop in anyone at any age, and approximately 1 in 26 people will develop epilepsy in their lifetime.Partial seizures begin with an electrical discharge in one area of the brain. Different things can cause partial seizures, for example head injury, brain infection, stroke, tumour, and changes in the way an area of the brain was formed before birth, called cortical dysplasias. Many times, no known cause is found, but genetic factors may be important in some partial seizuresabout UCB in EpilepsyUCB has a rich heritage in epilepsy with over 20 years of experience in the research and development of antiepileptic drugs. As a company with a long-term commitment to epilepsy research our goal is to address unmet medical needs. Our scientists are proud to contribute to advances in the understanding of epilepsy and its treatment. We partner and create super-networks with world-leading scientists and clinicians in academic institutions, pharmaceutical companies and other organizations who share our goals. At UCB, we are inspired by patients and driven by science in our commitment to support patients with epilepsy.
11、Puma公布实验性抗癌药neratinib（来那替尼）III期临床研究积极数据
Puma抗癌药neratinib III期临床大获成功，股价暴涨220%。此前，该药在II期临床中击败罗氏重磅药物赫赛汀（Herceptin），有分析师预测，该药上市后的峰值将超过60亿美元。
生物技术公司Puma 7月23日公布了实验性抗癌药neratinib（来那替尼，代码PB272）III期临床研究（ExteNET）的积极顶线数据。ExteNET研究是一项双盲、安慰剂对照III期研究，在2812例已接受手术和赫赛汀（Herceptin）辅助治疗的早期HER2阳性乳腺癌女性患者中开展，研究中，患者在完成赫赛汀辅助治疗后，随机分配接受为期一年的neratinib或安慰剂辅助治疗。试验中，患者随机化分配之后开始进行2年时间的随访，统计疾病复发、原位性管腺癌（DCIS）或死亡，该研究的主要终点为无病生存期（DFS）。数据表明，与安慰剂相比，neratinib使无病生存期改善33%，具有统计学显著差异（p=0.0046）。此外，与安慰剂相比，neratinib使次要终点原位性管腺癌无病生存期（DFS-DCIS）改善达37%，同样具有统计学显著差异（p=0.0009）。该项研究的详细数据将提交至未来的科学会议。根据该项研究的积极数据，Puma计划于2015年第一季度向FDA提交neratinib的监管文件，寻求批准用于扩展期辅助治疗。消息发布后，Puma公司股价暴涨220%。关于neratinib在III期临床的出彩表现，分析师们持有不同的乐观意见。一些分析师认为，该药的III期成功，有望使neratinib成为年销售额突破10亿美元的重磅药物。而另一些分析师认为，该药将在2028年达到60亿美元的销售峰值。今年4月，Puma公布了neratinib一项II期研究（I-SPY 2）的积极数据，表明neratinib用于HER2阳性乳腺癌时，疗效优于罗氏赫赛汀。关于neratinib：
neratinib是一种口服、不可逆、泛ErbB受体酪氨酸激酶抑制剂，能有效抑制ErbB1和ErbB2，其作用机制与罗氏赫赛汀（曲妥珠单抗）及乳腺癌新药Perjeta（帕妥珠单抗）不同，后2者为单克隆抗体药物，靶向于HER2阳性癌细胞表面的HER2受体。Perjeta联合Herceptin及多西紫杉醇化疗被认为能够对HER2信号传导通路提供更全面的封锁。英文原文：Puma Biotechnology Announces Positive Top Line Results from Phase III PB272 Trial in Adjuvant Breast Cancer (ExteNET Trial)Neratinib Achieves Statistically Significant Improvement in Disease Free Survival Company Plans to File for Regulatory Approval in First Half of 2015LOS ANGELES, Calif., July 22, 2014 - Puma Biotechnology, Inc. (NYSE: PBYI), a development stage biopharmaceutical company, announced top line results from the Phase III clinical trial of Puma's investigational drug PB272 (neratinib) for the extended adjuvant treatment of breast cancer (ExteNET Trial). The ExteNET trial is a double-blind, placebo-controlled, Phase III trial of neratinib versus placebo after adjuvant treatment with trastuzumab (Herceptin) in women with early stage HER2-positive breast cancer.More specifically, the ExteNET trial enrolled 2,821 patients in 41 countries with early-stage HER2-positive breast cancer who had undergone surgery and adjuvant treatment with trastuzumab. After completion of adjuvant treatment with trastuzumab, patients were randomized to receive extended adjuvant treatment with either neratinib or placebo for a period of one year. Patients were then followed for recurrent disease, ductal carcinoma in situ (DCIS), or death for a period of two years after randomization in the trial.The primary endpoint of the trial was disease free survival (DFS). The results of the trial demonstrated that treatment with neratinib resulted in a 33% improvement in disease free survival versus placebo. The hazard ratio was determined to be 0.67 which was statistically significant with a p-value of 0.0046. The secondary endpoint of the trial was disease free survival including ductal carcinoma in situ (DFS-DCIS). The results of the trial demonstrated that treatment with neratinib resulted in a 37% improvement in disease free survival including ductal carcinoma in situ versus placebo. The hazard ratio was determined to be 0.63 which was statistically significant with a p-value of 0.0009. based on these results from the ExteNET study, Puma plans to file for regulatory approval of neratinib in the extended adjuvant setting in the first half of 2015.Full results of the ExteNET trial for PB272 will be presented at a future scientific meeting“We are very pleased with the results of the ExteNET trial with neratinib. This represents the first trial with a HER2 targeted agent that has shown a statistically significant benefit in the extended adjuvant setting, which we believe provides a meaningful point of differentiation for neratinib in the treatment of HER2 positive breast cancer,” said Alan H. Auerbach, Chief Executive Officer and President. “While the use of trastuzumab in the adjuvant setting has led to a reduction in disease recurrence in patients with early stage HER2-positive breast cancer, there remains an unmet clinical need for further improvement in outcome in order to attempt to further reduce this risk of recurrence. The results of the ExteNET study demonstrate that we may be able to provide this type of improvement with neratinib to further help the patients with this disease.”Puma Biotechnology Announces Amendment to Neratinib Licensing Agreement with PfizerLOS ANGELES, Calif., July 22, 2014 - Puma Biotechnology, Inc. (NYSE: PBYI), a development stage biopharmaceutical company, announced an amendment to its licensing agreement with Pfizer for Puma's investigational drug PB272 (neratinib). Puma is currently developing PB272 for the treatment of patients with HER2-positive breast cancer and patients with non-small cell lung cancer, breast cancer and other solid tumors that have a HER2 mutation.At the time that Puma licensed PB272 from Pfizer, a number of ongoing clinical trials (legacy clinical trials) that had been previously initiated by Pfizer were transferred to Puma. The original license agreement set a limit on the amount of external expenses that Puma would incur in completing these legacy clinical trials. Puma reached this limit in the fourth quarter of 2012. The original license agreement also provided that Pfizer would be responsible for all expenses for these ongoing legacy trials above the pre-determined limit until the trials were completed.The amendment to the license agreement provides that Puma will now be solely responsible for the expenses associated with the ongoing legacy clinical trials. Puma anticipates that this will result in an increase in research and development expenses, which will total approximately $30 million. Puma further anticipates that a significant percentage of this approximately $30 million will occur in 2014 and will decrease over time until the trials are completed.In addition, according to the terms of the original license agreement, upon commercialization of neratinib, Puma is obligated to pay Pfizer incremental annual royalties ranging between 10 to 20 percent of net sales of neratinib. Under the terms of the amendment to the license agreement, upon commercialization of neratinib, Puma will be obligated to pay Pfizer annual royalties on net sales of neratinib at a fixed rate in the low- to mid- teens.“We are pleased to enter into this amendment to the licensing agreement for neratinib. By assuming responsibility for the expenses associated with the ongoing legacy clinical trials, and by fixing the royalty rate for the drug at a reduced rate, we believe that we have significantly improved the potential value of the drug,” said Alan H. Auerbach, Chief Executive Officer and President.
12、FDA批准Avanir公司重度抑郁症药物AVP-786开展II期临床
近日，美国食品药品监督管理局（FDA）批准了Avanir制药公司有关评价其新一代重度抑郁症药物——AVP-786安全性和有效性的II期临床研究申请。
近日，美国食品药品监督管理局（FDA）批准了Avanir制药公司有关评价其新一代重度抑郁症(major depressive disorder，MDD)药物——AVP-786安全性和有效性的II期临床研究申请(investigational new drug，IND)。Avanir计划于2014年3季度开展评价AVP-786作为MDD辅助治疗方案的这项II期临床试验。Avanir制药CEO，Joao Siffert说：“此项临床试验获得了FDA精神障碍疾病药物分部的支持，可加快AVP-786的发展，同时也可以参考AVP-923发展计划过程中产生的大量数据。对于公司来说，临床试验申请获批是非常重要的一刻，这也是AVP-786第一个招募相应患者参与的临床试验。目前有数以百万计的MDD患者对现有疗法反应不佳。由于AVP-786的机制能够对多种与抑郁症相关的神经递质系统起作用，如能获批，AVP-786将可能为MDD患者提供一种潜在的新治疗选择。我们非常期待在接下来的几个月里启动该临床研究计划。”此次IND的提交代表了Avanir制药公司计划对AVP-786在神经和精神系统疾病方面发展的第一步。该II期临床试验将要评价AVP-786用于对常用抗抑郁处方药（包括选择性5-羟色胺再摄取抑制剂SSRIs和5-羟色胺去甲肾上腺素再摄取抑制剂SNRIs）反应不佳的MDD患者的安全性和有效性，属于多中心、随机、双盲、安慰剂对照的概念验证性试验，将在美国招募200名受试者。在为期10周的试验时间内，符合条件的受试者将随机分配到AVP-786组和安慰剂组。
13、Janssen将开展daratumumab治疗多发性骨髓瘤新III期临床试验
于2014年4季度开始daratumumab用于多发性骨髓瘤患者的新III期临床试验。
Genmab公司的合作伙伴——Janssen Biotech(Janssen)公司宣布计划将于2014年4季度开始daratumumab用于多发性骨髓瘤患者的新III期临床试验。该III期临床试验旨在比较daratumumab联合硼替佐米、美法仑、泼尼松和仅使用硼替佐米、美法仑、泼尼松，用于不适合干细胞移植(stem cell transplantation，SCT)的多发性骨髓瘤患者的一线治疗的效果和安全性。Genmab公司CEO Jan van deWinkel称，公司非常高兴地宣布将进行daratumumab的第三个III期临床试验，我们与Janssen公司共同制定的稳健发展计划正快速前进。该III期临床试验计划招募700名新诊断的、不适合SCT并未接受过化疗的多发性骨髓瘤患者。试验中患者将随机分组，分别接受daratumumab、硼替佐米、美法仑以及泼尼松的药物组合以及硼替佐米、美法仑、泼尼松药物组合。这项随机、开放、多中心的III期临床试验的首要终点是无进展生存期（PFS）。硼替佐米作为蛋白酶体抑制剂，是一种较为特殊的化疗药物，而美法仑则是一种烷化剂类化疗药物。
14、Cerecor筹集资金用于“SpecialK”抑郁症药物CERC-301进入2期研究 发布日期：2014-07-24 来源：fiercebiotech
位于巴尔的摩的Cerecor公司已经筹集了B轮投资3300万美元的一半，并计划为一项中期研究项目投入大量资金，该项目是默克重组期间放弃的抑郁症实验药物。
位于巴尔的摩的Cerecor公司已经筹集了B轮投资3300万美元的一半，并计划为一项中期研究项目投入大量资金，该项目是默克重组期间放弃的抑郁症实验药物。在提交给SEC的文件中，该公司指出它已筹集了3320万美元计划中的第一轮1620万美元资金。新企业协会，苹果树合作伙伴和MPM资本主导了首轮投资，这也将资助其研发的儿茶酚-O-甲基转移酶抑制剂平台，该平台以“执行功能和工作记忆的障碍为特征。”Cerecor的主要项目是CERC-301，目的是为了检验一个理论，即阻断NMDA受体途径可以迅速而显着地改善重度抑郁症的症状，甚至对多年难治性的患者也有效。目前很多相关工作一直围绕着类似药物氯胺酮，或Special K来开展，，众所周知这些物质在短期内对NMDA有很大的影响。一系列短期和早期阶段的临床试验中使用这些药物加强了其见效快的证据。氯胺酮的优点是它似乎能修复脑部被损坏的复杂神经信号系统。但包括阿斯利康在内的开发商都遇到了一系列的挫折。强生公司推动了药物esketamine的鼻腔制剂进入2期试验，并戏称其为公司最具实验性的疗法之一。阿斯利康有一个氯胺酮类药物AZD6765已经进入2期阶段，但其错过了两个中期试验终点后，这个项目又很快被悄悄停止。当时阿斯利康没有提供项目发生什么错误的数据或详细的解释。这次挫折也没有吸引与成功相关的重大新闻报道。Cerecor是由Paterson主导开发，他是阿尔巴医疗公司的创始人和前CEO。目前主席为Celgene公司前首席执行官Bare，他最近把4家生物技术公司合并成一个单一的药物开发机构，即RestorGenex，专注于皮肤科、眼科疾病和妇女健康。Paterson在声明中称，“这次融资使Cerecor能够继续推进神经系统疾病的化合物，包括CERC-301进入2期发展，它有可能挽救严重抑郁症患者的生命，阻止其自杀意念的形成。我们正在积累氯胺酮静脉注射剂方面和更多的选择性和特异性的口服剂方面丰富的临床经验，使其具有可提高安全性的潜力。”信源地址：http://www.fiercebiotech.com/sto ... n-remedy/2014-07-21
15、对乙酰氨基酚治疗腰痛无明显效果 发布日期：2014-07-24 来源：The Lancet
据近期1项大规模随机试验结果表明，与安慰剂相比，对乙酰氨基酚在缓解腰痛急性发作和改善疼痛水平、功能、睡眠及生活质量上并无明显优势。
据近期1项大规模随机试验结果表明，与安慰剂相比，对乙酰氨基酚在缓解腰痛急性发作和改善疼痛水平、功能、睡眠及生活质量上并无明显优势。对乙酰氨基酚作为治疗腰痛的首选镇痛药已经众人皆知，但该项试验对此提出了质疑。文章发表在2014年7月24日The Lancet杂志上。腰痛已经是世界范围内致残的重要原因。大多数临床指南普遍建议对乙酰氨基酚为治疗急性腰痛的首选镇痛药，然而并没有相关的基础研究证实对乙酰氨基酚治疗腰痛有效。对乙酰氨基酚治疗腰痛研究小组（PACE）随机从悉尼235家初级护理中心纳入1652例腰痛患者。平均年龄45岁，随机把相同数量的患者分为常规剂量组（连续定期服用4周对乙酰氨基酚，每日3次，相当于每日3990 mg）、按需服用组（按患者需求服用，最大每日剂量不超过4000 mg）和对照组（服用安慰剂）。服药结束后，三组均接受持续3个月的随访。试验结果显示三组在恢复时间上无明显差别，中位恢复时间分别为17天（常规剂量组），17天（按需服用组）和16天（对照组）。在缓解短期疼痛、伤残、功能、睡眠及生活质量水平上，对乙酰氨基酚的效果也不明显。而且，各组发生副作用的人数基本相等。“像对乙酰氨基酚这样的一般镇痛药，在治疗急性腰痛患者中不应该扮演如此重要的角色。”文章第一作者，来自澳大利亚悉尼大学乔治全球健康研究院Christopher Williams博士说道，“研究结果提示，虽然对乙酰氨基酚能有效缓解其他类型疼痛，但我们应该重新评估对乙酰氨基酚作为腰痛治疗一线药物的观点，这直接关系到患者后续治疗的计划。Williams博士还补充道：“鉴于本次试验周期较短，我们非常想知道，究竟是心理安慰还是药理作用在治疗腰痛急性发作上更为有效。”来自荷兰鹿特丹Erasmus大学医学中心Bart Koes和Wendy Enthoven教授评论认为，“Williams博士和他的团队能够质疑我们长久以来约定俗成的观点，这是非常值得鼓励的事情。尽管本次高质量试验研究结论非常明确，但指南的修改不能基于这一次试验，而还需要更多的试验结果辅佐。此外，今后的研究可致力于其他一般的镇痛药是否会给腰痛患者带来额外的心理安慰作用。”信源地址：http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60805-9/fulltext
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