Download - 2012/06 - IR - Diabetes
IR Thematic Conference Call on Diabetes
June 12th, 2012
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Forward Looking Statements
This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of
1995, as amended. Forward-looking statements are statements that are not historical facts. These statements
include projections and estimates and their underlying assumptions, statements regarding plans, objectives,
intentions and expectations with respect to future financial results, events, operations, services, product
development and potential, and statements regarding future performance. Forward-looking statements are
generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar
expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking
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to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi,
that could cause actual results and developments to differ materially from those expressed in, or implied or
projected by, the 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 whether and when to
approve any drug, device or biological application that may be filed for any such product candidates as well as
their decisions regarding labelling and other matters that could affect the availability or commercial potential of
such product candidates, the absence of guarantee that the product candidates if approved will be commercially
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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, 2011. Other than as required by applicable law, Sanofi
does not undertake any obligation to update or revise any forward-looking information or statements.
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Agenda
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ORIGIN – A Landmark Study
● Matthew C. Riddle, Professor of Medicine - Oregon Health & Science University
ORIGIN Steering Committee Member
Retrospective Cohort Studies on Insulin and Cancer Risk
● Peter Boyle, DSc FRCP FRCPS FMedSci - International Prevention Research Institute, Lyon
Principal Investigator, Northern European Database Study
Lyxumia® (lixisenatide) – An Ideal Profile in Combination with Basal Insulin
● Riccardo Perfetti, MD - Vice President Global Medical Affairs, Sanofi Diabetes
Sanofi – A Long-term Commitment to Fighting Diabetes
● Pierre Chancel - Senior Vice President, Sanofi Diabetes
Q&A Session
ORIGIN – A Landmark Study
Matthew C. Riddle, Professor of Medicine
Oregon Health & Science University
ORIGIN Steering Committee Member
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Summary of Findings
Compared to standard glycemic care of people
with early diabetes, IGT and/or IFG … using once
daily basal insulin glargine to target a FPG < 95
mg/dl (5.3 mmol/l) for a median of 6.2 years ...
• Maintains near-normal glycemic control
• Has a neutral effect on CV outcomes and on cancers
• Slows progression of dysglycemia
• Modestly increases hypoglycemia
• Modestly increases weight
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Baseline Glycemia (N=12,537)
N %
Prior Diabetes (for ~ 5.4 y) 10321 82
New Diabetes 760 6
IFG and/or IGT 1452 12
No G Drug 5052 40
Metformin 3435 27
Sulfonylurea 3711 30
Other G Drug 351 3
Median FPG 125 mg/dl 6.9 mM
Median A1C 6.4% 6
Glycemic Levels Over 7 Years: A1c
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Summary of Findings
• 1st CV Composite: HR = 1.02 (0.94, 1.11)
• 2nd CV Composite: HR = 1.04 (0.97, 1.11)
• Microvascular Composite: HR = 0.97 (0.90, 1.05)
• Death: HR = 0.98 (0.90, 1.08)
• Cancer: HR = 1.00 (0.88, 1.13)
• Conversion IFG/IGT to DM: HR = 0.72 (0.58, 0.91) P=0.006
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Implications of Findings
• Supplementing endogenous insulin with basal insulin
injections slows progression of dysglycemia
• Although later benefits or harms cannot be ruled out
exogenous basal insulin’s main effect over 6-7 years
is to flexibly lower glucose
• Despite lower glucose levels, routine early use of basal
insulin glargine is not better than guideline-based
standard care in limiting serious health outcomes
• Basal insulin glargine is now the best-studied glucose-
lowering drug available and no new safety concerns
limit early use when needed
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Retrospective Cohort Studies
on Insulin and Cancer Risk
Peter Boyle, DSc FRCP FRCPS FMedSci
International Prevention Research Institute, Lyon
Principal Investigator, Northern European
Database Study
10 © iPRI – International Prevention Research Institute www.i-pri.org
Northern European Database Study of Insulin and
Cancer Risk
A total of 17,800 cancers of all forms, excluding non-melanoma skin cancer, were detected in 447,821 users of insulin since glargine was introduced into the individual countries
The study generated over 1.5 million person-years of exposure to insulin. There was an average of 3.1 years of follow-up for patients using glargine
While the study size, and hence the statistical power and the quality of the individual registries are impressive, this study shares important limitations in common with other studies of this type
Notable among these is the lack of information as to why specific treatments were prescribed for individual patients and why treatments were changed
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© iPRI – International Prevention Research Institute www.i-pri.org
Three Primary Hypotheses were identified by the
CHMP: to compare the risk of
(1) breast cancer in women
(2) prostate cancer in men
(3) colorectal cancer in men and women, who
were prescribed insulin glargine versus those
prescribed human insulin and in all users of
insulin combined
This study found no evidence of an increased risk
of any of these forms of cancer in all users of
insulin glargine or among users of human insulin
Northern European Study: Summary and
Conclusions – Glargine and Cancer Risk
12 © iPRI – International Prevention Research Institute www.i-pri.org
Secondary objectives focused on comparing the
risk of all forms of cancer combined (excluding
non-melanoma skin cancer but including
haematological malignancies) in adults
prescribed insulin glargine versus those
prescribed human insulin and in all users of
insulin combined
There was no evidence of an increased risk of
cancer of all forms found in this study when
users of insulin glargine were compared to other
insulins
Northern European Study: Summary and
Conclusions – Glargine and Cancer Risk
13 © iPRI – International Prevention Research Institute www.i-pri.org
A number of Exploratory Objectives included
comparing the risk of lung cancer and pancreatic
cancer between adults prescribed insulin glargine
and other insulins
The study found no indication of a risk increase of
these forms of cancer with use of glargine
In addition,
no difference was found between the effects of insulin glargine
on cancer risk and those of other long-acting insulins
no effect of metformin associated with the risk of the forms of
cancer considered in this study
no effect of adjusting for confounders including Body Mass
Index (BMI) and tobacco smoking
Northern European Study: Summary and
Conclusions – Glargine and Cancer Risk
14 © iPRI – International Prevention Research Institute www.i-pri.org
Summary and Conclusions
The Northern European Study of Insulin and
Cancer is the largest study of its type and was
based on methodology correcting for flaws
seen in previous studies
There has been no causal association
demonstrated between glargine use and
increased cancer risk in the Northern European
Database Study of Insulin and Cancer
© iPRI – International Prevention Research Institute www.i-pri.org
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Studies of Glargine and Malignancy
21 Independent Estimates
1 million patients with diabetes
3 million person-years of observation
16 © iPRI – International Prevention Research Institute www.i-pri.org
Glargine and Cancer Risk
Previous
Meta-analysis
Northern
European
Update
Meta-analysis
All Cancers 0.88 (0.79, 0.97) 0.98 (0.94, 1.03) 0.91 (0.84, 0.99)
Breast 1.16 (0.97, 1.39) 1.12 (0.99, 1.27) 1.11 (1.00, 1.24)
Breast-new user 0.87 (0.27, 2.80) 1.29 (1.01, 1.63) 1.22 (1.00, 1.48)
Colorectal 0.73 (0.59, 0.91) 0.86 (0.76, 0.98) 0.83 (0.74, 0.94)
Prostate 1.22 (0.99, 1.50) 1.11 (1.00, 1.24) 1.14 (0.93, 1.39)
Lung 0.97 (0.85, 1.11) 0.97 (0.85, 1.11)
Pancreas 0.99 (0.82, 1.20) 0.99 (0.82, 1.20)
17 © iPRI – International Prevention Research Institute www.i-pri.org
Summary and Conclusions
Based on findings from 21 independent
studies involving one million patients and 3
million person-years of exposure, it has not
been possible to identify any increased risk
in any form of cancer among glargine users
compared to those patients who use other
insulins
18 © iPRI – International Prevention Research Institute www.i-pri.org
Lyxumia® (lixisenatide)
An Ideal Profile in Combination
with Basal Insulin
Riccardo Perfetti, MD
Vice President Global Medical Affairs, Sanofi Diabetes
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A GLP-1 Agonist for A1c Control with a Unique Biological Profile
Lyxumia® is the intended trademark for lixisenatide. Lixisenatide is currently not approved or licensed anywhere in the world.
Lixisenatide was in-licensed from Zealand Pharma A/S.
(1) Except for the device intended for Japan (2 steps to maintenance dose with one pen) 20
Pronounced effect on postprandial glucose (PPG) levels
Favorable safety profile with low risk of hypoglycemic events
Once-daily injection, simple 1 step to maintenance dose, 1 pen per dose(1)
A Unique Profile:
®
Fasting and Prandial Glycemia Contribute to A1c
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Time of day
Glu
co
se
(m
mo
l/L
)
22.2
16.6
11.1
5.5
0
06:00 06:00 hrs 10:00 14:00 18:00 22:00 02:00
Diabetic
T2
Diabetic
T2
Meals
Jay Skyler, adapted from Polonsky et al, N Engl J Med 1988
T2D
Not Treated
T2D on Basal Excursion of Blood
Glucose Still Not
Fully Covered
Normal Subjects
T2D Patients Treated
with Basal Insulin(1) (worldwide)
On basal insulin On basal insulin
with controlled fasting
glucose control
but A1c >7%
4 million on other
basal insulins(2)
4 million on Lantus®
4 million
T2D – Type 2 Diabetes A1C – HbA1c or Glycated hemoglobin
(1) Adapted from IMS data (2) Includes all types of basal insulins
Clinical Development Designed to Support Use in Combination with Basal Insulin
®
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Mono
Mono Japan Monotherapy
Placebo-controlled
in OAD failure M (metformin)
F1 (metformin)
M Asia (metformin)
S (sulfonylurea)
P (pioglitazone)
X vs. exenatide Active-controlled
L Asia
L Placebo-controlled
on top of
basal insulin Duo 1
Phase III Program
GetGoal-L & -L Asia: Primary Objective of A1c Change Met
with Lixisenatide on top of Basal Insulin +/- Orals
23
-5 0 5 10 15 20 25
8.6
8.4
8.2
8.0
7.8
7.6
7.4
7.2
7.0
- 8
- 6
- 4
- 2
0
Placebo
(n=123))
-1.72
Lixisenatide
(n=235)
-5.54
2-hour PPG
LS
mean c
hange (
mm
ol/L)
Mean A
1c (
%)
Week
(1) Lixisenatide on top of basal insulin (Lantus® 50.1% of pts) +/- metformin
Duration of T2DM at screening Lixisenatide (L) 12.5 years / Placebo (P) 12.4 years
BMI (kg/m2) at baseline L 31.9/ P 32.6 – Lantus® dose at baseline L 54.0U / P 57.6U
MC Riddle, ADA 2012 (abstract 983-P)
Mean A1c (%) by visit
Lixisenatide
(n=304)
Placebo (n=158)
Week
Mean A
1c (
%)
- 8
- 6
- 4
- 2
0
-7.96
Placebo
(n=142))
-0.14
Lixisenatide
(n=131)
2-hour PPG
(2) Lixisenatide on top of basal insulin (Lantus® 60% of pts) +/- sulfonylurea
Duration of T2DM at screening L 13.7 years / P 14.1 years
BMI (kg/m2 ) at baseline L 25.4 / P 25.2 – Lantus® dose at baseline L 24.9U / P 24.1U
Y Seino, et al. Diabetes, Obesity and Metabolism online, May 30, 2012
LS
mean c
hange (
mm
ol/L)
GetGoal-L(1) GetGoal-L Asia(2)
Mean A1c (%) by visit
LS mean difference lixisenatide vs placebo =
-0.36% (95% CI -0.550, -0.174 ; p=0.0002)
P<0.0001 vs
Placebo
-0.38%
-0.74%
+0.11%
-0.77%
LS mean difference lixisenatide vs placebo =
-0.88% (95% CI -1.116, -0,650 ; p<0.0001)
P<0.0001 vs
Placebo
-5 0 5 10 15 20 25
8.4
8.6
8.2
8.0
7.8
7.6
7.4
7.2
7.0
Lixisenatide
(n=146)
Placebo (n=154)
c
GetGoal Duo 1: Significant A1c & PPG Reduction Achieved with
Lixisenatide on top of Lantus® in T2D Uncontrolled with Orals
24
Lantus ®
+ Metfomin (+/- TZDs)
Lantus ® + Metformin (+/- TZDs)
+ Lixisenatide OR Placebo
-1.0
-2.0
-3.0
Placebo
(n=204)
0.08
Lixisenatide
(n=194)
-3.09
0.0
2-hour PPG
LS mean change in 2-hour postprandial plasma
glucose (mmol/L) from baseline to Week 24
LS
mean c
hange (
mm
ol/L)
Mean A
1c (
%)
Week
Mean A1c (%) by visit
p<0.0001 vs
placebo
7.30%
6.96%
Screen
Duration of T2D at screening: Lixisenatide (L) 9,6 years / Placebo (P) 8,7 years – BMI (kg/m2) at baseline: L 32.0 / P 31.7 – Lantus® dose at baseline L 43.4U / P 44.2U
LS mean difference L vs P in body weight (kg) change from baseline to endpoint: -0,89 (95%CI: -1.42 to -0.35 ; p=0.0012)
LS mean difference L vs P in Lantus® dose from baseline to endpoint: -2.24U (95%CI: -4.26 to -0.22 ; p=0.03) J. Rosenstock, ADA 2012 (abstract 62-OR)
(n=221) (n=215)
16 8 Baseline -12 24
8.6
7.4
7.0
6.6
8.2
7.8
Lixisenatide Placebo
- 30
0
30
60
90
3.5 2.5 2.0 1.5 1.0 0.45 0.5 4.5
Postprandial glucose excursion after a standardized breakfast test in patients with type 2 diabetes
inadequately controlled with metformin (n=143) – Adapted from Kapitza C., IDF 2011 (Poster D-0740)
(1) ClinicalTrials.gov identifier: NCT01596504
Optimal Complementary Pharmacological Profile with Basal Insulins
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More Pronounced Effect on Postprandial Glucose
With Lixisenatide vs. Liraglutide
Mean C
hange f
rom
Pre
meal
Pla
sm
a G
lucose (
mg/d
L)
Time after Study Drug Administration GLP-1
Agonist
Meal
Lixisenatide
Liraglutide
Day -1
(full lines)
Day 28
(dotted lines)
®
c Lixisenatide OR liraglutide
on top of Lantus® after a
standardized breakfast
Target randomization: 140 patients
New study ongoing in
patients on basal insulin(1)
Expected EU regulatory decision in Q4 2012(1)
Recent submission in Japan on June 11th, 2012
CV outcomes study ongoing(2)
● 6,000 T2D patients with a recent ACS event
● Event driven completion
● On track to deliver necessary data to support U.S. filing
U.S. submission planned in Q4 2012
Regulatory Submission on Track
(1) Submitted in EU in October 2011 (EMA acknowledged receipt of the MAA filing in November 2011)
(2) ClinicalTrials.gov identifier: NCT01147250 26
®
Next steps
Fix-Flex Device Has Been Developed for Joint
Administration of Lantus® and Lyxumia®
● Convenience of a single injection
per day coupled with possibility
to adjust Lantus® dose
● Entering phases for
industrialization, validation,
usability and manufacturing
● Device expected to be available
mid-2013 for Phase III initiation
+ ®
Lyxumia® is the intended trademark for lixisenatide. Lixisenatide is currently not approved or licensed anywhere in the world. 27
Sanofi – A Long Term Commitment
to Fighting Diabetes
Pierre Chancel
Senior Vice President - Sanofi Diabetes
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Diabetes Remains One of the Largest Opportunities
in the Healthcare Space
Adults with diabetes worldwide(1) 350m
% of patients not achieving glycemic control target values in the U.S. and EU(2) >50%
Patients remaining undiagnosed in BRIC countries(3) ~2/3
Expected size of global diabetes market in 2015(4) $43-48bn
Expected CAGR growth of global diabetes market between 2011 and 2015(4) 4-7%
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(1) G. Danaei, Lancet 2011; 378: 31-40
(2) Adelphi Disease Specific Program (DSP) III and VII (sample of over 10,000 diabetic patient records)
(3) Internal estimates based on multiple sources
(4) The Global Use of Medicines: Outlook through 2015, IMS Institute for Healthcare Informatics, May 2011
Lantus® is the Leading Insulin in the Leading Segment
NovoRapid® Humalog®
Family
NovoMix® Levemir®
Apidra®
(1) Sales reported by originator companies in their FY2011 reports and converted into EURO using USD/EURO of 1,3917 and DKK/EUR of 7,4507
€3.9bn
€1.7bn €1.7bn
€1.1bn €1.0bn
€190m
Basal
Fast Acting
Premix
30
48%+17%
38%+17%
14%+9%
46%+6%
35%+3%
19%-4%
43%+24%
19%+14%
38% +15%
38%+11%
32%+6%
30%-3%
Basal Insulins Constitute the Leading and Fastest
Growing Insulin Segment
Basal
Premix
Short Acting
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2011 Insulin Market Breakdown by Insulin Type (Value) Market Share (%)
Growth vs. prior year (%)
Western Europe: France, Germany, UK, Italy, Spain, Greece, Cyprus, Malta, Belgium, Luxembourg, Portugal, Netherlands, Austria, Switzerland,
Sweden, Ireland, Finland, Norway, Iceland, Denmark
Emerging Markets: World less the U.S. and Canada, Western Europe, Japan, Australia and New Zealand
Others: Japan, Canada, Australia and New Zealand Source: IMS Q_Global 12/2011
U.S. Western
Europe
Emerging
Markets
Japan/Can
Aus/NZ
37%+14%
37%+16%
26%+19%
Sanofi Holds a Strong Position Among Insulin Players
2011 Insulin Market Share by Insulin Player (Value) Market Share (%)
Growth vs. prior year (%)
Novo
Sanofi
46%+1%
33%+7%
15%+5%
6%-8%
47%+16%
25%+22%
19%+14%
9%+28%
56% -1%25%
+24%
19%+3%
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Lilly
Others
Western Europe: France, Germany, UK, Italy, Spain, Greece, Cyprus, Malta, Belgium, Luxembourg, Portugal, Netherlands, Austria, Switzerland,
Sweden, Ireland, Finland, Norway, Iceland, Denmark
Emerging Markets: World less the U.S. and Canada, Western Europe, Japan, Australia and New Zealand
Others: Japan, Canada, Australia and New Zealand Source: IMS Q_Global 12/2011
U.S. Western
Europe
Emerging
Markets
Japan/Can
Aus/NZ
From Lantus® Brand to Lantus®-based Solutions
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● Encouraging launches
in most EU countries
● Q1 2012 sales of €6m
● Launched in the U.S.
in May 2012
/
● Majority of U.S. patients on
Lantus® expected to use
SoloSTAR® by 2015
● Accounted for >50% of U.S. sales in Q1 2012
New Glargine Formulation with Unique Pharmacokinetics
● New glargine formulation: ● Unique flat PK/PD profile
● Lower injection volume
● Phase III trials ongoing in T2D
high-dose insulin users(1)
● Targeting ~1,600 patients
● Second set of studies expected to start in H2 2012
EDITION I
T2D Patients
Basal Bolus
EDITION II
T2D Patients
Basal + OAD
PK/PD – Pharmacokinetic/Pharmacodynamic OAD – Oral anti-diabetic drugs
(1) ClinicalTrials.gov Identifier: NCT1499082 & NCT01499095
New Insulin Glargine Formulation Depot formation after subcutaneous injection
Schematic illustration
Lantus® New Glargine
Formulation
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Sanofi – A Long-term Commitment to Fighting Diabetes
ORIGIN - Lantus®: neutral effect on CV outcomes, delayed progression
from pre-diabetes to type 2 diabetes, targeted long-term glycemic control
achieved, no association between insulin glargine use and increased risk
of any cancer
Large-scale epidemiological studies: safety profile of Lantus® further
reinforced
Lyxumia®: a new tool for A1c control with a unique biological effect
Multiple initiatives to further develop Lantus® family (e.g. new formulation,
GLP-1 combination) and offer patient centric solutions (e.g. pen devices,
BGM systems)
1
2
3
4
35
Q&A Session
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