| Information |
Generic Name: |
exenatide
|
| Trade Name: |
Bydureon |
| Entry Type: |
New formulation |
| |
| Developmental Status |
| UK: |
Launched |
| EU: |
Launched |
| US: |
Launched |
| UK launch Plans: |
Available only to registered users |
| Actual UK launch date: |
01/07/2011 |
| Comments |
Feb 12: Launched in US [34].
15/02/2012 10:18:25 |
Jan 12: FDA has approved Bydureon as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes in multiple clinical settings [33]
30/01/2012 08:45:34 |
Nov 11: Full responsibility for worldwide commercialisation & development of exenatide has transferred to Amylin, after it terminated its alliance with Eli Lilly in order to prevent Lilly from proceeding with its plans to use the same sales force to sell exenatide & linagliptin [30].
17/11/2011 15:53:59 |
Aug 11: Resubmitted to US FDA, which has categorised it as a Class II resubmission requiring up to six months for review and assigned a new Prescription Drug User Fee Act (PDUFA) action date of 28 January 2012. [28]
11/08/2011 16:34:11 |
Jul 11: Launched in the UK [27].
04/08/2011 13:47:35 |
Jul 11: Company planning to resubmit in US by end of 1st week in Aug 11 [26].
28/07/2011 22:04:37 |
Amylin has until end of 2011 to address FDA concerns [23].
22/06/2011 09:53:23 |
Jun 11: Approved in the EU [23].
22/06/2011 09:52:30 |
Apr 11: Positive opinion granted in EU[22].
18/04/2011 08:58:29 |
Oct 10: US negative opinion for once-weekly exenatide. The FDA has issued a complete response letter stating that further information is required, particularly on the potential arrhythmia liability with higher than typical therapeutic levels seen with once-weekly exenatide [18].
21/10/2010 09:27:37 |
Filed in EU Q1 2010 (16).
28/05/2010 14:16:32 |
May 10: FDA decision expected by 22 Oct 10 [15].
23/05/2010 21:42:58 |
April 10: New Drug Application resubmitted
in response to the US FDA complete response letter, for exenatide for extended-release injectable suspension in the treatment of type II diabetes. (14)
26/04/2010 12:48:13 |
Mar 10: The FDA has issued a response letter but is not requesting new pre-clinical or clinical trials. The FDA’s primary concerns relate to product labeling with accompanying risk evaluation and mitigation strategy and clarification of existing manufacturing processes [12].
15/03/2010 21:41:46 |
Dec 09: US decision expected by the end of Q1 2010. An EU submission is expected by the end of the Q2 2010 [10].
12/12/2009 19:01:31 |
Jul 09: new drug application for once weekly admin accepted for review by US FDA (8)
09/07/2009 08:38:52 |
May 09: Application to US FDA submitted (7)
05/05/2009 16:17:08 |
Plans to file in US mid-09 (1)
25/03/2009 10:36:50 |
| |
| Trial or other data |
Nov 12: DURATION-6 published in The Lancet [36].
08/11/2012 10:18:42 |
Feb 12: NICE TA248 published recommonding use of exenatide [35].
22/02/2012 17:49:55 |
Jan 12: In its final draft guidance, NICE confirms its initial draft recommendation supporting use of exenatide. Final guidance is expected in Feb 12 [32].
16/01/2012 08:46:32 |
Dec 11: DURATION-4 published early online in Diabetes Care (30 Dec) [31].
06/01/2012 09:03:30 |
Oct 11: In its preliminary guidance, NICE recommends exenatide prolonged-release suspension for injection (Bydureon) in triple therapy regimens (with metformin & a sulphonylurea, or metformin & a thiazolidinedione) as a treatment option for people with T2DM, when control of blood glucose remains or becomes inadequate (HbA1c of 7.5% or above, or other higher level agreed with the individual), & the person has a body mass index (BMI) of 35 kg/m2 or higher in those of European family origin (with appropriate adjustment for other ethnic groups) & specific psychological or medical problems associated with high body weight, or a BMI below 35 kg/m2, & therapy with insulin would have significant occupational implications or weight loss would benefit other significant obesity-related comorbidities [29].
19/10/2011 09:51:44 |
Jul 11: Results from a randomized double-blind thorough QT (tQT) study assessing the potential of exenatide to increase the QT interval across a wide range of plasma concentrations, which was conducted to satisfy a requirement by the FDA, have been reported. The study, in 75 healthy volunteers, met the pre-specified primary endpoint, demonstrating that exenatide at and above therapeutic levels did not prolong the corrected QT (QTc) interval and found no relationship between QTc interval and plasma exenatide concentrations. The company plans to submit results of the study to the FDA in the 3Q 2011 as part of their reply to the complete response letter [25].
10/07/2011 17:25:47 |
June 11: Analysis from DURATION-1 study that showed the exenatide once-weekly was not associated with clinically relevant QT prolongation in patients with type II diabetes. The change in QTcF from baseline was small and clinically insignificant at 14 weeks (1.7 milliseconds) and 30 weeks (3.0 milliseconds). There was no correlation between change in QTcF and exenatide blood plasma concentrations or renal status. [24]
28/06/2011 08:34:32 |
Mar 11: Top-line results reported from DURATION-6, an open-label 26-week, multicentre study comparing weekly exenatide (2mg) to daily liraglutide (1.8mg) in approx 900 patients with T2DM. Reduction in HbA1c from baseline was 1.3% vs 1.5%, respectively, with exenatide failing to meet the pre-specified primary endpoint of non-inferiority. >85% percent of patients in both treatment arms completed the study. GI adverse events occurred more frequently among liraglutide patients (nausea 20% vs 9%, vomiting 11% vs 4% and diarrhoea 13% vs 6%). Injection site nodule occurred more frequently among exenatide users (10% vs 1%) percent). There were no major hypoglycaemia events in either group [21].
03/03/2011 21:32:24 |
Nov 10: The EXSCEL (EXenatide Study of Cardiovascular Event Lowering) study is designed to determine if there are favorable cardiovascular effects of exenatide extended-release vs standard of care with traditional diabetes medications. The study is underway and will include approximately 9,500 patients, with results expected as early as 2016 [19].
18/11/2010 09:19:17 |
Jun 10: DURATION -3 results published in the Lancet (2010;375:2234-43). In the 26-week, open-label, study 456 patients were randomly allocated to 2mg once weekly exenatide or insulin glargine to target glucose range 4-5.5mmmol/L, plus existing oral treatments, metformin or metformin + sulphonylurea. Change in HbA1c was greater in patients taking exenatide (−1·5%, SE 0·05) vs those taking insulin glargine (−1·3%, 0·06; treatment difference −0·16%, 0·07, 95% CI −0·29 to −0·03). 5% vs 1% of patients respectively, discontinued participation because of AEs (p=0·012). Exanatide resulted in weight loss rather then weight gain. A planned extension period (up to 2·5 years´ duration) is in progress.
28/06/2010 20:03:23 |
Jun 10: Top-line results from DURATION-4 reported. The 26-week study compared BYDUREON monotherapy to sitagliptin, pioglitazone or metformin in 820 patients with T2DM. Study participants were not not on any diabetes therapy when they entered the study. Patients randomized to BYDUREON experienced a reduction in A1C of 1.5% vs 1.2%, 1.6% and 1.5% for the oral hypoglycaemics, respectively. All groups, except the sitagliptin group, achieved an average A1C of <7% by study end. Average weight changes in the four groups were -4.5, -1.7, +3.3 and -4.4lb, respectively. >80% of patients in all treatment arms completed the study. There were no major hypoglycaemia events in any treatment group. The most frequently reported adverse events among BYDUREON users were nausea (withdrawal rate <1%) and diarrhoea [17].
16/06/2010 16:26:19 |
Apr 10: The FDA has raised concerns that Bydureon may be linked to increased cancer risk; data on IV dosing and the once-weekly formulation “seem to give a similar signal” as cancers seen in rodent studies of liraglutide. A statistically significant increase in thyroid cancers was seen in female rats given doses 25 times normal human doses. During the review of liraglutide (which was delayed by 10 months) the FDA said thyroid tumours may be common with all extended-release GLP-1 analogs [13].
13/04/2010 09:12:42 |
Dec 09: positive results reported from a head-to-head study (DURATION-5) of exenatide once weekly vs exenatide twice daily, in 250 patients with type 2 diabetes not adequately controlled on other agents. After 24 weeks of treatment, patients had an HbA1C reduction from baseline of 1.6% vs 0.9% respectively and achieved a mean A1C of 7.1% vs 7.7%. Both treatment groups achieved statistically significant weight loss by the end of the study, with an average loss of 5.1 vs 3lbs respectively. Around 80% of patients completed the study. The most frequently reported AE in both groups was nausea (14% with weekly vs 35% with twice daily injections) [11].
16/12/2009 15:25:47 |
Jul 09: Company announced results from DURATION-3, a 26 week study in 467 patients with type 2 diabetes which compared once-weekly exenatide to Lantus. Patients had previously failed on metformin alone or in combination with sulfonylureas. Patients on exenatide achieved a mean A1C of 6.8% vs 7.0% in those on Lantus. Exentaide was associated with a lower incidence of hypoglycaemia and a mean weight loss of 5.8lb (2.6 kg) after 6 months vs with a weight gain of 3.1 lb (1.4 kg) with Lantus [10].
22/07/2009 21:36:33 |
Jun 09: Two-year efficacy data from the DURATION-1 trial were presented at the ADA-2009 meeting. Reductions in A1C of 1.7% and FPG of 40mg/dL were maintained after two years of treatment. 65% of patients achieved an A1C of ≤7%. Body weight was reduced, patients losing an average of 5.8lbs. Serum lipid profiles were improved, and there was a reduction in systolic blood pressure [8].
20/06/2009 22:53:20 |
Apr 09: Amylin and Lilly are to develop a pen device with a dual chamber cartridge configuration for exenatide once weekly. It will enable patients to mix and administer the preparation from a pre-filled pen device, instead of the syringe and vial currently used in trials (6).
04/05/2009 12:27:49 |
Apr 09: Company state that no cases of thyroid cancer have been documented in clinical trials of Byetta or long-acting Byetta, following the revelation of such a link with liraglutide in animal studies at a recent FDA advisory panel meeting. Nine cases of ´spontaneous´ thyroid cancer have been reported in the approximate 1 million patients taking Byetta, according to FDA records, but none of these tumours were fatal nor of the type under FDA scrutiny with liraglutide (5)
09/04/2009 19:50:56 |
Apr 09: positive results reported from DURATION-2 – a 26-week study vs maximum doses of sitagliptin (100mg/d) or pioglitazone (45mg/d) in 491 patients on metformin. Patients on exenatide once weekly had a reduction in HbA1C of 1.7% vs 1% for sitagliptin and 1.4% for pioglitazone (statistically signif in favour of exenatide). At the end of the study patients on exenatide weighed an average of 14lbs less than patients on pioglitazone and 4lbs less than patients on sitagliptin. (4)
04/04/2009 20:07:33 |
Mar 09: A company meta-analysis of primary cardiovascular events (cardiovascular mortality, myocardial infarction, stroke, hospitalization for acute coronary syndrome and revascularization procedures) across controlled clinical studies of three months or greater, from the exenatide database, showed no increased cardiovascular risk. The relative risk of cardiovascular events in exenatide-treated patients vs. controls, was 0.70 [95%CI 0.38 - 1.31]. This finding will be used to support the cardiovascular safety of exenatide once weekly. (2)
26/03/2009 19:52:05 |
Results from DURATION-1, an open label study in 295 patients aged ≥16 years with type 2 diabetes mellitus, indicte that a new once-weekly formulation (2mg) of exenatide is non-inferior to twice daily formulation in improving glycaemic control. At 30 weeks, the mean reduction in HbA1c was -1.9% (SE 0.1%) in the once-weekly group compared to -1.5% (0.1%) in the twice daily group (mean difference -0.33; 95% CI −0.54% to −0.12%; p=0.0023). More patients receiving once-weekly exenatide achieved an HbA1c of 7% or less (77% vs 61% respectively, p=0.0039). Bodyweight decreased to similar extent in both groups over the trial period. Study published in the Lancet (3)
26/03/2009 19:45:56 |
Mar 09: DURATION-5, a new phase 3b study is starting in which patients with type 2 diabetes will use exenatide once weekly commercial-scale drug product in its final commercial configuration. This randomized, 26-week, open-label study in approximately 240 patients is designed to show superiority of exenatide once weekly compared to BYETTA, support regulatory submissions outside the US and provide additional controlled clinical data on the commercially manufactured product (2).
26/03/2009 19:42:17 |
The DURATION trial programme is designed to demonstrate superiority of exenatide once weekly over other medications, comprises 4 separate trials with results from DURATION 1-3 due in 2009 (1)
25/03/2009 10:39:26 |
| |
| Evidence Based Evaluations |
| NICE |
http://www.nice.org.uk/nicemedia/live/13670/58205/58205.pdf |
| SMC |
http://www.scottishmedicines.org/files/advice/exenatide_Bydureon_FINAL_December_2011_for_website.pdf |
| NYDTC |
http://www.nyrdtc.nhs.uk/docs/nde/NDE_112_Exenatide.pdf |
| MTRAC |
http://www.keele.ac.uk/media/keeleuniversity/fachealth/fachealthsop/mtrac/documents/summary/Exenatide%20weekly%20SUM.pdf |
| NICE |
http://www.nice.org.uk/newsroom/pressreleases/LongActingExenatideForType2Diabetes.jsp |
| NPC |
http://www.npc.nhs.uk/rapidreview/?p=4360 |
| Other |
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002020/human_med_001457.jsp&mid=WC0b01ac058001d124&murl=menus/medicines/medicines.jsp |
| LNDG |
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/Exenatide-once-weekly-Bydureon/ |
| NPC |
http://www.npc.nhs.uk/rapidreview/?p=207 |
| NPC |
http://www.npc.nhs.uk/rapidreview/?p=2077 |
| NPC |
http://www.npc.nhs.uk/rapidreview/?p=2085 |
| NPC |
http://www.npc.nhs.uk/rapidreview/?p=2090 |
| NPC |
http://www.npc.nhs.uk/rapidreview/?p=2792 |
| NHSC |
http://www.pcpoh.bham.ac.uk/publichealth/horizon/outputs/documents/2008/sept-dec/Exenatide.pdf |
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| References |
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| Available only to registered users |
Uk Medicines Information 