PR57069

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

PARIS, June 15/PRN=KYODO JBN/--

    Sanofi (EURONEXT: SAN and NYSE: SNY) 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 (NASDAQ OMX Copenhagen:

ZEAL), 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 (EURONEXT: SAN) and in

New York (NYSE: SNY).

    Forward Looking Statements

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Sanofi's management believes that the expectations reflected in such

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forward-looking information and statements are subject to various risks and

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forward-looking information and statements. These risks and uncertainties

include among other things, the uncertainties inherent in research and

development, future clinical data and analysis, including post marketing,

decisions by regulatory authorities, such as the FDA or the EMA, regarding

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commercial success of therapeutic alternatives, the Group's ability to benefit

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interest rates, the impact of cost containment policies and subsequent changes

thereto, the average number of shares outstanding as well as those discussed or

identified in the public filings with the SEC and the AMF made by Sanofi,

including those listed under "Risk Factors" and "Cautionary Statement Regarding

Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year

ended December 31, 2013. Other than as required by applicable law, Sanofi does

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information or statements.

    SOURCE: Sanofi Diabetes