葛兰素史克表示，即使美国食品药品监督管理局（FDA）给予其快速审批通道，新疫苗最早也将在2015年之后上市。但公司拒绝透露产品可能上市的具体时间。
葛兰素史克新疫苗是基于含有两种埃博拉病毒基因的黑猩猩腺病毒。在疫苗注入之后，这两种基因能产生一种蛋白质，激活人体免疫系统对抗病毒。该疫苗在灵长类动物试验中反应良好。
与此同时，首例感染埃博拉病毒的美国医疗人员于上周五表示，现在恢复情况良好。他接种的是一种名为Zmapp的试验性单抗，目前也没有正式获得批准。
据世卫组织8月8日数据，埃博拉病毒共感染1779人，致死961人，是该病毒自40年前在非洲首次被发现以来，最为严峻的一次疫情。
2、强生II型糖尿病复方新药INVOKAMET（卡那氟星联合盐酸二甲双胍）获FDA批准发布日期：2014-08-11 来源：cnbc
强生杨森制药 8月8日宣布，美国食品药品监督管理局（FDA）正式批准公司旗下新药INVOKAMET（卡那氟星联合盐酸二甲双胍），适用于II型糖尿病。
卡那氟星（商品名INVOKANA）是一种非胰岛素机制的SGLT2抑制剂。该药于2013年3月获得美国FDA的批准，用于II型糖尿病。而二甲双胍则是II型糖尿病的常用药。
根据强生公司发布的临床III期数据显示，相较二甲双胍和其他用药，INVOKAMET能大幅度降低患者体内的糖化血红蛋白水平。此次临床III期共有4732人参与。
INVOKAMET同时还附带黑框警告，即二甲双胍累积有可能会出现乳酸酸中毒，可致死。患者如果有严重肾功能或属于血液透析治疗阶段，也禁止服用该药物。
U.S. FDA Approves INVOKAMET™ (canagliflozin/metformin HCl) for the Treatment of Adults with Type 2 Diabetes
RARITAN, N.J., Aug. 8, 2014 /PRNewswire/ -- Janssen Pharmaceuticals, Inc. announced today the U.S. Food and Drug Administration (FDA) has approved INVOKAMET™, a fixed-dose therapy combining canagliflozin and metformin hydrochloride in a single tablet, for the treatment of adults with type 2 diabetes. INVOKAMET™ provides the clinical attributes of INVOKANA® (canagliflozin), the first sodium glucose co-transporter 2 (SGLT2) inhibitor available in the United States, together with metformin, which is commonly prescribed early in the treatment of type 2 diabetes. INVOKAMET™ is the first fixed-dose combination of an SGLT2 inhibitor with metformin approved in the United States.
To view the multimedia assets associated with this release, please click: http://www.multivu.com/players/E ... met-type-2-diabetes
"INVOKAMET™ combines, in one tablet, two complementary therapeutic approaches proven effective for managing type 2 diabetes," said Richard Aguilar, M.D.*, Medical Director of Diabetes Nation. "Canagliflozin works with the kidney to promote the loss of glucose in the urine, wheras metformin decreases the production of glucose in the liver and improves the body's response to insulin."
INVOKAMET™ is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled by treatment that includes either canagliflozin or metformin, or who are already being treated with both canagliflozin and metformin as separate medications. INVOKAMET™ should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Study results demonstrated that administration of INVOKAMET™ was equivalent to co-administration of corresponding doses of canagliflozin and metformin as individual tablets.
INVOKAMET™ will be available in tablets containing canagliflozin 50 milligrams (mg) or 150 mg, and metformin 500 mg or 1000 mg. The recommended dosing is twice daily. The prescribing information for INVOKAMET™ also contains a boxed warning for lactic acidosis, a rare, but serious complication that can occur due to metformin accumulation.
"As with INVOKANA®, INVOKAMET™ provides adults with type 2 diabetes an oral therapy that lowers blood sugar and is also associated with reductions in body weight and systolic blood pressure," said Jimmy Ren, Ph.D., Therapeutic Area Lead, metabolics, Medical Affairs, Janssen Pharmaceuticals, Inc. "The available doses of INVOKAMET™ allow physicians to tailor therapy for individual patient needs and offer an alternative for patients who may be able to reduce the number of tablets they take each day."
In March 2013, the FDA approved canagliflozin -- INVOKANA® -- as a single agent, and it is the number-one branded non-insulin type 2 diabetes medication newly prescribed by U.S. endocrinologists.[1] It is also the second most common branded therapy prescribed by primary care physicians when adding or switching therapies in patients.[2] Since its launch, more than one million prescriptions have been written for INVOKANA®.[3]
The co-administration of INVOKANA® and metformin has been studied in six Phase 3 clinical studies that enrolled 4,732 patients with type 2 diabetes. The Phase 3 studies evaluated INVOKANA® in combination with metformin compared to metformin alone or to metformin plus another diabetes therapy. The studies were part of the comprehensive global Phase 3 program for INVOKANA® that enrolled 10,285 patients, one of the largest clinical programs in type 2 diabetes submitted to health authorities to date. The Phase 3 studies showed that the combination of INVOKANA® and metformin lowered blood sugar and, in pre-specified secondary endpoints, was associated with significant reductions in body weight and systolic blood pressure.
In two studies comparing INVOKANA® plus metformin to current standard treatments plus metformin – one studying sitagliptin and the other studying glimepiride – INVOKANA® dosed at 300 mg provided greater reductions in A1C levels and body weight than either comparator. A1C is the percent of red blood cell hemoglobin with glucose attached to it and an indicator of average blood glucose over the previous two to three months. In the two studies, the overall incidence of adverse events was similar with INVOKANA® and the comparators.
Results from the Phase 3 studies showed that the most common adverse events with INVOKANA® are female genital mycotic (fungal) infections, urinary tract infections and increased urination. These specific adverse events were generally mild to moderate in intensity and infrequently led to discontinuation in Phase 3 studies. The most common adverse reactions due to initiation of metformin, as noted in the prescribing information for that medication, are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use. INVOKANA® can increase the risk of hypoglycemia when combined with insulin or a medication that increases insulin levels (e.g., a sulfonylurea). Therefore, a lower dose of insulin or insulin-raising medication may be required to minimize the risk of hypoglycemia when used in combination with INVOKAMET™.
Janssen Pharmaceuticals, Inc. and its affiliates have rights to canagliflozin through a license agreement with Mitsubishi Tanabe Pharma Corporation. Janssen Pharmaceuticals, Inc. and its affiliates have marketing rights in North America, South America, Europe, the Middle East, Africa, Australia, New Zealand and parts of Asia.
On April 25, 2014, Janssen-Cilag International NV announced that the European Commission (EC) approved VOKANAMET® (a fixed-dose therapy combining canagliflozin and immediate release metformin hydrochloride in a single tablet) in the European unio, for the treatment of adults with type 2 diabetes mellitus to improve glycemic control. INVOKANA® is approved as a single agent in Aruba, Australia, Brazil, Canada, Chile, Costa Rica, El Salvador, the European unio (31 countries), Guatemala, Kuwait, Mexico, Peru, Singapore, South Korea, Switzerland, United Arab Emirates, and the United States.
about Type 2 Diabetes
An estimated 371 million people worldwide are living with diabetes[4] and approximately 29 million people have diabetes in the United States.[5] Type 2 diabetes comprises 90 to 95 percent of people with diabetes,[5] which is chronic and affects the body's ability to metabolize sugar (glucose), and is characterized by the inability of pancreatic beta cell function to keep up with the body's demand for insulin.
Nearly half of adults with type 2 diabetes do not achieve recommended levels of glucose control, and if left uncontrolled, type 2 diabetes can lead to serious complications.[6],[7],[8] Improved glycemic control has been demonstrated to reduce the onset and progression of these complications. [9]
WHAT IS INVOKAMET™?
INVOKAMET™ contains two prescription medicines called canagliflozin (INVOKANA®) and metformin hydrochloride (GLUCOPHAGE®). It is used along with diet and exercise to improve blood sugar (glucose) control in adults with type 2 diabetes when treatment with either canagliflozin or metformin, or both medications, has not controlled your blood sugar. INVOKAMET™ is not for people with type 1 diabetes or with diabetic ketoacidosis (increased ketones in blood or urine). It is not known if INVOKAMET™ is safe and effective in children under 18 years of age.
importANT SAFETY INFORMATION
INVOKAMET™ can cause serious side effects, including:
- Lactic Acidosis. Metformin, one of the medicines in INVOKAMET™, can cause a rare but serious condition called lactic acidosis (a build-up of lactic acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital. Stop taking INVOKAMET™ and call your doctor right away if you have any of the following symptoms which could be signs of lactic acidosis: feel very weak or tired; have unusual (not normal) muscle pain; have trouble breathing; have unusual sleepiness or sleep longer than usual; have stomach pains, nausea, or vomiting; feel dizzy or lightheaded; or have a slow/irregular heartbeat
You have a higher chance of getting lactic acidosis with INVOKAMET™ if you have conditions such as: kidney problems, or your kidneys are affected by certain X-ray tests that use injectable dye; liver problems; congestive heart failure; drink alcohol very often, (or drink a lot of alcohol in short-term); get dehydrated; have surgery; have a heart attack, severe infection, or stroke; or are 80 years of age or older and have not had your kidneys tested.
Do not take INVOKAMET™ if you:
- Have severe kidney problems or are on dialysis, have a condition called metabolic acidosis or diabetic ketoacidosis (increased ketones in the blood or urine). Are allergic to canagliflozin, metformin, or any of the ingredients in INVOKAMET™. See the end of the Medication Guide for a list of ingredients in INVOKAMET™. Symptoms of allergic reaction may include: rash; raised red patches on your skin (hives); swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing
Before you take INVOKAMET™, tell your doctor if you: have kidney problems, have liver problems, are on a low sodium (salt) diet, have ever had an allergic reaction to INVOKAMET™, or are going to get an injection of dye or contrast agents for an X-ray procedure (INVOKAMET™ will need to be stopped for a short time); have heart problems (including congestive heart failure); drink alcohol very often (or drink a lot of alcohol in short term); or have any other medical conditions.
Tell your doctor if you are or plan to become pregnant, are breastfeeding or plan to breastfeed. It is not known if INVOKAMET™ will harm your unborn baby. It is also not known if INVOKAMET™ passes into your breast milk.
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take: diuretics (water pills), rifampin (used to treat or prevent tuberculosis), phenytoin or phenobarbital (used to control seizures), ritonavir (Norvir®, Kaletra®, Lopinavir®-used to treat HIV infection), or digoxin (Lanoxin®- used to treat heart problems).
Possible Side Effects of INVOKAMET™
INVOKAMET™ may cause serious side effects, including: dehydration- INVOKAMET™ can cause some people to have dehydration (the loss of body water and salt), kidney problems, a high amount of potassium in your blood (hyperkalemia), liver problems, or low blood sugar (hypoglycemia). If you take INVOKAMET™ with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or insulin may need to be lowered while you take INVOKAMET™.
Signs and symptoms of low blood sugar may include: headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, sweating, shaking or feeling jittery.
Vaginal yeast infection: Women taking INVOKAMET™ may get vaginal yeast infections. Symptoms include: vaginal odor, white or yellowish discharge, or vaginal itching.
Yeast infection of the penis (balanitis or balanoposthitis): Men taking INVOKAMET™ may get a yeast infection of the skin around the penis. Symptoms include: redness, itching, or swelling of the penis; rash; foul smelling discharge; or pain in the skin around penis.
Serious allergic reaction: If you have any symptoms of a serious allergic reaction, stop taking INVOKAMET™ and call your doctor right away or go to the nearest hospital emergency room.
Low vitamin B12 (vitamin B12 deficiency): Using metformin for long periods of time may cause a decrease in the amount of vitamin B12 in your blood. Your doctor may do blood tests to check your levels.
The most common side effects of INVOKAMET™ include: urinary tract infection; changes in urination, including urgent need to urinate more often, in larger amounts, or at night; diarrhea, nausea and vomiting, gas, weakness, indigestion, upset stomach, or headache.
Tell your doctor if you have any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Janssen Scientific Affairs, LLC at 1-800-526-7736.
Please see the full Product Information, including Boxed Warning, and Medication Guide.
WHAT IS INVOKANA®?
INVOKANA® is a prescription medicine used along with diet and exercise to lower blood sugar in adults with type 2 diabetes. INVOKANA® is not for people with type 1 diabetes or with diabetic ketoacidosis (increased ketones in blood or urine). It is not known if INVOKANA® is safe and effective in children under 18 years of age.
importANT SAFETY INFORMATION
INVOKANA® can cause important side effects, including:
- Dehydration (the loss of body water and salt), which may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). You may be at higher risk of dehydration if you have low blood pressure, take medicines to lower your blood pressure (including diuretics [water pills]), are on a low sodium (salt) diet, have kidney problems, or are 65 years of age or older
- Vaginal yeast infection. Women who take INVOKANA® may get vaginal yeast infections. Symptoms include: vaginal odor, white or yellowish vaginal discharge (discharge may be lumpy or look like cottage cheese), or vaginal itching
- Yeast infection of the penis (balanitis or balanoposthitis). Men who take INVOKANA® may get a yeast infection of the skin around the penis. Symptoms include: redness, itching, or swelling of the penis; rash of the penis; foul-smelling discharge from the penis; or pain in the skin around penis
Talk to your doctor about what to do if you get symptoms of a yeast infection of the vagina or penis.
Do not take INVOKANA® if you:
- are allergic to canagliflozin or any of the ingredients in INVOKANA®. Symptoms of allergic reaction may include: rash; raised red patches on your skin (hives); or swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing
- have severe kidney problems or are on dialysis
Before you take INVOKANA®, tell your doctor if you have kidney problems, liver problems, are on a low sodium (salt) diet, ever had an allergic reaction to INVOKANA®, or have other medical conditions.
Tell your doctor if you are or plan to become pregnant, are breastfeeding, or plan to breastfeed. It is not known if INVOKANA® will harm your unborn baby. It is also not known if INVOKANA® passes into your breast milk.
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take diuretics (water pills), rifampin (used to treat or prevent tuberculosis), phenytoin or phenobarbital (used to control seizures), ritonavir (Norvir®, Kaletra®, Lopinavir® - used to treat HIV infection), or digoxin (Lanoxin® - used to treat heart problems).
Possible Side Effects of INVOKANA®
INVOKANA® may cause serious side effects, including: kidney problems, a high amount of potassium in your blood (hyperkalemia), or low blood sugar (hypoglycemia). If you take INVOKANA® with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea medicine or insulin may need to be lowered while you take INVOKANA®.
Signs and symptoms of low blood sugar may include: headache, drowsiness, weakness, dizziness, confusion, irritability, hunger, fast heartbeat, sweating, shaking, or feeling jittery.
Serious allergic reaction. If you have any symptoms of a serious allergic reaction, stop taking INVOKANA® and call your doctor right away or go to the nearest hospital emergency room.
The most common side effects of INVOKANA® include: vaginal yeast infections and yeast infections of the penis; urinary tract infection; or changes in urination, including urgent need to urinate more often, in larger amounts, or at night.
Tell your doctor if you have any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Janssen Scientific Affairs, LLC at 1-800-526-7736.
Please see the full Prescribing Information and Medication Guide.
Canagliflozin is licensed from Mitsubishi Tanabe Pharma Corporation.
Trademarks are those of their respective owners.
about Janssen Pharmaceuticals, Inc.
As a member of the Janssen Pharmaceutical Companies of Johnson & Johnson, Janssen Pharmaceuticals, Inc. is dedicated to addressing and resolving the major unmet medical needs of our time. Driven by our commitment to patients, healthcare professionals, and caregivers, we strive to develop sustainable and integrated healthcare solutions by working in partnership with all stakeholders on the basis of trust and transparency. Our daily work is guided by meeting goals of excellence in quality, innovation, safety, and efficacy in order to advance patient care.
For more information on Janssen Pharmaceuticals, Inc., visit us at www.janssenpharmaceuticalsinc.com or follow us on Twitter at www.twitter.com/JanssenUS and on YouTube at www.Youtube.com/JanssenUS.
*Dr. Aguilar was not associated with the INVOKANA® clinical trials and was not compensated for any media work. He has been a paid consultant to Janssen Pharmaceuticals, Inc.
[1] Data on file. based on NBRx data sourced from IMS NPA Market Dynamics Database, weekly data, showing INVOKANA® has been the leading branded non-insulin type 2 diabetes medication newly prescribed by U.S. endocrinologists for eight weeks, through July 25, 2014, the most recent data available at time of approval of INVOKAMET™.
[2] Data on file. based on NBRx data sourced from IMS NPA Market Dynamics Database, weekly data through July 25, 2014
[3] Data on file. based on total prescription data sourced from IMS NPA National Database, weekly data through July 25, 2014.
[4] International Diabetes Federation, Diabetes Atlas 5th Edition 2012 Update, New estimates for 2012 of diabetes prevalence, mortality, and healthcare expenditures. Available at: http://www.idf.org/sites/default ... Poster_2012_EN.pdf.
[5] Centers for Disease Control and Prevention, National Diabetes Statistics Report, 2014. Available at: http://www.cdc.gov//diabetes/pub ... etes-report-web.pdf
[6] Bailey CJ. Renal glucose reabsorption inhibitors to treat diabetes. Trends Pharmacol Sci. 2011;32(2):63-71.
[7] Casagrande SS, Fradkin JE, Saydah SH, Rust KF, Cowie CC. The prevalence of meeting A1C, blood pressure, and LDL goals among people with diabetes, 1988–2010. Diabetes Care. 2013 Feb 15. Epub ahead of print.
[8] World Health Organization, Media Centre, Diabetes, Fact sheet Number 312. Available at: http://www.who.int/mediacentre/factsheets/fs312/en/. Accessed April 1, 2013.
[9] Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
3、EMA授予Alnylam制药RNAi疗法ALN-AT3孤儿药地位发布日期：2014-08-11 来源：新药汇
EMA授予RNAi靶向疗法ALN-AT3孤儿药地位。年初赛诺菲$7亿购Alnylam股份，8月罗氏$4.5亿收购Santaris，一系列动作表
明，制药巨头重燃热情并已重返RNA靶向研发。
全球领先的RNAi药物开发公司——Alnylam制药8月8日宣布，欧洲药品管理局（EMA）孤儿药品委员会（COMP）已授予RNAi疗法ALN-AT3孤儿药地位，用于A型血有病和B型血友病的治疗。目前，Alnylam正开发ALN-AT3作为一种皮下注射RNAi疗法，靶向抗凝血酶（AT），用于血友病（包括A型血友病、B型血友病、伴有抑制剂的A或B型血友病）及其他罕见出血性疾病（RBD）的治疗。
此前，FDA已于2013年8月授予ALN-AT3治疗A型血友病和B型血友病的孤儿药地位。ALN-AT3采用了Alnylam制药专有的半乳糖胺共轭递送平台（GalNAc-siRNA平台）开发，能够通过皮下注射给药。
临床前数据表明，ALN-AT3能够使凝血酶的生成正常化，并能够改善血友病小鼠的止血，同时还可以完全纠正一种非人类灵长类动物（NHP）血友病"抑制剂"模型中凝血酶的生成。
目前，ALN-AT3正处于I期临床。今年5月在世界血友病联合会2014世界大会上，Alnylam公布了在健康志愿者中开展的研究A部分的积极顶线数据。数据表明，单次低剂量皮下注射ALN-AT3（0.03mg/kg）使抗凝血酶（AT）沉默达28-32%（p＜0.01），使凝血酶生成的峰值取得了统计学意义的显著提高，凝血酶的生成与AT沉默的时间及沉默程度一致。研究中，ALN-AT3的耐受性良好，未出现显著不良事件。根据A部分的积极数据，Alnylam公司已启动B部分研究，预计将于今年年底获得初步临床数据。
今年1月，赛诺菲（Sanofi）扩大与Alnylam的合作，投资7亿美元收购12%股份，支持相关RNAi疗法临床开发。而本月，罗氏耗资4.5亿美元收购Santaris公司，获锁核酸（LNA）平台，继续发力RNA靶向疗法研发。LNA平台是一个创新的RNAi平台，能够克服早期反义RNA技术及siRNA技术的缺陷性，使RNA靶向治疗跨入了一个崭新的时代。这一系列动作表明，制药巨头已对RNA靶向疗法重燃希望，并已重返RNA治疗领域。
关于Alnylam制药
Alnylam是一家生物制药公司，开发基于RNA干扰（RNAi）的新型疗法，该公司开发的GalNAc-siRNA平台在很大程度上客服了RNAi药物输送困难的难题。目前，该公司有多个RNAi疗法处于临床开发，其在研的其他药物还包括：ALN-TTR，开发用于治疗甲状腺素介导的淀粉样变性（ATTR）；ALN-PCS，开发用于治疗严重高胆固醇血症；AlN-HPN，开发用于治疗难治性贫血的治疗。
英文原文：Alnylam Receives Orphan Drug Designations in the European unio for ALN-AT3, an RNAi Therapeutic in Development for the Treatment of Hemophilia
Alnylam Pharmaceuticals, Inc. (ALNY), a leading RNAi therapeutics company, announced today that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) has granted Orphan Drug Designations for ALN-AT3 as an orphan medicinal product for the treatment of hemophilia A and hemophilia B. Alnylam is developing ALN-AT3, a subcutaneously administered RNAi therapeutic targeting antithrombin (AT), for the treatment of hemophilia and other Rare Bleeding Disorders (RBD).
“We are very pleased to have received Orphan Drug Designations from the EMA COMP for ALN-AT3, a key program in our ‘Alnylam 5x15’ product development and commercialization strategy. We believe that our subcutaneously delivered RNAi therapeutic represents an innovative approach for the management of hemophilia and has great potential to make a meaningful impact in the treatment of this often debilitating bleeding disorder,” said Saraswathy (Sara) Nochur, Ph.D., Senior Vice President, Regulatory Affairs and Quality Assurance at Alnylam. “Having announced positive top-line results in adult healthy volunteers earlier this year, we look forward to presenting initial Phase 1 results, including data in hemophilia subjects, later in the year.”
ALN-AT3 is currently being investigated in a multinational Phase 1 trial. At the World Federation of Hemophilia 2014 World Congress held in May, Alnylam presented positive top-line data from Part A of the study performed in adult healthy volunteers. Initial results from the sole dose cohort enrolled (n=4; 3:1, drug:placebo) showed that a single, low subcutaneous ALN-AT3 dose of 0.03 mg/kg resulted in an up to 28-32% knockdown of AT at nadir (p < 0.01 by ANOVA, relative to placebo). This resulted in a statistically significant (p < 0.01) increase in peak thrombin generation, that was temporally associated and consistent with the degree of AT knockdown. ALN-AT3 was found to be well tolerated with no significant adverse events reported. With these data and in light of a dose escalation stopping rule at a 40% level of AT knockdown, the company has transitioned to Part B of the study – an open-label, multi-dose, dose-escalation study enrolling up to 18 people with moderate to severe hemophilia A or B. The primary objective of this part of the study is to evaluate the safety and tolerability of multiple doses, specifically three weekly doses, of subcutaneously administered ALN-AT3 in hemophilia subjects. Secondary objectives include assessment of clinical activity as determined by knockdown of circulating AT levels and increase in thrombin generation at pharmacologic doses of ALN-AT3. In this part of the study, dose escalation will be allowed to proceed beyond the 40% AT knockdown level. The company plans to present initial clinical results, including results in hemophilia subjects from Part B of the study, by the end of the year.
Orphan Drug Designation by the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than five in 10,000 persons in the European unio (EU), and wher no satisfactory treatment is available. In addition to a 10-year period of marketing exclusivity in the EU after product approval, Orphan Drug Designation provides incentives for companies seeking protocol assistance from the EMA during the product development phase, and direct access to centralized marketing authorization.
Alnylam will be discussing its progress with the ALN-AT3 program in an RNAi Roundtable webinar to be held at 9:30 a.m. ET today, and can be accessed by clicking here.
about Hemophilia and Rare Bleeding Disorders
Hemophilias are hereditary disorders caused by genetic deficiencies of various blood clotting factors, resulting in recurrent bleeds into joints, muscles, and other major internal organs. Hemophilia A is defined by loss-of-function mutations in Factor VIII, and there are greater than 40,000 registered patients in the U.S. and E.U. Hemophilia B, defined by loss-of-function mutations in Factor IX, affects greater than 9,500 registered patients in the U.S. and E.U. Other Rare Bleeding Disorders (RBD) are defined by congenital deficiencies of other blood coagulation factors, including Factors II, V, VII, X, and XI, and there are about 1,000 patients worldwide with a severe bleeding phenotype. Standard treatment for hemophilia patients involves replacement of the missing clotting factor either as prophylaxis or on-demand therapy. However, as many as one third of people with severe hemophilia A will develop an antibody to their replacement factor - a very serious complication; these 'inhibitor' patients become refractory to standard replacement therapy. There exists a small subset of hemophilia patients who have co-inherited a prothrombotic mutation, such as Factor V Leiden, antithrombin deficiency, protein C deficiency, and prothrombin G20210A. Hemophilia patients that have co-inherited these prothrombotic mutations are characterized as having a later onset of disease, lower risk of bleeding, and reduced requirements for Factor VIII or Factor IX treatment as part of their disease management. There exists a significant need for novel therapeutics to treat hemophilia patients.
about Antithrombin (AT)
Antithrombin (AT, also known as “antithrombin III” and "SERPINC1") is a liver expressed plasma protein and member of the "serpin" family of proteins that acts as an important endogenous anticoagulant by inactivating Factor Xa and thrombin. AT plays a key role in normal hemostasis, which has evolved to balance the need to control blood loss through clotting with the need to prevent pathologic thrombosis through anticoagulation. In hemophilia, the loss of certain procoagulant factors (Factor VIII and Factor IX, in the case of hemophilia A and B, respectively) results in an imbalance of the hemostatic system toward a bleeding phenotype. In contrast, in thrombophilia (e.g., Factor V Leiden, protein C deficiency, antithrombin deficiency, amongst others), certain mutations result in an imbalance in the hemostatic system toward a thrombotic phenotype. Since co-inheritance of prothrombotic mutations may ameliorate the clinical phenotype in hemophilia, inhibition of AT defines a novel strategy for improving hemostasis.
about RNAi
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
about Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics as genetic medicines, including programs as part of the company's "Alnylam 5x15TM" product strategy. Alnylam's genetic medicine programs are RNAi therapeutics directed toward genetically defined targets for the treatment of serious, life-threatening diseases with limited treatment options for patients and their caregivers. These include: patisiran (ALN-TTR02), an intravenously delivered RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR) in patients with familial amyloidotic polyneuropathy (FAP); ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting TTR for the treatment of ATTR in patients with TTR cardiac amyloidosis, including familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA); ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders (RBD); ALN-CC5, an RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases; ALN-AS1, an RNAi therapeutic targeting aminolevulinic acid synthase-1 (ALAS-1) for the treatment of hepatic porphyrias including acute intermittent porphyria (AIP); ALN-PCS, an RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia; ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 for the treatment of beta-thalassemia and iron-overload disorders; ALN-ANG, an RNAi therapeutic targeting angiopoietin-like 3 (ANGPTL3) for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia; ALN-AC3, an RNAi therapeutic targeting apolipoprotein C-III (apoCIII) for the treatment of hypertriglyceridemia; and other programs yet to be disclosed. As part of its "Alnylam 5x15" strategy, as updated in early 2014, the company expects to have six to seven genetic medicine product candidates in clinical development - including at least two programs in Phase 3 and five to six programs with human proof of concept - by the end of 2015. Alnylam is also developing ALN-HBV, an RNAi therapeutic targeting the hepatitis B virus (HBV) genome for the treatment of HBV infection. The company's demonstrated commitment to RNAi therapeutics has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and Genzyme, a Sanofi company. In March 2014, Alnylam acquired Sirna Therapeutics, a wholly owned subsidiary of Merck. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 200 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, Cell, the New England Journal of Medicine, and The Lancet. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts.
4、卵巢癌新药阿瓦斯汀是15年来首次获澳大利亚政府补贴的相关药品发布日期：2014-08-11 来源：新药汇
据澳大利亚“新快网”8月8日报道，卵巢癌新药阿瓦斯汀是15年来首次获得澳大利亚政府补贴的相关药品，这将为患病人群减轻负担。
据报道，这种药可以抑制肿瘤的增长，现在向被诊断为3阶段或者4阶段卵巢癌的妇女们开放。这些妇女的疾病严重程度在于，手术无法去除所有的癌细胞。
很多妇女此前每个月支付4000澳元(约合人民币2.28万元)治疗该疾病，本周该药物的价格将因为政府的补贴而降至36.9澳元(约合人民币210元)。每一年，澳大利亚有大约1400名妇女被诊断为卵巢癌症，大部分都会在较早的阶段被发现。
仅有43%的被确诊妇女，存活超过5年;在乳腺癌方面，这一比例达到89%。卵巢癌被成为“沉默的杀手”，因为它难以被人发现，直到被发现，癌症已经进入晚期。
卵巢癌专家高(Jeffrey Goh)来自昆士兰大学，他说阿瓦斯汀的使用再加上化疗，能够提高癌症患者的存活率。 这种药物每3周需要通过静脉注射，通过让肿瘤更加饥饿，而实现治疗的目的。它阻止癌细胞借助血管继续扩张。
高博士的很多澳大利亚病人参与了英国对于药品的实验。他说，这是近15年来针对卵巢癌药物的最新补贴。
5、FDA加快审批Tekmira埃博拉治疗药物TKM-EBOLA发布日期：2014-08-11 来源：medscape
Tekmira的埃博拉药物治疗药物TKM-Ebola在Ⅰ期临床试验中因安全问题被叫停，但随着疫情的爆发，FDA已修改其用于患者的临床试验的审批状态，或为治疗带来新的希望。
Tekmira制药公司周四（8月7日）表示，美国食品药品管理局（FDA）已修改了埃博拉试验性治疗药物的审批状态，可能批准其用于患者的治疗。
该公司在声明中称，FDA告知不列颠哥伦比亚省Tekmira的Burnaby，他们已经将药物需要完全临床支持修改为部分临床支持。
Tekmira执行长 Mark Murray说：“我们很高兴FDA考虑了TKM-EBOLA对于感染患者的风险回报。我们在密切关注埃博拉疫情的爆发及其带来的后果，我们希望能通过TKM-EBOLA提供帮助。”
目前爆发的埃博拉疫情已导致西非接近1000人丧生。
世界卫生组织WHO在8月5日称，下周将召集医学伦理学专家开会，考虑扩大试验性埃博拉药物的应用范围。
Tekmira的埃博拉治疗药物是世界范围内三个在猴子的实验中取得喜人结果，但尚未在人体上进行验证的药物之一。
美国加州生物技术公司 Mapp Biopharmaceutical的药物在西非用于两位美国埃博拉感染的医务工作者后其症状得到改善，该公司因此在国际上名声大噪。
Burnaby还透露，Tekmira在上周埃博拉疫情最严重的时候股票飙升40%。尽管Tekmira的治疗药物TKM-EBOLA的人体试验在上月被推迟，并没有影响买进狂潮的到来。
Tekmia的药物仅在少量健康人身上进行过试验。FDA在7月因为安全考虑暂停了该药的临床研究，因为使用最高剂量组的健康人出现免疫应答方面的问题。
但这项临床研究的暂停仅意味着一项特定的试验不能继续，并不影响该公司新的提议获得通过，例如已经感染埃博拉的患者，对于这些人来说，在死亡的风险面前，治疗安全性方面的风险被相对弱化。
FDA上周向路透社透露，在这种情况下，获益风险比将完全改变。任何可能改变风险获益比，使之向更有利的结局方向倾斜的研究都可能更容易获批。
在这种情况下，一个公司有部分临床数据支持，即使在健康人的原始研究被叫停，仍可能在患者中开展新的研究。
在低位反弹后，Tekmira股票继续表现出色，在周四在多伦多股市以$15.61，上涨6.6个百分点完成交易。
信源地址：http://www.medscape.com/viewarticle/829627
6、辉瑞将扩大肺炎球菌疫苗Prevenar 13的适用人群发布日期：2014-08-11 来源：pmlive
欧洲药品监管机构已开始对辉瑞肺炎球菌疫苗Prevenar 13更广泛用于成年人的上市申请进行审评，这款药物的销售峰值可能会在到10亿美元或更多。
欧洲药品监管机构已开始对辉瑞肺炎球菌疫苗Prevenar 13更广泛用于成年人的上市申请进行审评，这款药物的销售峰值可能会在到10亿美元或更多。Prevenar 13作为儿童疫苗的地位已非常牢固，其年销售额大约在40亿美元，但如果获批用于预防成年人社区获得性肺炎(CAP)可能使其销售额有一个大的提升。
这款疫苗已在欧洲获批用于预防成年人侵袭性肺炎链球菌疾病，这种疾病不太常见，但是一种严重的感染疾病。摩根大通分析师认为，Prevenar 13新适应症的批准可能使这款疫苗被普遍推荐用于成年人，这样其销售峰值会增加15亿美元。
辉瑞已向美国提交了一份上市申请，为Prevnar 13的标签增加新的适应症，预期今年9月份FDA会做出是否批准的决定。在此期间，美国免疫接种顾问委员会于下一周对是否推荐扩展该疫苗的标签给出一个意见。
除了美国，其上市申报资料也被欧洲药品管理局(EMA)接受审评，该上市申报资料基于8.5万患者参与的CAPiTA试验结果，结果显示这款疫苗使65岁及以上成年人的社区获得性肺炎发生率降低一半，非侵袭性及侵袭性疾病的发生率均有明显下降低。
辉瑞疫苗研发高级副总裁Emini表示，肺炎球菌肺炎仍然是一个严重的健康问题，导致老年人罹患重大疾病，并有较高死亡率。“CAPiTA研究结果凸显了Prevenar 13预防这一年龄群体时的潜在收益。”
负责辉瑞疫苗业务的Bourla称，Prevenar 13标签的扩展是“一个很好的机会，因为在全球超过65岁的3亿成年人中有明显未满足的需求”。
信源地址：http://www.pmlive.com/pharma_news/pfizer_closes_on_$1bn_label_expansion_for_prevenar_591334
7、罗氏乳腺癌药物Kadcyla因价格高再次被NICE拒绝发布日期：2014-08-11 来源：pmlive
罗氏与英国国家卫生保健优化研究所(NICE)正就NICE拒绝推荐乳腺癌药物Kadcyla (trastuzumab emtansine)纳入NHS进行激烈争吵。
罗氏与英国国家卫生保健优化研究所(NICE)正就NICE拒绝推荐乳腺癌药物Kadcyla (trastuzumab emtansine)纳入NHS进行激烈争吵。NICE坚持认为，“罗氏对乳腺癌新药Kadcyla价格的决定使其不能常规用于NHS，这着实令人失望”。但罗氏予以强烈反驳，称如果使Kadcyla达到NICE成本效益门槛而将其9万欧元的标价削去60%，那这款药物是没有商业可能的。罗氏表示，该公司未通过患者获取计划来降低这款药物成本，它要对NICE的决定进行上诉，并补充称NICE的评估体系不完善。
Kadcyla旨在治疗癌症已扩散至身体其它部位，不能手术切除并对初始治疗停止响应的HER2阳性乳腺癌患者，这款药物在英格兰通过癌症药物基金可以获得。但在今天的最终草案指南中，NICE认为“Kadcyla的高价格让NICE推荐这款药物是不可能的，尽管证据显示这款药物对患者有益”。
对于Kadcyla的效果没有争议，这款药物在临床试验中与目前许可的合并用药相比，可以使HER2阳性乳腺癌妇女的生命额外延长5.8个月。Kadcyla是一款抗体药物偶联物(ADC)，它将罗氏自己的单克隆抗体曲妥珠单抗（赫赛汀）与ImmunoGen的DM1结合在一起，DM1是一种细胞毒载荷，旨在提升其杀死肿瘤细胞的能力。
但这款药物也是自2011年以来被NICE连续拒绝的第八款用于晚期乳腺癌的治疗药物。罗氏产品总经理Dallas称：“就晚期乳腺癌来说，NICE对Kadcyla的拒绝很简单地证明它们目前的体系不完善，不适用，需要进行彻底的改革。
Kadcyla连接技术的开发花费了30年时间，这款药物本身的研发也花了逾15年的时间，该生产商表示称。然而，NICE的Andrew是无情的。“我们真的很失望，罗氏未能证明更多的灵活性来帮助我们做出积极的推荐，我们不会以罗氏提议的价格推荐Kadcyla。”
信源地址：http://www.pmlive.com/pharma_new ... yla_rejected_591184
8、NICE再次更新厄洛替尼与吉非替尼指南发布日期：2014-08-11 来源：firstwordpharma
经过前期协商之后，NICE进一步更新的草案指南于8月7日发布。新的草案指南临时推荐厄洛替尼作为一种治疗选择用于特定情况下经过先前化疗后病情又出现恶化的非小细胞肺癌患者，但另一款癌症药物吉非替尼未得到推荐。
经过前期协商之后，NICE进一步更新的草案指南于8月7日发布。新的草案指南临时推荐厄洛替尼作为一种治疗选择用于特定情况下经过先前化疗后病情又出现恶化的非小细胞肺癌患者，但另一款癌症药物吉非替尼未得到推荐。厄洛替尼与吉非替尼均是EGFR-TKi抑制剂，它们通过阻断信号通路，通过延缓肿瘤增长与扩散而起作用。
在现在的NICE指南中，厄洛替尼通过一项患者获取计划来获得，替代多西他赛作为先前化疗之后的一种二线治疗，但NICE不推荐厄洛替尼用于不适合使用多西他赛的患者。NICE未能推荐吉非替尼用于二线治疗，因为NICE未收到来自生产商的相关证据资料。
自厄洛替尼与吉非替尼最初指南发布以来，临床实践已发生变化。非小细胞肺癌患者在接受一线治疗之前，需要通过诊断检测来确定他们的肿瘤是否发生EGFR突变，以确保医师能够为患者选择最合适的治疗药物。
NICE已推荐这两款药物作为一线治疗用于肿瘤EGFR突变呈阳性的患者。然而，临床专家告诉独立顾问委员会称，在临床实践中，对于已接受厄洛替尼与吉非替尼作为一线治疗的患者来说，在二线治疗中他们不可能再次以EGFR抑制剂来进行治疗，因为肿瘤对这些药物的敏感度已经降低。
在新的草案指南中，厄洛替尼被推荐用于治疗EGFR突变呈阳性得到证实之前使用非靶向化疗药物治疗后病情恶化的患者。厄洛替尼作为一种治疗选择还被推荐用于某些情况下肿瘤EGFR-TK突变未知的患者。
NICE行政长官Dillon对第二次的草案指南评论称：“我们之所以更新推荐，是因为新的证据已经出现，它使我们更好地理解一款药物相对于其成本来说如何能很好地为患者服务。
“这次的草案指南建议推荐厄洛替尼用于之前因肿瘤类型尚未被证实突变呈阳性而接受非靶向化疗治疗的患者。它还推荐厄洛替尼用于仅在某些情况下肿瘤EGFR-TK突变未知的患者。
“对这两款药物正在进行的审查包括厄洛替尼与吉非替尼新的临床及成本效益证据，修订的推荐旨在确保患者能被提供最合适的治疗。临时推荐已经发布并进一步征求公众意见，生产商及其它股东现在有机会对独立评估委员会做出的推荐进行考虑并做出回应。”
信源地址：http://www.firstwordpharma.com/node/1229182?tsid=28®ion_id=3#axzz39lCYdsdn
9、诺和诺德拟于2016年在美国推出新型长效胰岛素Tresiba（德谷胰岛素）发布日期：2014-08-11 来源：reuters
诺和诺德于8月7日表示，该公司可能会于2016年初在美国推出其新型长效胰岛素Tresiba（德谷胰岛素），这款药物是该公司未来的一个关键增长点。
诺和诺德于8月7日表示，该公司可能会于2016年初在美国推出其新型长效胰岛素Tresiba（德谷胰岛素），这款药物是该公司未来的一个关键增长点。在美国FDA因心脏风险而拒绝批准德谷胰岛素及公司同时失去向美国连锁药店进行供货的合同之后，这家全球最大的胰岛素生产商正在为保持强劲利润增长而奋斗。
投资者可能会欢迎看到德谷胰岛素在美国上市的更为详细的时间表。诺和诺德之前曾表示，该公司将于2015年中期有额外的数据就绪，不需要采取进一步的措施。
“他们将德谷胰岛素的数据往前推进了6个月，这对于诺和诺德当然不是无关紧要的。看起来试验研究似乎没有问题，所以这是一个积极的信号，” Alm Brand分析师Jorgensen表示称，该公司对诺和诺德的股票给出“买入”等级。
FDA要求诺和诺德进行额外的试验，而该公司现在称试验在今年底或明年初将会完成，这样诺和诺德可以在2015年上半年提交一份数据分析。“在最好的情况系啊，今年底可能会看到这款药物获得批准，意味着其2016年初可以投放市场，”诺和诺德董事长Sorensen在电话中对新闻记者称。
他说，此前该公司公布了第二季度的业绩，结果与分析师的预期相一致，保持了2014年 7-10%销售增长及大约10%营业利润增长的预测。该公司表示，第二季度的营业利润与85.6亿丹麦克朗预期值相比出现增长，达到87.3亿克朗（15.7亿美元），销售收入为216.3亿克朗，一致预测为217亿克朗。
美国定价压力
由于仿制药的竞争及更广泛的定价压力，诺和诺德在其最大市场美国一直处于压力之中。去年，该公司失去两份向Express scripts控股公司供货的合同，这代表失去大约4000万至4500万的美国客户。
利拉鲁肽用于自身仍能产生一些胰岛素的2型糖尿病患者，这款药物的销售在北美上涨了15%，同时诺和诺德在GLP-1领域将市场份额从65%增加到了69%。但利拉鲁肽因失去Express script合同而受到影响，它的销售增长不能令所有分析师满意，包括来自北欧银行与贝伦堡银行的分析师。
“利拉鲁肽销售额低于一致预测3%，GLP-1市场增长率继续承受压力。这类药物目前正面临来自口服药物更为严峻的竞争，如DPP-IV类药物和SGLT-2抑制剂，” 贝伦堡银行分析师Campbell在一份报告中如此称。
Sorensen认为，美国市场对诺和诺德来说是一个挑战，因为之前赛诺菲与礼来均报道其糖尿病业务出现增长。“很明显，发生在2013年底的情况在2014年还在持续，几乎所有领域都存在增加的定价压力，” Sorensen表示称。今年到目前为止，诺和诺德股价上涨逾28%，超过赛诺菲3%和礼来20%的上涨。
信源地址：http://www.reuters.com/article/2 ... USKBN0G711620140807
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10、欧盟批准辉瑞关节炎药物依那西普nr-axSpA新适应症
辉瑞重磅炸弹级关节炎药物依那西普(Etanercept)在欧洲赢得一项新的适应症，用于治疗早期炎性关节疾病。
辉瑞重磅炸弹级关节炎药物依那西普 (Etanercept) 在欧洲赢得一项新的适应症，用于治疗早期炎性关节疾病。欧盟委员会批准依那西普标签扩展，许可其用于严重中轴脊柱关节炎 (nr-axSpA) 成人患者。
依那西普是去年全球第三大最畅销药物，其最新适应症使这款药物与其竞争对手 TNF 抑制剂阿达木单抗及赛妥珠单抗站在了同一起跑线，而与英利昔单抗相比稍占优势。
活动性中轴性脊柱关节炎（axSpA）是一种疼痛的、渐进型关节炎。据估计，axSpA 影响着千分之三到百分之一的成年人，高达百分之十二的慢性终生炎性疾病 nr-axSpA 患者两年内将进展到更为严重的强直性脊柱炎。
辉瑞在英国的医学总监 Phillips 博士称，“这次新适应症的许可反映了辉瑞继续致力于加强关节炎疾病科学理解，并为患者提供治疗选择以解决这一未满足需求的承诺。”
欧盟委员会的批准决定基于 1031 研究数据，该研究显示 32.4% 的依那西普治疗患者表现出明显的改善，相比之下，安慰剂治疗患者只有 15.7%。依那西普治疗组与安慰剂治疗组报道的与治疗相关的不良事件发生率分别为 57% 和 45%。
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