Sanofi's Lyxumia® (lixisenatide) Showed More Pronounced After-Test-Meal Blood Sugar Lowering Than Liraglutide When Both Were Added to Insulin Glargine

Paris (ots/PRNewswire) -

Sanofi announced today that Lyxumia(R) (lixisenatide) met the
primary endpoint in an 8-week head-to-head pharmacodynamic study
versus liraglutide, showing a significantly more pronounced
post-prandial (after-meal) glucose (blood sugar) lowering effect
after a test-meal than liraglutide when both were added to optimally
titrated Lantus(R) (insulin glargine). Lowering of post-prandial
glucose was measured as change from baseline in incremental area
under the glucose curve for 4 hours after a standardized solid
breakfast, at week 8.

Findings also showed that while both lixisenatide and liraglutide
lowered blood glucose (HbA1c) when added to optimally titrated
insulin glargine, lixisenatide treatment resulted in fewer reports of
gastrointestinal adverse events, a lower mean increase in heart rate
and smaller increases from baseline to week 8 in pancreatic enzyme
(amylase and lipase) levels. The most commonly reported adverse
events in the study were symptomatic hypoglycemia and nausea.
Symptomatic hypoglycemia was more frequent in the lixisenatide group
compared to the liraglutide group. (Full results are available in the
Results of Analysis section.) Lixisenatide is currently approved in
Europe and an investigational drug in the United States, where it is
not approved.

"In this Phase II head-to-head study we saw a significant
difference in the post-prandial glucose lowering effects of
lixisenatide and liraglutide, two GLP-1 receptor agonists, with
similar overall blood sugar reductions," said Riccardo Perfetti,
Senior Medical Officer, Vice President Global Medical Affairs,
Diabetes Division, Sanofi. "The results showed that both medicines
reduced blood glucose, but we found that lixisenatide did this with a
greater delay in gastric emptying, and its use was associated with
differences in safety and tolerability compared to liraglutide. These
differences are interesting and could be further explored to
determine whether differences in gastric emptying benefit patients by
lowering the post-prandial glucose excursion and whether gastric
emptying corresponds to differences in safety and tolerability."

These results were presented at the 74th Scientific Sessions of
the American Diabetes Association, San Francisco, CA. The abstract is
titled: Effect of Lixisenatide vs Liraglutide on Glycemic Control,
Gastric Emptying, and Safety Parameters in Optimized Insulin Glargine
T2DM plus or minus Metformin. (Meier et al. Poster presentation
#1017-P, June 14, 2014).

Results of Analysis

This 8-week, randomized, open-label, three-arm parallel trial,
comparing lixisenatide 20microg with liraglutide 1.2mg and 1.8mg QD
in 142 patients with type 2 diabetes on optimally titrated (SMPG of
80-100mg/dL) insulin glargine treatment with or without metformin,
met its primary endpoint. Results showed a greater reduction in
post-prandial glucose (PPG) from baseline with lixisenatide
(-240.2h.mg/dL, SE 20.0) than with liraglutide 1.2mg (-131.8h.mg/dL,
SE 20.2) and 1.8mg (-157.1h.mg/dL, SE 21.0) for 4 hours after a
standardized solid breakfast (p<0.0001).

At week 8, HbA1c decreased significantly from baseline (p<0.05)
for all groups, and final HbA1c levels were similar in all treatment
arms (6.2 plus or minus 0.4 for lixisenatide, 6.1 plus or minus 0.3
for liraglutide 1.2mg, and 6.1 plus or minus 0.3 for liraglutide
1.8mg). Body weight decreased significantly in all groups (-1.61 plus
or minus 0.47kg, p<0.05 for lixisenatide, -1.78 plus or minus 0.48kg,
p<0.05 for liraglutide 1.2mg, and -2.42 plus or minus 0.49kg,
p<0.0001 for liraglutide 1.8mg).

Symptomatic hypoglycemia was slightly more frequent with
lixisenatide (14 events with lixisenatide versus 9 and 10 events with
liraglutide 1.2mg and 1.8mg, respectively). There was one case of
severe symptomatic hypoglycemia in the lixisenatide arm and one case
of mild asymptomatic confirmed pancreatitis in the liraglutide 1.8mg
arm.

In addition, lixisenatide significantly delayed gastric emptying
more than liraglutide 1.2mg and 1.8mg (LS mean change plus or minus
SE for gastric emptying lag time: 175.6 plus or minus 23.7
[lixisenatide, p<0.0001 for change from baseline] vs. 70.1 plus or
minus 23.8 [liraglutide 1.2 mg, p<0.05 for change from baseline] and
48.9 plus or minus 24.6 [liraglutide 1.8 mg p<0.05 for change from
baseline]; LS mean change plus or minus SE for gastric emptying half
time: 453.6 plus or minus 58.2 [lixisenatide, p<0.0001 for change
from baseline] vs. 175.3 plus or minus 58.5 [liraglutide 1.2 mg,
p<0.05 for change from baseline] and 130.5 plus or minus 60.3
[liraglutide 1.8 mg p<0.05 for change from baseline]). There were
more gastrointestinal adverse events (GI AEs) reported with
liraglutide than with lixisenatide (21 and 22 with liraglutide 1.2mg
and 1.8mg, respectively, versus 17 with lixisenatide) with nausea
reported in 8 and 11 with liraglutide 1.2mg and 1.8mg respectively,
versus 9 with lixisenatide. Liraglutide treatment also resulted in
greater increases from baseline to week 8 in the levels of the
pancreatic enzymes amylase and lipase compared with lixisenatide
(amylase: +8.01IU/L, SE 4.00 and +5.68IU/L, SE 4.13 for liraglutide
1.2mg and 1.8mg, respectively, versus +2.98IU/L, SE 4.00 for
lixisenatide; lipase: +21.12IU/L, SE 7.16 and +20.76IU/L, SE 7.38,
versus +6.97IU/L, SE 7.11). Mean ambulatory monitored 24-hour
increase in heart rate was greater with liraglutide 1.2mg and 1.8mg
than with lixisenatide (9bpm for liraglutide, 3bpm for lixisenatide,
p<0.0001), with no significant differences in 24-hour blood pressure.

About Lixisenatide

In Europe, Lyxumia(R) (lixisenatide) is approved as a once-daily
prandial glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the
treatment of patients with type 2 diabetes mellitus. It remains under
investigation in the U.S. GLP-1 is a naturally-occurring peptide
hormone that is released within minutes after eating a meal. It is
known to suppress glucagon secretion from pancreatic alpha cells and
stimulate glucose-dependent insulin secretion by pancreatic beta
cells.

Lyxumia was in-licensed from Zealand Pharma A/S ,
http://www.zealandpharma.com, and was approved in Europe in 2013 for
the treatment of adults with type 2 diabetes mellitus to achieve
glycemic control in combination with oral glucose-lowering medicinal
products and/or basal insulin when these, together with diet and
exercise, do not provide adequate glycemic control. Lyxumia is
currently approved in over 40 countries worldwide for the treatment
of adults with type 2 diabetes, with commercial launches in Europe,
Japan, Mexico and other markets. Sanofi plans to resubmit the New
Drug Application for lixisenatide in the United States in 2015, after
completion of the ELIXA cardiovascular outcomes study. Lyxumia is the
proprietary name approved by the European Medicines Agency and other
health authorities for the GLP-1 RA lixisenatide.

The Lyxumia pen is the winner of a number of innovative design
awards, including the Good Design Award 2012 and the iF Product
Design Award. The variant of the Lyxumia pen used in Japan won the
Good Design Award (G Mark) 2013.

About Sanofi Diabetes

Sanofi strives to help people manage the complex challenge of
diabetes by delivering innovative, integrated and personalized
solutions. Driven by valuable insights that come from listening to
and engaging with people living with diabetes, the Company is forming
partnerships to offer diagnostics, therapies, services, and devices
including blood glucose monitoring systems. Sanofi markets both
injectable and oral medications for people with type 1 or type 2
diabetes.

About Sanofi

Sanofi, a global healthcare leader, discovers, develops and
distributes therapeutic solutions focused on patients' needs. Sanofi
has core strengths in the field of healthcare with seven growth
platforms: diabetes solutions, human vaccines, innovative drugs,
consumer healthcare, emerging markets, animal health and the new
Genzyme. Sanofi is listed in Paris and in New York .

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ots Originaltext: Sanofi Diabetes
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Contact:
Contacts: Media Relations: Jack Cox, Tel.: +33-(0)1-53-77-46-46,
jack.cox@sanofi.com. Investor Relations: Sébastien Martel, Tel.:
+33-(0)1-53-77-45-45, ir@sanofi.com. Global Diabetes Communications:
Phil
McNamara, Tel.: +1-908-981-5497, Mobile: +1-908-210-4047,
philip.mcnamara@sanofi.com. U.S. Diabetes Communications: Susan
Brooks,
Tel.: +1-908-981-6566, Mobile: +1-201-572-49-94,
susan.brooks@sanofi.com.