Replies to post #113883 on Biotech Values

[DewDiligence]

SNY reports positive phase-3 Lixisenatide data from GetGoal-S study:

http://en.sanofi-aventis.com/binaries/20110412_LIXI_GETGOAL_S_EN_tcm28-31652.pdf

Top-line results of the GetGoal-S study showed that people in the lixisenatide group experienced a significant reduction in their HbA1c levels, with a -0.74% difference versus placebo (p<0.0001) at week 24.

Lixisenatide also significantly improved patients’ 2-hour post-prandial glucose (p<0.0001)
and fasting plasma glucose (p<0.0001) levels. In addition, people treated with lixisenatide had a significant decrease in body weight (p<0.0001), versus those receiving placebo.

In this study, Lixisenatide was tested as an addend to a sulfonylurea with or without metformin (http://clinicaltrials.gov/ct2/show/NCT00713830 ).

[DewDiligence]

SNY’s Lyxumia Hits Phase-3 Primary-Endpoint As Lantus Addend

[Lyxumia (a/k/a lixisenatide) is a qD GLP-1 receptor agonist that’s potentially a direct competitor to Victoza and Byetta/Bydureon. Lantus, a form of basal insulin, is SNY’s biggest-selling drug with annual sales of about $5B.

The trial reported here, called GetGoal-L, is the fifth successful phase-3 study of Lyxumia with no failures. GetGoal-L-Asia, a clone of GetGoal-L that also tested Lantus±Lyxumia, reported in Sep 2010 (#msg-54994790); GetGoal-X, which tested Lyxemia vs Byetta, reported in Feb 2011 (#msg-59446260); GetGoal-S, which tested sulfonylurea±Lyxumia, reported in Apr 2011 (#msg-61962983); and GetGoal-Mono, which tested Lyxumia monotherapy vs placebo, reported in Apr 2010 (#msg-49048670).

Full data on GetGoal-L will be reported at an unspecified medical conference. Four additional phase-3 trials of Lyxumia are in progress with results of some expected during 2011.]

http://en.sanofi.com/binaries/20110531_LYXUMIA_en_tcm28-32746.pdf

›Sanofi GetGoal Program on Lyxumia®, as an Add-on to Basal Insulin, Shows Significant Positive Phase III Results

- Reduction in HbA1c without Significant Increase in Hypoglycemia -

Paris, France - May 31, 2011 - Sanofi (EURONEXT: SAN and NYSE: SNY) announced today that new results from a Phase III study showed that the investigational product Lyxumia® (lixisenatide), when used as an add-on therapy to basal insulin (in association with or without metformin), achieved its primary efficacy endpoint of significantly reducing HbA1c versus placebo for patients with type 2 diabetes without significantly increasing their risk of hypoglycemia.

GetGoal-L is one of nine studies in the GetGoal Phase III clinical program, and the second trial to investigate the benefits of lixisenatide 20µg once-daily combined with basal insulin [i.e. Lantus]. It was a randomized (double-blind), placebo-controlled study with a 24-week main treatment period, and a total of 495 patients received either lixisenatide or placebo.

GetGoal-L showed a significant reduction in HbA1c levels (p=0.0002) with lixisenatide, without a significant increase in the incidence of symptomatic hypoglycemia (p=0.14) versus placebo.

In addition, patients treated with lixisenatide had significantly improved postprandial plasma glucose after a test meal (p<0.0001). Patients in the lixisenatide arm of the study also 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. As expected with a GLP-1, the most commonly reported adverse event with lixisenatide was nausea with a low rate of discontinuation.

“These positive efficacy and safety results are another important milestone in the GetGoal clinical trial program and show the potential value of adding Lyxumia® (lixisenatide) to basal insulin to improve glycemic control,” said Pierre Chancel, Senior Vice President, Global Diabetes Division at Sanofi. “The findings from this and previous studies reinforce a continuing positive trend demonstrating the potential of lixisenatide to improve the lives of people with type 2 diabetes.”

The full study results from GetGoal-L are planned to be presented at a medical congress.

About lixisenatide (AVE 0010) Lixisenatide, a glucagon-like peptide-1 agonist (GLP-1), is in development for the treatment of patients with type 2 diabetes mellitus. Lixisenatide was in-licensed from Zealand Pharma A/S (Copenhagen, Denmark), www.zealandpharma.com. Lyxumia® is the intended trademark for lixisenatide. Lixisenatide is not currently approved or licensed anywhere in the world.

GLP-1 is a naturally-occurring peptide that is released within minutes of eating a meal. It is known to suppress glucagon secretion from pancreatic alpha cells and stimulate insulin secretion by pancreatic beta cells. GLP-1 receptor agonists are in development as an add-on treatment for type 2 diabetes, and their use is endorsed by the European Association for the Study of Diabetes, the American Diabetes Association, the American Association of Clinical Endocrinologists and the American College of Endocrinology.

About the GetGoal Phase III Clinical Program

The GetGoal Phase III clinical program will provide data for the efficacy and safety of lixisenatide in adults with type 2 diabetes treated with various oral anti-diabetic agents or insulin. With nine trials in the program, GetGoal started in May 2008 and has enrolled more than 4300 patients. To date GetGoal-X, GetGoal-Mono, GetGoal-L Asia and GetGoal-S have reported positive top-line results supporting efficacy and safety for lixisenatide. Further results are expected during 2011.‹

[DewDiligence]

SNY details Lyxumia-vs-Byetta data from GetGoal-X:

http://finance.yahoo.com/news/Positive-Results-for-prnews-511265329.html?x=0&.v=1

• Lixisenatide once daily achieved its primary endpoint of non-inferiority in A1C reduction versus exenatide twice daily (LS mean +/- SE change from baseline: -0.79 +/- 0.05 vs. -0.96 +/- 0.05).

• Discontinuations due to adverse events (mainly gastrointestinal events including nausea, diarrhea and vomiting) were 33 (10.4%) in the lixisenatide group and 41 (13.0%) in the exenatide group.

• Significantly fewer patients experienced symptomatic hypoglycemia with lixisenatide (2.5% vs. 7.9%, p<0.05), with 6-fold fewer hypoglycemic events (8 vs. 48) versus exenatide.

So far, so good; however, I don’t understand this:

• Mean body weight significantly decreased from baseline in the lixisenatide group compared to the exenatide group (94.5 to 91.7 kg with lixisenatide vs. 96.7 to 92.9 kg with exenatide).

How can that be right?

The success of GetGoal-X on the primary endpoint was reported in Feb 2011 (#msg-59446260), but this weekend was the first time the data were presented.

See the prologue of #msg-63710626 for more info on the Lyxumia phase-3 program.