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标题: 2014-9-19国内、国际新药信息大汇总（一） [打印本页]

作者: 静悄悄 时间: 2014-9-19 02:00 PM
标题: 2014-9-19国内、国际新药信息大汇总（一）
2014-9-19国内、国际新药信息大汇总（一）

1、诺华骨髓瘤新药LBH589联用大幅提高无进展生存期

发布日期：2014-09-19 来源：nasdaq

诺华9月19日宣布，公司在研新药LBH589联合硼替佐米和地塞米松在4个月的临床III期试验中能大幅度提高复发性、多发性骨髓瘤患者的无进展生存期。该研究刊登于《柳叶刀肿瘤学》杂志。

　　与此同时，数据显示，联合用药增加患者总体应答率和应答时间。LBH589是一种泛脱乙酰酶抑制剂，该药物于今年5月被美国食品药品监督管理局（FDA）授予优先审批通道。

　　公司此次进行的是随机、双盲、安慰剂对照的临床III期研究，共有来自全球215个中心的768位患者参与。

Novartis data in The Lancet oncology show LBH589 offers 4-month increase in median PFS for patients with multiple myeloma

Novartis International AG / Novartis data in The Lancet oncology show LBH589 offers 4-month increase in median PFS for patients with multiple myeloma . Processed and transmitted by NASDAQ OMX Corporate Solutions. The issuer is solely responsible for the content of this announcement.

· Results show statistically significant and clinically relevant increase in median progression-free survival with LBH589 plus bortezomib and dexamethasone[1]

· LBH589, a first-in-class treatment for patients with relapsed/refractory multiple myeloma if approved, helps extend benefit of standard-of-care therapy[1]

· First Phase III study to demonstrate superiority of a three-drug over two-drug combination in this patient population[1]

· Multiple myeloma, the second most common blood cancer, is incurable; most patients will relapse or become refractory so new treatments are needed[2],[3]

basel, September 19, 2014- Data published today in The Lancet oncology demonstrated a statistically significant and clinically relevant 4-month improvement in median progression-free survival (PFS) (hazard ratio=0.63 [95% confidence interval (CI): 0.52 to 0.76]; p<0.0001) for patients with relapsed or relapsed and refractory multiple myeloma when using the investigational compound LBH589 (panobinostat) in combination with bortezomib* and dexamethasone compared to placebo plus the same combination[1]. In the Phase III PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) trial, the addition of LBH589 also led to clinically meaningful increases in complete and near complete response rates and duration of response. The effect of LBH589 was observed across all patient subgroups[1].

Multiple myeloma is a cancer of white blood cells that predominantly affects the bone marrow, impacting approximately 1 to 5 in every 100,000 people worldwide each year, and is increasing in prevelance[4],[5]. Most people with multiple myeloma ultimately relapse and become resistant to treatment, so new therapies with novel mechanisms of action are critical for continuing to manage the disease and improve outcomes[3]. If approved, LBH589, a pan-deacetylase (pan-DAC) inhibitor, will be first in its class of anticancer agents available to this population[1].

"The PANORAMA-1 study is the first Phase III trial to show the superiority of LBH589 plus bortezomib and dexamethasone over one of the standard two-drug regimens for patients with relapsing and/or refractory multiple myeloma," said lead study investigator Jesus San-Miguel, MD, Director of Clinical and Translational Medicine, Clínica Universidad de Navarra, Pamplona, Spain. "These results show that by adding a new mechanism of action, pan-DAC inhibition, there is a significant benefit for this patient population."

Side effects were consistent with those previously seen in LBH589 studies. The most common Grade 3/4 adverse events in the LBH589 combination arm were thrombocytopenia (67% versus 31% with placebo), lymphopenia (53% versus 40% with placebo), neutropenia (35% versus 11% with placebo), diarrhea (26% versus 8% with placebo) and neuropathy (18% versus 15% with placebo)[1]. Adverse events were generally manageable through supportive care and dose reductions[1].

"The majority of people living with multiple myeloma eventually will stop responding to treatment or relapse, which underscores the need for new treatment options," said Alessandro Riva, MD, Global Head, Novartis oncology Development and Medical Affairs. "The PANORAMA-1 results provide strong evidence of the potential impact LBH589 could have for the multiple myeloma community. We are committed to working with regulatory authorities to make this treatment available to patients as soon as possible."

based on the PANORAMA-1 data, in May, LBH589 was granted priority review by the US Food and Drug Administration (FDA) and a regulatory application was submitted to the European Medicines Agency (EMA). Additional global regulatory submissions are underway. FDA priority review status is given to therapies that may offer major advances in treatment[6].

about PANORAMA-1

The PANORAMA-1 (PANobinostat ORAl in Multiple MyelomA) clinical trial is a Phase III randomized, double-blind, placebo-controlled, multicenter global registration trial to evaluate LBH589 in combination with bortezomib and dexamethasone against bortezomib and dexamethasone alone in patients with relapsed or relapsed and refractory multiple myeloma who failed on at least one prior treatment. The study of 768 patients took place in 215 clinical trial sites worldwide. The primary endpoint of the trial was progression-free survival (PFS). Data for overall survival, the key secondary endpoint of the trial, are not yet mature. Other secondary endpoints include overall response rate, duration of response and safety[1].

about LBH589 and its epigenetic role in multiple myeloma

Multiple myeloma is a cancer of the plasma cells, a kind of white blood cell present in bone marrow-the soft, blood-producing tissue that fills the center of most bones. The cancer is caused by the production and growth of abnormal cells within the plasma, which multiply and build up in the bone marrow, pushing out healthy cells and preventing them from functioning normally[7]. Multiple myeloma is an incurable disease with a high rate of relapse (when the cancer returns) and resistance (when the therapy stops working), despite currently available treatments[8]. It typically occurs in individuals 60 years of age or older, with few cases in individuals younger than 40[5].

Epigenetics is the cell programming that governs gene expression and cell development[9]. In multiple myeloma, the normal epigenetic process is disrupted (also called epigenetic dysregulation) resulting in the growth of cancerous plasma cells, potential resistance to current treatment and ultimately disease progression[10],[11].

LBH589 is a potent pan-DAC inhibitor that if approved will be a first-in-class treatment for patients with relapsed or relapsed and refractory multiple myeloma[12]. As an epigenetic regulator, LBH589 may help restore cell programming in multiple myeloma[13].

Because LBH589 is an investigational compound, the safety and efficacy profile has not yet been established. Access to this investigational compound is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. Because of the uncertainty of clinical trials, there is no guarantee that LBH589 will ever be commercially available anywher in the world.

Disclaimer

The foregoing release contains forward-looking statements that can be identified by words such as "offers," "will," "investigational," "increasing," "ultimately," "potential," "committed," "priority review," "underway," "may," "offer," "yet," or similar terms, or by express or implied discussions regarding potential marketing approvals for LBH589, or regarding potential future revenues from LBH589. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that LBH589 will be approved for sale in any market wher it has been submitted, or at any particular time. Neither can there be any guarantee that LBH589 will be submitted or approved for sale in any additional markets, or at any particular time. Nor can there be any guarantee that LBH589 will be commercially successful in the future. In particular, management's expectations regarding LBH589 could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to updat any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

about Novartis

Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 135,000 full-time-equivalent associates and sell products in more than 150 countries around the world. For more information, please visit http://www.novartis.com.

2、礼来糖尿病新药Trulicity获FDA批准

发布日期：2014-09-19 来源：fda

美国礼来 9月18日宣布，公司II类糖尿病新药Trulicity (dulaglutide)正式获得美国食品药品监督管理局（FDA）批准。

　　Trulicity是一种胰高血糖素样肽-1（GLP-1）受体激动剂，每周注射一次，不限时间。该药物适用于正在进行节食和运动的II类糖尿病患者，不适用于I类糖尿病，也不能替代胰岛素。

　　此次获批是基于礼来公司进行的5个大型临床III期研究。数据显示，Trulicity在所有临床试验中的血糖控制表现要优胜于其相对应的安慰剂。

　　礼来表示，公司将会在年底之前上市0.75mg和1.5mg两种剂型，并正在向欧盟和日本药监局提交申请。

　　Trulicity 在获批同时还附带美国FDA的黑框警告，即该药物在小鼠体内试验会加大甲状腺C细胞肿瘤的风险。甲状腺髓样癌患者或II类内分泌腺瘤综合征患者禁用该药。

FDA approves Trulicity to treat type 2 diabetes

The U.S. Food and Drug Administration today approved Trulicity (dulaglutide), a once-weekly subcutaneous injection to improve glycemic control (blood sugar levels), along with diet and exercise, in adults with type 2 diabetes.

Type 2 diabetes affects about 26 million people and accounts for more than 90 percent of diabetes cases diagnosed in the United States. Over time, high blood sugar levels can increase the risk for serious complications, including heart disease, blindness, and nerve and kidney damage.

"Type 2 diabetes is a serious chronic condition that causes blood glucose levels to rise higher than normal,” said Mary Parks, M.D., deputy director of the Office of Drug evaluation II in the FDA’s Center for Drug evaluation and Research. “Trulicity is a new treatment option, which can be used alone or added to existing treatment regimens to control blood sugar levels in the overall management of type 2 diabetes.”

Trulicity is a glucagon-like peptide-1 (GLP-1) receptor agonist, a hormone that helps normalize blood sugar levels. The drug’s safety and effectiveness were evaluated in six clinical trials in which 3,342 patients with type 2 diabetes received Trulicity. Patients receiving Trulicity had an improvement in their blood sugar control as observed with reductions in HbA1c level (hemoglobin A1c is a measure of blood sugar control).

Trulicity has been studied as a stand-alone therapy and in combination with other type 2 diabetes therapies, including metformin, sulfonylurea, thiazolidinedione, and prandial insulin. Trulicity should not be used to treat people with type 1 diabetes; those who have increased ketones in their blood or urine (diabetic ketoacidosis); those with severe stomach or intestinal problems; or as first-line therapy for patients who cannot be managed with diet and exercise.

Trulicity has a boxed warning that tumors of the thyroid gland (thyroid C-cell tumors) have been observed in rodent studies with Trulicity but that it is unknown whether Trulicity causes thyroid C-cell tumors, including a type of thyroid cancer called medullary thyroid carcinoma (MTC), in humans. Trulicity should not be used in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (a disease in which patients have tumors in more than one gland in their body, which predisposes them to MTC).

The FDA is requiring the following post-marketing studies for Trulicity:

· a clinical trial to evaluate dosing, efficacy, and safety in pediatric patients;

· a study to assess potential effects on sexual maturation, reproduction, and CNS development and function in immature rats;

· a medullary thyroid carcinoma (MTC) case registry of at least 15 years duration to identify any increase in MTC incidence related to Trulicity;

· a clinical trial comparing Trulicity with insulin glargine on glycemic control in patients with type 2 diabetes and moderate or severe renal impairment; and

· a cardiovascular outcomes trial to evaluate the cardiovascular risk of Trulicity in patients with high baseline risk of cardiovascular disease.

The FDA approved Trulicity with a Risk evaluation and Mitigation Strategy (REMS), which consists of a communication plan to inform health care professionals about the serious risks associated with Trulicity.

In clinical trials, the most common side effects observed in patients treated with Trulicity were nausea, diarrhea, vomiting, abdominal pain, and decreased appetite.

Trulicity is manufactured by Indianapolis-based Eli Lilly and Company.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

3、勃林格殷格翰投6亿美元进一步挖掘肺癌新药Gilotrif潜力

发布日期：2014-09-19 来源：生物谷

近年来，癌症疫苗研发领域失败案例累累，勃林格殷格翰迎难而上，与CureVac签署6亿美元协议，合作开发肺癌新一代免疫疗法，进一步挖掘肺癌新药Gilotrif的潜力。

-2个多月前，德国生物技术公司CureVac才刚刚与赛诺菲签署2.5亿美元协议，在mRNA疫苗领域进一步强化了合作伙伴关系。近日，CureVac又与勃林格殷格翰（Boehringer Ingelheim）结成联盟，签署6亿美元协议，包括一笔4500万美元的前期款及高达5.56亿美元的里程碑款，勃林格将获得癌症疫苗CV9202的全球商业化权利。

勃林格计划将CV9202与其肺癌一线治疗新药Gilotrif（阿法替尼）配伍，开发新一代免疫疗法，用于非小细胞肺癌（NSCLC）的治疗，同时也计划将CV9202联合化疗/放疗，用于手术不可切除性III期非小细胞肺癌（NSCLC）的治疗。

近年来，癌症疫苗研发领域失败案例累累。最近几个月，该领域中其他数个研发团队也相继失败，着实令人心寒。例如，德国默克的癌症疫苗Stimuvax最近在日本一项临床试验中失败，葛兰素史克（GSK）的癌症疫苗MAGE-3也已积累了一系列的失败案例，Vical公司的ALLovectin和Dendreon公司的Provenge也惨遭淘汰。

不过，CureVac对其独特的mRNA疫苗满怀信心，而勃林格也坚信，该公司的mRNA疫苗技术有望触发强大的免疫反应，并在其他癌症疫苗失败的领域大放光彩。让人不得不佩服其双方的胆识和自信。

CureVac公司一直致力于治疗性癌症疫苗和传统预防性疫苗的开发，用于对抗病毒的传播，这引起了赛诺菲的兴趣。在癌症方面，CureVac创始人坚信，mRNA可被注射入人体，触发靶向肿瘤细胞的特异性免疫反应，该公司在临床中走的最远的是IIb期前列腺癌项目，利用一组6种mRNA分子编码在前列腺癌细胞中过度表达的特异性抗原。CV9202的构建方式与之相同，只是针对非小细胞肺癌（NSCLC）。

勃林格殷格翰肺癌药物Gilotrif（afatanib）于2013年7月获FDA批准，该药是一种酪氨酸激酶抑制剂，作为口服给药的新型一线治疗药物，用于表皮生长因子受体（EGFR）外显子19缺失或外显子21（L858R）替代突变的转移性非小细胞肺癌（NSCLC）患者的治疗。在临床试验中，与安慰剂相比，Gilotrif显著延迟了无进展生存期（PFS，11.1个月 vs 6.9个月）。

很显然，勃林格相信Gilotrif在对抗肺癌方面能做的更好。就像很多其他抗癌药物开发商，勃林格深信，癌症疫苗也可能作为现有疗法的增效剂。因此，勃林格打算与CureVac联手测试该理论。\

英文原文：Boehringer Ingelheim and CureVac announce collaboration to develop next generation lung cancer immunotherapy

HEADLINE2- Boehringer Ingelheim obtains exclusive global rights for development and commercialization of CureVac's investigational therapeutic cancer vaccine CV9202- CV9202 is based on CureVac's RNA technology (RNActive®)- Clinical investigation of CV9202 will be initiated in at least two different lung cancer treatment settings, in combination with Boehringer Ingelheim's afatinib, and in the chemo-radiation therapy setting- The in-licensing of this investigational cancer compound adds an innovative new approach to Boehringer Ingelheim's lung cancer development portfolio

INGELHEIM and TUBINGEN, Germany, and RIDGEFIELD, Conn., Sept. 18, 2014 /PRNewswire/ -- Boehringer Ingelheim and CureVac, leader in mRNA (messenger ribonucleic acid)-based drug development, today jointly announce an exclusive global license and development collaboration. The new collaboration focuses on CureVac's CV9202, a novel investigational therapeutic mRNA vaccine in early clinical development for the treatment of lung cancer. Boehringer Ingelheim will start clinical investigation of CV9202 in at least two different lung cancer settings, in combination with afatinib in patients with advanced or metastatic epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) and in combination with chemo-radiation therapy in patients with unresectable stage III NSCLC. CureVac receives EUR 35 million (approximately $45 million). Further, CureVac can achieve milestone payments of up to EUR 430 million (approximately $556 million) and royalties on sales.

This new agreement is part of Boehringer Ingelheim's long-term commitment to delivering tomorrow's cancer therapies through the discovery of novel treatment options with high therapeutic value for patients. The company's oncology portfolio includes afatinib, a once-daily kinase inhibitor that irreversibly binds and inhibits ErbB1, ErbB2 and ErbB4 receptors and is approved in a number of markets including the EU and US. In the US, afatinib is marketed as Gilotrif® for the first-line treatment of common types of EGFR-mutation positive metastatic NSCLC (Del 19 or L858R). Boehringer Ingelheim's oncology pipeline covers a broad range of solid tumors and hematologic malignancies (blood cancer), including two investigational compounds in Phase III clinical development: nintedanib in NSCLC and colorectal cancer, and volasertib in acute myeloid leukemia. These compounds are not approved, and their safety and efficacy have not been established.

"At Boehringer Ingelheim we are proud of our commitment to help improve the treatment of cancers with a high medical need. In our collaboration with CureVac, we will investigate combining existing treatments with the approach of sustained activation of the immune system. With this we hope to be able to develop new treatments and further expand our broad pipeline in lung cancer," said Professor Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim.

CureVac's mRNA-based technology represents a potential novel approach in cancer treatment. For the first time mRNA could be optimized to mobilize the patient's own immune system to fight the tumor with a specific immune response elicited through the RNActive® vaccine. Cancer immunotherapy has been chosen as the "Breakthrough of the year 2013" by SCIENCE magazine. CV9202 is a combination of mRNA molecules coding for six antigens overexpressed in lung cancer, designed to induce an immune response against the tumor. CV9202 and the preceding RNActive® cancer vaccine CV9201 tested in initial clinical trials by CureVac demonstrated activity in generating immune responses against all anti-tumor antigens.

Ingmar Hoerr, co-founder and CEO of CureVac GmbH commented: "This collaboration is extremely relevant for CureVac because, as a biotech enterprise, we rely on collaboration with strong partners for the clinical development and commercialization of our compounds. Cancer immunotherapy represents one of the biggest innovations in cancer treatment of recent times and we are delighted to now be working with Boehringer Ingelheim. The out-licensing and clinical development of our promising therapeutic vaccine CV9202 represents the logical next step in developing this novel treatment for cancer patients, and the significant commitment from Boehringer Ingelheim underscores the relevance of the mRNA technology."

about CureVac
CureVac, a clinical stage biopharmaceutical company from Tubingen, Germany, is pioneering the field of mRNA-based technology platforms for medical purposes with which mRNA is specifically optimized and formulated. Since 2000 the company develops novel mRNA-based cancer immunotherapies and prophylactic vaccines against infectious diseases – both under the brand RNActive®. CureVac has successfully established the first GMP (good manufacturing practice) facility worldwide for the manufacture of RNA and mRNA and has pioneered mRNA-based drugs in clinical studies.

The company has successfully completed Phase I/IIa clinical studies with its RNActive® cancer vaccines in prostate cancer and non-small cell lung cancer (NSCLC). Results so far have shown that mRNA-based products induced immune responses including humoral and cellular, helper (both Th1 and Th2) and effector and memory responses. CureVac is currently conducting a number of clinical trials with its RNActive® vaccines. A large randomized Phase IIb clinical trial in castrate resistant prostate cancer with CV9104 has been fully enrolled in December 2013. In the field of cancer immunotherapy CureVac is already collaborating with the Ludwig Cancer Research Institute to enable clinical testing of novel cancer immunotherapy treatment options.

CureVac's RNActive® technology is also used to develop prophylactic vaccines for infectious diseases. In March 2014, CureVac received the EUR 2 million Vaccine Prize from the European Commission for its RNActive® vaccine technology. In particular, the jury acknowledged that mRNA-based (RNActive®) vaccines represent a novel technology enabling the development of safe, efficacious and cost-effective vaccines that are protected against elevated temperature as well as inadvertent freezing. In the field of prophylactic vaccines CureVac is amongst others collaborating with Sanofi Pasteur, In-Cell-Art, DARPA and Janssen Pharmaceuticals.

作者: 朵朵7 时间: 2014-9-19 04:12 PM
谢谢楼主分享，看了留个脚印

作者: abbywaiting 时间: 2014-9-19 09:55 PM
什么时候我有这么广的知识面吖

作者: humanwell2012 时间: 2014-9-20 10:04 PM
谢谢楼主分享！

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