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Eperzan is indicated for the treatment of type 2 diabetes mellitus in adults to improve glycaemic control as:
Monotherapy
When diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to contraindications or intolerance.
Add-on combination therapy
In combination with other glucose-lowering medicinal products including basal insulin, when these, together with diet and exercise, do not provide adequate glycaemic control.
Eperzan Generic Name
Albiglutide
Eperzan(R) (Albiglutid)
| Name |
Eperzan |
| INN or common name |
albiglutide |
| Therapeutic area |
Diabetes Mellitus, Type 2 |
| Active substance |
albiglutide |
| Date opinion adopted |
23/01/2014 |
| Company name |
GlaxoSmithKline Trading Services |
| Status |
Positive |
| Application type |
Initial authorisation |
欧盟委员会已授予葛兰素史克公司糖尿病治疗新药Eperzan（Albiglutide）上市许可，该药将与礼来公司的Bydureon（Exenatide，艾塞那肽）狭路相逢。
Eperzan与Bydureon这两种GLP-1受体激动剂都是相对较新类型的每周注射一次的缓释制剂，旨在帮助使用口服药、短效和长效胰岛素产品失败的患者降低血糖水平（HbA 1c）。
Eperzan适用于依靠节制饮食和运动不能控制血糖水平而又不能使用二甲双胍的II型糖尿病成人患者作为单一治疗药。
它也可被用作与其它降糖药如基础胰岛素联合治疗的附加药物。
葛兰素史克还在等待美国FDA的最终决定，Eperzan被延期三个月审批，预期在4月15日得出结论。
2013年1月和3月，葛兰素史克先后向FDA和欧洲药品局提出申请，计划在几年第三季度在欧盟几个国家上市，随后扩大市场。
欧盟的这一决定基于一项名为Harmony的计划结果。
Albiglutid (Eperzan®), ein neuer GLP-1-Agonist bei Diabetes Typ 2
Rubrik: Drugs
Mit Albiglutid (Eperzan®, Fertigpen à 30mg und 50mg) erhielt ein neuer GLP-1-Agonist die Zulassung von Swissmedic. Der subkutan applizierte Wirkstoff wird sowohl als Monotherapie als auch in Kombination mit anderen blutzuckersenkenden Wirkstoffen, einschliesslich Basalinsulin, eingesetzt. Der genaue Markteinführungstermin ist noch nicht bekannt. Eperzan® ist bereits in Deutschland erhältlich. In der Schweiz sind mit Exenatid (Byetta®, Bydureon®) und Liraglutid (Victoza®) bereits zwei Vertreter dieser Wirkstoffgruppe im Handel.
Albiglutid ist ein so genanntes Fusionsprotein. Es besteht aus zwei an Humanalbumin gekoppelten Aminosäuresequenzen von modifiziertem humanem GLP-1. Aufgrund dieser Struktur ist die Eliminationshalbwertszeit im Vergleich mit GLP-1 oder anderen GLP-1-Agonisten sehr lang und beträgt ca. 5 Tage. Dies ermöglicht wiederum eine einmal wöchentliche, subkutane Injektion.
Die empfohlene Dosis beträgt 30 mg einmal wöchentlich subkutan im Bereich von Bauch, Oberschenkel oder Oberarm-Aussenseite. Bei Bedarf kann die Dosis auf 50 mg erhöht werden. Um das Hypoglykämierisiko zu senken, muss unter Umständen die Dosis von gleichzeitig verabreichten Sulfonylharnstoffen oder Insulin reduziert werden.
Als häufigste Nebenwirkungen werden Durchfall und Übelkeit beobachtet, was für alle GLP-1-Agonisten typisch ist. Zusätzlich kommt es sehr häufig zu Reaktionen an der Injektionsstelle.
Die Anwendung von GLP-1-Agonisten ist mit einem Risiko für eine akute Pankreatitis verbunden. Die Patienten müssen die typischen Symptome wie anhaltende, starke Bauchschmerzen kennen, damit allenfalls die Therapie sofort abgebrochen werden kann.
Da Albiglutid die Magentleerung verzögert, ist bei gleichzeitiger Behandlung mit Wirkstoffen mit enger therapeutischer Breite Vorsicht geboten.
New Drugs Online Report for albiglutide
Information
Generic Name: albiglutide
Trade Name: Eperzan (EU); Tanzeum (US)
Synonym: Syncria
Entry Type: New molecular entity
Developmental Status
UK: Approved (Licensed)
EU: Approved (Licensed)
US: Approved (Licensed)
UK launch Plans: Available only to registered users
Actual UK launch date:
Comments
Aug 14: UK launch planned for 2015 [24].
04/08/2014 10:01:50
Apr 14: Approved in the US to improve glycaemic control as monotherapy or with other hypoglycaemics, along with diet and exercise, in adults with T2DM. The product will carry a boxed warning indicating that thyroid C-cell tumours have been observed in rodent studies with some GLP-1 receptor agonists, although it is unknown whether Tanzeum causes such tumours. The FDA has also requested post-marketing studies, including a trial to assess the drug´s safety, efficacy and dosing in paediatric patients, as well as a cardiovascular outcomes study in patients with a high baseline risk of cardiovascular disease [20].
16/04/2014 08:56:44
Mar 14: Approved in the EU. Eperzan will be launched in several countries in Europe in the third and fourth quarters. The US FDA is due to deliver its verdict on the drug by April 15 [19].
27/03/2014 11:30:46
Jan 14: EU positive opinion for albiglutide for treatment of T2DM in adults to improve glycaemic control as monotherapy (when diet and exercise alone do not provide adequate glycaemic control in pts for whom use of metformin is considered inappropriate due to contraindications or intolerance) or as add-on combination therapy (in combination with other glucose-lowering medicinal products including basal insulin, when these, together with diet and exercise, do not provide adequate glycaemic control) [17].
24/01/2014 15:14:01
Aug 13: The FDA has delayed a decision on approval until 15 April 2014 [16].
03/08/2013 18:24:42
Mar 13: Filed in the EU [14].
07/03/2013 17:54:29
Jan 13: Filed in US [13]
15/01/2013 08:20:18
Jul 12: Filings planned for early 2013 [12].
13/07/2012 10:28:43
Feb 10: Enrolment complete for first 5 studies [7].
06/02/2010 15:38:23
Trial or other data
Jul 14: PIII study published in Diabetes Care. HbA1c change from baseline at week 26 was significantly greater for albiglutide than sitagliptin (−0.83% vs. −0.52%, P = 0.0003). Decreases in HbA1c, FPG, and weight were seen through week 52. Time to hyperglycemic rescue through week 52 was significantly longer for albiglutide than sitagliptin (P = 0.0017). Results of safety assessments were similar between groups, and most adverse events (AEs) were mild or moderate. The incidences of gastrointestinal AEs for albiglutide and sitagliptin were as follows: overall, 31.7%, 25.2%; diarrhea, 10%, 6.5%; nausea, 4.8%, 3.3%; and vomiting, 1.6%, 1.2%, respectively [23].
23/07/2014 09:03:41
Jun 14: Harmony 3 published in Diabetes Care. Added to metformin, at week 104, albiglutide significantly reduced HbA1c compared with placebo (−0.9% [−9.8 mmol/mol]; P < 0.0001), sitagliptin (−0.4% [−4.4 mmol/mol]; P = 0.0001), and glimepiride (−0.3% [−3.3 mmol/mol]; P = 0.0033). Outcomes for FPG and HbA1c were similar [22].
09/06/2014 16:40:44
Jun 14: Harmony 6 published in Diabetes Care. At week 26, HbA1c decreased from baseline by −0.82 ± SE 0.06% (9.0 mmol/mol) with albiglutide and −0.66 ± 0.06% (7.2 mmol/mol) with lispro; treatment difference, −0.16% (95% CI −0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased with albiglutide but increased with lispro (−0.73 ± 0.19 kg vs. +0.81 ± 0.19 kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44 to 51 IU (lispro). Adverse events for albiglutide versus lispro included severe hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs. 29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site reactions (9.5% vs. 5.3%) [21].
09/06/2014 16:39:54
Feb 14: PIII Harmony 3 study published in The Lancet [18].
07/02/2014 10:06:26
Jun 13: In the PIII Harmony 3 study reported at ADA, patients on albiglutide + metformin had greater reductions in blood sugar than those on Januvia or Amaryl but increased gastrointestinal side effects [14].
25/06/2013 16:24:54
Jul 12: A meta-analysis looking at cardiovascular outcomes is required by the FDA and EMA. An independent clinical endpoints committee has adjudicated cardiovascular events across all 8 PIII Harmony studies involving approximately 5,000 patients and from one PII study for the albiglutide meta-analysis. The analysis rules out excess cardiovascular risk according to a threshold pre-specified by the FDA [12].
13/07/2012 10:43:19
Jul 12: Topline results reported from the PIII Harmony 8. The study enrolled 507 patients with mild, moderate and severe renal impairment (GFR of ≥ 15 and < 90 mL/min/1.73m2) and randomised them to albiglutide (30mg weekly with up-titration to 50mg weekly based on glycaemic response) plus placebo, or sitagliptin (25 to 100mg depending on degree of renal insufficiency) plus placebo. Patients were treated for 52 weeks. At the 26-week primary endpoint, albiglutide showed clinically and statistically significant reductions in HbA1c from baseline (8.08% for albiglutide and 8.22% for sitagliptin) and superiority vs sitagliptin (reduction of 0.83% vs 0.52%; p<0.0001 for non-inferiority and p=0.0003 for superiority). Weight loss was significantly greater in the albiglutide group (-0.79kg vs -0.19kg; p=0.0281). During the full 52-week treatment period, albiglutide was generally well tolerated with diarrhoea being the most common adverse event (10% vs 6.5%). Rates for nausea were 4.8% vs. 3.3% and for vomiting 1.6% vs. 1.2%) [12].
13/07/2012 10:43:09
Jun 12: 1-year results from the Harmony 6 study reported at the American Diabetes Association Meeting. The effect on HbA1c seen at 26 weeks (primary endpoint) was maintained at 52 weeks (reduction from baseline of 1.01% with albiglutide vs 0.85% insulin Lispro; p=NS). The proportion of patients achieving a clinically meaningful HbA1c target level (ADA goal of <7.0%) by week 52 was 45% vs 30% (p=NS for treatment difference). Weight changes from baseline were also sustained at 52 weeks (-0.96kg vs +1.66kg; p<0.0001 for treatment difference). Fasting plasma glucose (FPG) decreased from baseline in both study arms throughout the 52 week period (-27mg/dL vs -16mg/dL; p =0.0281 for treatment difference). Adverse events were higher in the albiglutide arm; the most common was nausea (13% vs 2%), diarrhoea (14% vs 6%), and injection site reactions (10% vs 5%). No severe hypoglycaemic events were reported for albiglutide (1% for Lispro) and minor hypoglycaemia (≤70mg/dL) was higher in the Lispro arm vs albiglutide arm (39% vs 23%) [11].
11/06/2012 21:16:18
Apr 12: Topline results have been received from 7 of the 8 ‘Harmony’ PIII studies in T2DM. Results from Harmony 7 were reported in Nov 11. In Harmony 6, the second of the PIII studies to complete, albiglutide was non-inferior to preprandial insulin lispro, each given with insulin glargine, in reducing HbA1c from baseline after 26 weeks of treatment (primary endpoint; 0.82% vs 0.66%, respectively, p<0.0001 for non-inferiority ). Weight change from baseline was -0.73kg vs +0.81kg (p<0.0001 for treatment difference). GI AEs occurred more frequently in the albiglutide arm (13% vs 2.1%) and vomiting (7% vs 1.4%) over the 52 weeks of the study. The company report that primary endpoint 1 and 2-year data from studies Harmony 1 to 5 have been received but as the blinded studies are on-going these data have to remain confidential to protect integrity. However, the company has stated that individual study data are broadly aligned with the results of the two completed studies, and will be used for regulatory filings. Harmony 8 will complete in mid 2012 and the five on-going studies will complete in early 2013. The studies will provide data on the effect of albiglutide over three years. A meta-analysis of cardiovascular safety data will be required to complete the registration package, consistent with FDA guidelines [10].
04/04/2012 11:20:42
Nov 11: In the Harmony 7 study the once-weekly albiglutide did not meet its primary endpoint in a non-inferiority study against once-daily liraglutide. The trial results showed a reduction in blood sugar level (HbA1c) of 0.78% for patients receiving albiglutide vs. a higher reduction of 0.99% for the liraglutide arm. While albiglutide did demonstrate a statistically significant reduction in HbA1c from baseline, it did not meet the primary endpoint of non-inferiority to liraglutide. [9]
17/11/2011 09:24:14
Apr 10: A PIII randomized, double-blind, active-controlled, parallel-group, multicentre study (NCT01098539) started Apr 10 and is expected to complete Aug 12. The study will investigate the efficacy and safety of albiglutide (by weekly subcutaneous injection) vs sitagliptin in 600 subjects wit T2DM with renal impairment. The primary endpoint is change in HbA1c from baseline at 26 weeks [9].
06/04/2010 09:14:36
Jun 09: Results from a PII trial were presented at the annual meeting of the American Diabetes Association. They showed Syncria was more effective than twice-daily exenatide in lowering blood suga, although a spokesman for Lilly and Amylin said the exenatide data were inconsistent with results from previous published trials. Analysits were ‘underwhelmed’ by the data – the absolute reduction in HbA1C was small and weight loss was modest (5).
09/06/2009 08:46:08
March 09: First dosings in PIII trial. (4)
18/03/2009 16:51:21
Feb 09: First patient enrolled in PIII clinical trial programme to evaluate the efficacy, safety and tolerability albiglutide as mono- and add-on therapy in men and women with type 2 diabetes. The PIII programme will include more than 4,000 patients in 5 studies starting early 2009. The primary efficacy endpoint for all studies will be the change from baseline in HbA1c vs placebo and/or active comparators including metformin, sulphonylureas, glitazones, insulin and a dipeptidyl peptidase four inhibitors. The study duration is expected to be two to three years and the main dose and regimen for the programme will be 30 mg weekly (3).
17/02/2009 22:01:16
May 2007, GlaxoSmithKline commenced a phase IIb, randomised, double-blind, placebo-controlled study, where approximately 318 patients with type 2 diabetes will receive albiglutide or the reference agent exenatide (Byetta®, Amylin) for 16 weeks with additional 10 weeks of follow-up. This out-patient study will evaluate the safety and efficacy of albiglutide in patients who are either not taking diabetes medications or who are taking metformin only. Results from the phase IIb study and GlaxoSmithKline´s decision on the possible phase III development of albiglutide are expected in 2008 (2)
13/11/2008 11:44:13
Evidence Based Evaluations
EPAR
References
Available only to registered users
Category
BNF Category: Other antidiabetics (06.01.02.03)
Pharmacology: Once-weekly glucagon-like peptide 1 (GLP 1) receptor agonist. The first drug to fuse human GLP-1 to human albumin.
Epidemiology: In the UK 3.5% of the population has diabetes. (6)
Indication: Type 2 diabetes mellitus
Additional Details:
Method(s) of Administration
Subcutaneous
Company Information
Name: GlaxoSmithKline
US Name: GlaxoSmithKline
NICE Information
Anticipated Commissioning route (England) -
In timetable: - |
