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New Drugs Online Report for lixisenatide
Generic Name:
Trade Name: Lyxumia 
Synonym: AVE0010, ZP 10 
Entry Type: New molecular entity  
Development and Regulatory status
UK: Launched 
EU: Launched 
US: Pre-registration (Filed) 
UK launch Plans: Available only to registered users
Actual UK launch date: May 2013 
Sep 15: The FDA have agreed to review Sanofi’s application to market once-daily prandial GLP-1 receptor agonist lixisenatide for the treatment of adults with type 2 diabetes. Sanofi had intended to file lixisenatide in the US back in 2013, but pulled back the application on concerns that potential public disclosure of early interim data from the ELIXA trial, even with safeguards, could compromise the integrity of the ongoing study [32].  
01/10/2015 14:38:12
Sep 15: Currently pre-registration in US [31]. 
09/09/2015 13:58:44
Sep 13: Sanofi withdraws its application to market lixisenatide in the US, while waiting to collect all data from the ongoing 6,000-patient ELIXA CV study. They plan to refile in 2015 [30]. 
12/09/2013 12:13:21
May 13: Launched in the UK [27]. 
03/05/2013 10:13:07
Feb 13: Approved in the EU [24]. 
06/02/2013 09:43:36
Jan 13: Filed in the US [22].  
10/01/2013 08:30:06
Nov 12: the EMA has issued a positive opinion recommending the approval of once-daily Lyxumia (lixisenatide) for the treatment of adults with T2DM to achieve glycaemic control in combination with oral glucose-lowering medicinal products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycaemic control [21]. 
17/11/2012 18:47:30
Dec 11: Plan to file in US 4Q 2012 [16]. 
07/12/2011 09:11:20
Nov 11: Sanofi has submitted a marketing authorisation application (MAA) for Lyxumia (lixisenatide) for type II diabetes in Europe. [15]  
04/11/2011 16:56:57
Jul 11: Filing anticipated in EU in Q4 2011 [13]. 
29/07/2011 10:38:31
Apr 10: Filing for approval now planned for 2011 [6]. 
22/04/2010 22:09:22
Filing for approval of immediate-release AVE 0010 expected in 2010 (3). 
02/04/2009 15:40:12
May 08: Worldwide PIII programme initiated to assess efficacy and safety of AVE 0010 inj in combination with other drugs (metformin, sulfonylureas, basal insulin), plus comparison with exenatide (all completion est. mid 2010) & a monotherapy study (completion est. Jul 09) (3). 
02/04/2009 15:39:43
Trial or other data
May 13: GetCoal-X published in Diabetes Care. Lixisenatide once daily was noninferior to exenatide twice daily. The LS mean change in HbA1c was −0.79% (mean decrease 7.97 to 7.17%) for lixisenatide vs −0.96% (mean ± SD 7.96 to 7.01%) for exenatide, and treatment difference was 0.17% (95% CI, 0.033–0.297), meeting a predefined noninferiority upper CI margin of 0.4%. Responder rate (HbA1c <7.0%) and improvements in fasting plasma glucose were comparable. Both agents induced weight loss (from 94.5 to 91.7 kg and from 96.7 to 92.9 kg with lixisenatide and exenatide, respectively). Incidence of adverse events (AEs) was similar for lixisenatide and exenatide, as was incidence of serious AEs (2.8 and 2.2%, respectively). Discontinuations attributable to AEs occurred in 33 lixisenatide (10.4%) and 41 exenatide (13.0%) patients. In the lixisenatide group, fewer participants experienced symptomatic hypoglycemia (2.5 vs. 7.9%; p< 0.05), with fewer gastrointestinal events (especially nausea; 24.5 vs. 35.1%; p< 0.05) [29]. 
24/05/2013 10:32:25
May 13: GetGoal-L published in Diabetes Care [28]. 
08/05/2013 08:25:56
Apr 13: GetGoal-M published in Diabetes Care [26]. 
10/04/2013 08:53:17
Apr 13: GetGoal Duo 1 published in Diabetes Care [25]. 
10/04/2013 08:46:16
Jan 13: NCT01768559 a PIII randomized, open-label, active-controlled, 3-arm parallel-group, 26-week study comparing the efficacy and safety of lixisenatide to that of insulin glulisine once daily and insulin glulisine three times daily in 855 patients with T2DM insufficiently controlled with insulin glargine with or without metformin. Primary endpoints are change in HB1Ac and body weight at week 26. The study starts Jan 13 and is due to complete Aug 14 [23]. 
24/01/2013 17:16:06
Jun 12: Results of the GetGoal-L study reported at the American Diabetes Association congress. The 24-week double-blind RCT in 495 people with T2DM insufficiently controlled on basal insulin +/- metformin, found that lixisenatide reduced mean HbA1c from baseline by -0.74% vs. -0.38% with placebo (p=0.0002) and decreased mean 2-hour post-prandial glucose (-5.54 mmol/L vs. -1.72 mmol/L, p < 0.0001), after a standardized breakfast. Patients on lixisenatide had a mean reduction in body weight of -1.8 kg (vs. -0.52 kg with placebo, p < 0.0001). The incidence of per protocol symptomatic hypoglycemia was 27.7% vs. 21.6%. Severe hypoglycemia occurred in 1.2% vs 0% [20].  
11/06/2012 21:39:30
Jun 12: Results of GetGoal Duo 1 reported at the American Diabetes Association congress. GetGoal Duo 1 is a double-blind RCT of lixisenatide plus insulin glargine and OADs (mostly metformin). During the 12-week run-in phase, 898 insulin-naďve patients were treated with insulin glargine, which was titrated to reach a target fasting plasma glucose (FPG) of 80-100 mg/dL. Subsequently, 446 patients with HbA1c > 7% (despite controlled FPG levels) received either once-daily lixisenatide 20µg or placebo for 24 weeks while metformin and insulin glargine titration were continued. HbA1c decreased from a mean of 8.6% to 7.6% during the run-in period and further decreased with the addition of lixisenatide to a mean value of 7% after 24 weeks vs 7.3% in patients on placebo (p < 0.0001). More patients on lixisenatide achieved target HbA1c < 7.0% (56.3% vs. 38.5%, p=0.0001). Incidence of symptomatic hypoglycemia was 22.4% vs. 13.5% [20]. 
11/06/2012 21:39:15
Mar 12: GetGoal-Mono study (n=361) published early online in Diabetes Care 19 Mar. Once-daily lixisenatide statistically significantly improved HbA1c (mean baseline 8.0%) in both gps (vs. placebo −0.54% for 2-step, −0.66% for 1-step; p<0.0001). More lixisenatide pts achieved HbA1c <7.0% (52.2% 2-step, 46.5% 1-step) & ≤6.5% (31.9% 2-step, 25.4% 1-step) vs. placebo (26.8% & 12.5%, respectively; p<0.01). Mean decreases in body weight (approximately 2 kg) were observed in all gps. The most common adverse events were gastrointestinal - nausea was the most frequent (lixisenatide 23% overall, placebo 4.1%). Symptomatic hypoglycaemia occurred in 1.7% of lixisenatide & 1.6% of placebo pts, with no severe episodes [19]. 
20/03/2012 17:59:43
Feb 12: Top line results from the 24 week PIII GetGoal-P study reported. The study evaluated adding lixisenatide to pioglitazone therapy with or without metformin vs placebo in 484 patients with T2D. Lixisenatide achieved the primary efficacy endpoint, reducing mean HbA1c levels from 8.08% to 7.06% vs 8.05% to 7.59% in the placebo group (p<0.0001). Symptomatic hypoglycemia rates were low in both groups. (3.4% vs 1.2%). The most frequent adverse event was nausea which lead to discontinuation in 1.9% of patients on lixisenatide vs 0% on placebo [18].  
09/02/2012 19:30:47
Dec 11: Results from GetGoal-M PIII study. Study evaluated efficacy and safety of lixisenatide as morning or evening injections in 680 pts with type 2 diabetes insufficiently controlled with metformin. Both am and pm doses gave significant reductions of HbA1c over 24 weeks vs. placebo (p<0.0001) and fasting plasma vs. placebo (p<0.005). Proportion of pts achieving HbA1c <7.0% was 43% (morning dose), 41% (evening dose) and 22% (placebo). Body weight was reduced in all 3 groups. No severe episodes of hypoglycaemia occurred and fewer patients treated with lixisenatide required treatment for hyperglycaemia [17].  
12/12/2011 08:54:33
Dec 11: Results from the PIII 24-week GetGoal Duo 1 RCT reported. Lixisenatide plus insulin glargine achieved the primary study endpoint significantly reducing HbA1c vs insulin treatment alone in patients with T2DM. In the 12-week run-in period, patients were started on insulin glargine and titrated to a target fasting plasma glucose of 80-100 mg/dL. After 12 weeks, 446 patients with HbA1c >7% despite controlled fasting plasma glucose, were randomized to either lixisenatide once-daily or placebo and insulin glargine and metformin were continued. During run-in, patients´ HbA1c decreased on average from 8.6% to 7.6%. In the randomised period, HbA1c decreased further with lixisenatide vs placebo (p<0.0001) after 24 weeks to a mean value of 6.96%. More patients in the lixisenatide arm achieved target HbA1c <7.0% (56.3% vs 38.5%, p=0.0001). Lixisenatide also improved 2-hour post-prandial glucose with a mean difference of -3.16 mmol/L (p<0.0001) vs placebo. The mean difference in body weight change between the lixisenatide and placebo was -0.89 kg (p=0.0012). 22.4% and 13.5% of patients reported symptomatic hypoglycaemic events [16]. 
07/12/2011 09:05:52
Sept 11: Results from GetGoal-F1 24-week trial (n=482). Pts randomised to lixisenatide one-step dose increase (10µg for two weeks, then 20µg); lixisenatide two-step dose increase (10µg for one week, 15µg for one week, then 20µg), or placebo, as add on to metformin. Lixisenatide significantly reduced HbA1c from baseline to week 24 in both treatment regimens, vs. placebo (one-step: -0.92%; two-step: -0.83% vs. placebo: -0.42%; p < 0.0001). HbA1c targets of ≤ 6.5% and HbA1c < 7.0% with the one-step regimen was met in 25.6% and 47.4% of pts and with the two-step regimen was 20.4% and 42.1% of pts versus 7.6% and 24.1% of pts treated with placebo, respectively. Body weight was reduced in both the one- and two-step regimens by -2.63kg (p=0.0042) and -2.68kg respectively (p=0.0025), vs. -1.63kg with placebo. [14]  
13/09/2011 08:58:55
June 11: More results from the GetGoal-X 24-wk trial. HbA1c reduced from baseline by -0.79% (lixisenatide) vs. -0.96% (exenatide). Mean fasting blood glucose improved by -22mg/dL (lixisenatide) vs. -26.2mg/dL (exenatide). HbA1c <7.0% achieved by 48.5% and 49.8% respectively. Mean body weight decreased by 2.8kg (lixisenatide) vs. -3.8kg (exenatide). [12] 
28/06/2011 08:48:15
May 11: Top line results from the PIII GetGoal-L study reported. The study randomized 495 patients to either lixisenatide or placebo as an add on to basal insulin (with or without metformin) and had a 24-week main treatment period. Lixisenatide significant reduced HbA1c levels (p=0.0002) vs placebo without a significant increase in the incidence of symptomatic hypoglycemia (p=0.14). Patients on lixisenatide also had significantly improved postprandial plasma glucose after a test meal (p<0.0001) and reported a significant reduction in body weight (p<0.0001). These results confirm those previously reported on GetGoal-L Asia, this time in a broader population including both Caucasian and Asian patients. The most commonly reported adverse event with lixisenatide was nausea with a low rate of discontinuation [11]. 
15/06/2011 14:16:48
Apr 11: Top line results from the PIII GetGoal-S study report that lixisenatide achieved the primary endpoint, significantly reducing HbA1c (-0.74% difference vs placebo (p<0.0001)) at week 24. It also reduced patients’ 2-hour post-prandial glucose (p<0.0001) and fasting plasma glucose (p<0.0001) levels, and was associated with a decrease in body weight (p<0.0001), The GetGoal-S trial investigated the efficacy and safety of lixisenatide as an add-on therapy for 859 people with T2DM inadequately controlled by sulfonylureas, with or without metformin [10].  
13/04/2011 09:48:30
Feb 11: Top line results from the PIII GetGoal-X study report that lixisenatide achieved its primary endpoint of non-inferiority in HbA1c reduction from baseline, vs exenatide twice-daily. In addition, significantly fewer people on lixisenatide reported hypoglycaemic events: incidence of symptomatic hypoglycaemia was 2.5% vs. 7.9% (p<0.05). GetGoal-X, a randomized, open-label, study, with a 24-week main treatment period enrolled 639 people with T2DM inadequately controlled with metformin [9]. 
03/02/2011 14:12:26
Sept 10: Positive study findings from the first GETGOAL MONO study with lixisenatide were presented on 20 September 2010 at the European Association for the Study of Diabetes (EASD) 46th Annual Meeting in Stockholm, Sweden. The results showed that lixisenatide, when dosed once-daily as a monotherapy, had a significant effect on postprandial blood glucose control and A1C levels with mean decreases in body weight observed in all dose groups. [8] 
01/10/2010 08:31:18
Sept 10: PIII GETGOAL-L-ASIA 24-wk trial results. Lixisenatide when dosed once-daily with insulin significantly improved glycaemic control in pts with type 2 diabetes. The addition of lixisenatide once daily to the basal insulin significantly reduced A1C levels by 0.88% versus placebo (p<0.0001). [8] 
01/10/2010 08:30:44
Apr 10: A PIII programme with the combination of lixisenatide/Lantus (insulin glargine) expected to start in 2010 [5].  
15/04/2010 22:11:06
Apr 10: Results from the first, placebo-controlled study of the GetGoal PIII trial programme reported. The 12-week study involved 361 patients with T2D not currently receiving glucose-lowering therapy and with HbA1c between 7 and 10%. Patients were randomized to one of four once-daily treatment regimens in which the dose was titrated upwards in weekly steps: lixisenatide two-step titration (10mcg, 15mcg then 20mcg), lixisenatide one-step titration (10mcg then 20mcg), placebo two-step titration or placebo one-step titration. Baseline characteristics were similar among groups in terms of mean age (53.7 years), diabetes duration (2.5 years) and HbA1c (8.04%). HbA1c was significantly reduced in both lixisenatide groups vs placebo, and significantly more patients in the lixisenatide groups achieved HbA1c <7% (46.5 to 52.2% vs 26.8%). Lixisenatide also significantly improved fasting plasma glucose and two-hour post-prandial glucose with a pronounced decrease in 2-hour post-prandial glucose excursion. Lixisenatide was generally well tolerated. The most common AE was nausea (20 to 24% vs 4% with placebo). The incidence of symptomatic hypoglycaemia was low (1.7%) and similar in the lixisenatide and placebo groups. Complete study findings submitted for presentation at the European Association for the Study of Diabetes (EASD) in Sep 2010 [5]. 
15/04/2010 22:10:48
Jun 09: A PIII study evaluating the safety and glycaemic control of AVE0010 montherapy in 66 patients with Type 2 Diabetes started in May 09. Expected completion date Mar 11 [4] 
16/06/2009 21:55:53
Evidence Based Evaluations
NICE (MPC)  http://www.nice.org.uk/Advice/ESNM26 
AWMSG  http://www.awmsg.org/awmsgonline/app/appraisalinfo/863 
SMC  http://www.scottishmedicines.org.uk/files/advice/lixisenatide_Lyxumia_FINAL_August_2013_Amended_29.08.13_for_website.pdf 
EPAR  http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002445/human_med_001615.jsp&mid=WC0b01ac058001d124 
NHSC  http://www.hsc.nihr.ac.uk/files/downloads/1285/1790.8d52f92c630279c6c3c59bac3ba413db.pdf 
Available only to registered users
BNF Category:
Antidiabetic drugs (06.01.02)
Pharmacology: exendin-4 analogue  
Epidemiology: In 2011 the UK prevalence of diabetes was 4.45% (about 2.9 million people). It is thought a further 850,000 are undiagnosed. The prevalence is projected to increase to 5 million people by 2025. About 90% of patients with diabetes have type 2 disease.  
Indication: Type 2 diabetes mellitus 
Method(s) of Administration
Company Information
Name: Sanofi  
US Name: Sanofi  
Further Information
Anticipated commissioning route (England)
High cost drug list? Awaiting Update
Tariff Likely in tariff.
Implications Available only to registered users