Janssen-Cilag International NV（杨森）宣布，该公司坎格列净（canagliflozin）/二甲双胍固定剂量复方药（商品名Vokanamet）已获得欧盟批准用于治疗2型糖尿病。
这种复方制剂是每日服用2次的单一片剂，已在今年2月得到欧洲人用医疗产品委员会(CHMP)的推荐应用。该药适用于有以下情况的18岁以上成人2型糖尿病患者，改善其血糖控制：
二甲双胍单药治疗已达最大耐受剂量但仍不能充分控制血糖的患者；
最大耐受剂量二甲双胍联合其他口服降糖药物或胰岛素治疗仍不能充分控制血糖的患者；
正在接受坎格列净片和二甲双胍片两种药物联合治疗的患者。
该药有4种不同的坎格列净/二甲双胍剂量组合：50 mg/850 mg、50 mg/1000 mg, 150 mg/850 mg和 150 mg/1000 mg。这两种组分的降糖机制不同，坎格列净是一种新型的钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂，通过抑制肾脏对葡萄糖的重吸收，增加葡萄糖排泄，进而降低糖尿病患者已升高的血糖水平。而二甲双胍的机制是抑制肝脏葡萄糖生成。
坎格列净（商品名Invokana）已获得美国FDA批准上市，但坎格列净/二甲双胍复方药的上市申请已于今年1月遭到FDA拒绝，FDA要求制药商提供更多数据。
已在欧洲获批上市的SGLT2抑制剂/二甲双胍复方产品还包括达格列净（dapagliflozin）/二甲双胍复方药（商品名Xigduo ，阿斯利康/施贵宝）。
VOKANAMET® (canagliflozin and immediate release metformin hydrochloride fixed dose combination) approved in the European Union for treatment of adults with type 2 diabetes [1]
BEERSE, April 25 2014 – Janssen-Cilag International NV (Janssen) announced today that the European Commission (EC) has approved VOKANAMET® (a fixed-dose therapy combining canagliflozin and immediate release metformin hydrochloride in a single tablet) in the European Union, for the treatment of adults with type 2 diabetes mellitus to improve glycaemic control.[1] Canagliflozin as a single agent was approved as INVOKANA® in the European Union in November 2013.[2]
This EC decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), recommending the approval of canagliflozin and immediate release metformin hydrochloride fixed dose combination therapy, in February 2014. The combination therapy, which is taken as a single pill twice daily, is indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control in:
•patients not adequately controlled on their maximally tolerated doses of metformin alone;[1]
•patients on their maximally tolerated doses of metformin along with other glucose‑lowering medicinal products including insulin, when these do not provide adequate glycaemic control;[1]
•patients already being treated with the combination of canagliflozin and metformin as separate tablets;[1]
Professor Guntram Schernthaner, Department of Medicine I, Rudolfstiftung Hospital, Austria comments, “The approval of VOKANAMET® in the European Union is very welcome news for the growing number of people with type 2 diabetes in this region. Many patients struggle to achieve and maintain long-term glycaemic control, and the introduction of VOKANAMET® provides added convenience to diabetes management, particularly to those patients who may benefit from two diabetes medications in one tablet.”
Commenting on the approval, Jane Griffiths, Company Group Chairman, Janssen Europe, Middle East, and Africa said, “We are delighted that the European Commission has approved VOKANAMET® for use in the European Union, recognising the value and the convenience that this combined treatment option provides for patients. This approval further reinforces Janssen’s ongoing commitment to provide new therapeutic options that help to address unmet needs in the treatment of type 2 diabetes.”
The EC approval of this fixed-dose therapy combining canagliflozin and immediate release metformin hydrochloride in a single tablet taken twice daily was based on significant portions of the comprehensive global Phase 3 clinical development programme for canagliflozin single agent, including the studies with co-administration of metformin and canagliflozin as individual tablets.
The Phase 3 programme evaluated the safety and efficacy of canagliflozin across the spectrum of type 2 diabetes and included placebo and active comparator controlled studies. Three studies have compared canagliflozin to current standard treatments,[3-5] two of which compared canagliflozin to sitagliptin as dual therapy with metformin and the other as triple therapy with metformin and sulphonylurea[3,4]. In addition there is a study comparing canagliflozin to glimepiride as dual therapy with metformin.[5] The Phase 3 programme also included two large studies in special populations:[6-7] patients over age 55 with type 2 diabetes[6] and patients with type 2 diabetes who were considered to be at high risk for cardiovascular disease.[7]
Single agent canagliflozin (INVOKANA®) was approved in the US in March 2013, and in the European Union, as well as Norway, Liechtenstein and Iceland in November 2013.[2]
Canagliflozin is a member of a new class of drugs known as sodium glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors contribute to controlling blood glucose levels via the kidney. As glucose is filtered from the blood into the kidneys, it is reabsorbed back into the bloodstream. An important transport carrier in the renal proximal tubule responsible for this reabsorption is called sodium glucose co-transporter 2 (SGLT2). Canagliflozin selectively inhibits SGLT2, and, as a result, promotes the loss of glucose via the urine, lowering blood glucose levels in adults with type 2 diabetes. This mechanism of action is independent of insulin.[2]
Metformin is a first-line pharmacotherapy that can be used alone or with other medications, including insulin, to treat type 2 diabetes. In people with type 2 diabetes, the liver overproduces glucose, which increases blood glucose levels. Metformin lowers blood glucose levels by decreasing the amount of glucose made by the liver, increasing insulin sensitivity in the muscle and delaying intestinal glucose absorption.[8]
Janssen and its affiliates have rights to canagliflozin through a license agreement with Mitsubishi Tanabe Pharma Corporation. Janssen and its affiliates have marketing rights in North America, South America, Europe, the Middle East, Africa, Australia, New Zealand and parts of Asia.
About Type 2 Diabetes
Type 2 diabetes is a chronic condition that affects the body’s ability to metabolise sugar, or glucose, and is characterised by the inability of pancreatic beta cell function to keep up with the body’s demand for insulin.[9]
The International Diabetes Federation estimates that, in 2013, 382 million people globally were living with diabetes (type 1 and 2), and this diabetes population is expected to grow to over 592 million by 2035. In 2013, it was estimated that over 56 million people were living with diabetes in Europe.[10] The World Health Organisation estimates that 90% of the diabetes population have type 2 diabetes.[11]
If left uncontrolled, type 2 diabetes can lead to serious long-term microvascular and macrovascular complications. Improved glycemic control has been demonstrated to reduce the onset and progression of these complications.
About Janssen
The Janssen Pharmaceutical Companies of Johnson & Johnson are dedicated to addressing and solving the most important unmet medical needs of our time, including oncology, immunology, neuroscience, infectious disease, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world.
More information can be found at www.janssen-emea.com
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995.  The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events.  If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen-Cilag International NV and/or Johnson & Johnson.  Risks and uncertainties include, but are not limited to: economic factors, such as interest rate and currency exchange rate fluctuations; competition, including technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; challenges to patents; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; general industry conditions including trends toward health care cost containment; and increased scrutiny of the health care industry by government agencies.  A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 29, 2013, including in Exhibit 99 thereto, and our subsequent filings with the Securities and Exchange Commission.  Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson.  Neither Janssen-Cilag International NV nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
Information
Generic Name: canagliflozin + metformin IR 
Trade Name: Vokanamet 
Entry Type: New formulation  
Developmental Status
UK: Approved (Licensed) 
EU: Approved (Licensed) 
US: Not recommended for approval (Negative opinion) 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Apr 14: The European Commission has approved VOKANAMET® (a fixed-dose therapy combining canagliflozin and immediate release metformin hydrochloride) in the EU, for the treatment of adults with type 2 diabetes mellitus to improve glycaemic control [8]. 
19/06/2014 14:51:02
Feb 14: Johnson & Johnson submit a response to the FDA [9].
19/06/2014 14:50:50
Feb 14: Positive opinion granted in the EU for the treatment type 2 diabetes mellitus [7]
22/02/2014 18:15:48
Dec 13: The FDA has issued a complete response letter for a fixed-dose combination of canagliflozin and immediate-release metformin to treat adults with T2DM. The letter asks for additional information to support the comparability of the twice-daily dosing regimen of canagliflozin as part of the canagliflozin and metformin combination and the once-daily dosing of canagliflozin as a single agent. Janssen believes it can supply this information based on available clinical data [6].
13/12/2013 13:41:35
Mar 13: Filed in EU Mar 13 [5]
26/03/2013 14:44:39
Dec 12: New Drug Application submitted to US FDA [4]
13/12/2012 12:05:23
PIII in EU & US [1].
06/12/2011 16:02:22
Trial or other data
Apr 12: No further update.
19/04/2012 14:18:16
Four PI studies in healthy volunteers started in 4Q 11: NCT01454622 is eva luating the bioequivalence of canagliflozin/metformin immediate-release vs. the individual components in 64 US subjects from the US; NCT01459094 is an open-label crossover study comparing the bioavailability of canagliflozin/metformin IR when given with or without food in 24 US volunteers; NCT01463774 is comparing fixed-dose canagliflozin/metformin to separate canagliflozin & metformin in 64 US subjects; NCT01463228 is assessing the bioequivalence of the fixed-dose combination vs. individual components in 64 US individuals [2].
07/12/2011 10:30:27
Evidence Based eva luations
EPAR  http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002656/WC500166672.pdf
References  
Available only to registered users
 Category
BNF Category: Other antidiabetics (06.01.02.03)
Pharmacology: Selective sodium glucose co-transporter type 2 (SGLT2) inhibitor plus biguanide, metformin  
Epidemiology: Over 5% of men & 4% of women in England have diagnosed diabetes, & it has been estimated that 3.1% of men & 1.5% of women aged 35 and over have undiagnosed diabetes (85% type 2) [3].  
Indication: Type 2 diabetes mellitus 
Method(s) of Administration  
Oral 
Company Information
Name: Janssen-Cilag 
US Name: Scios 
NICE Information
In timetable: No  
When:  
PBR Likely Healthcare Resource Group included.  
Service
Implications Available only to registered users
Prescribing
Outlook: Available only to registered users
Name Vokanamet
Agency product number EMEA/H/C/002656
Active substance canagliflozin / metformin hydrochloride
International non-proprietary name (INN) or common name canagliflozin / metformin
Therapeutic area Diabetes Mellitus, Type 2
Anatomical therapeutic chemical (ATC) code A10BD16
Publication details
Publication details for Vokanamet Marketing-authorisation holder Janssen-Cilag International N.V.
Revision 0
Date of issue of marketing authorisation valid throughout the European Union 23/04/2014
Contact address:
Janssen-Cilag International N.V.
Turnhoutseweg 30
B-2340 Beerse
Belgium
Vokanamet : EPAR - Product Information
Vokanamet : EPAR - All Authorised presentations
Name Language First published Last updated
Vokanamet : EPAR - Public assessment report (English only) 15/05/2014   
CHMP summary of positive opinion for Vokanamet (English only) 21/02/2014 02/04/2014 
Name Language First published Last updated
Vokanamet : EPAR - Summary for the public Select a language to view the document
   15/05/2014   
Name Language First published Last updated
Vokanamet : EPAR - Risk-management-plan summary