bristol myerd squibb European Association for the Study of Diabetes (EASD) Highlights

EASD 2008 Highlights
Investor Teleconference
Sept 9, 2008

1
Not For Promotional Use

Comments will be about the Company’s future plans and
prospects that may be forward-looking statements under
the Private Securities Litigation Reform Act of 1995.
We caution that actual results may differ materially from
those indicated by these forward-looking statements as
a result of various important factors, including those
discussed in the Company’s most recent annual report on
Form 10-K, periodic reports on Form 10-Q and current
reports on Form 8-K. These documents are available from
the SEC, the Bristol-Myers Squibb web site or from
Bristol-Myers Squibb Investor Relations. While we may elect
to update forward-looking statements at some point in the
future, we specifically disclaim any obligation to do so,
even if our estimates change.

2

Diabetes: A Growing, Global Problem
Type 2 Diabetes prevalence expected to grow
from 190 million to 330 million by 2030

Europe prevalence is
Diabetes growing rapidly lower (~4.6%), but
in U.S. – current increasing, especially in
prevalence rate 6.7% the southern countries

Mexico – highest India and China will make up
prevalence rates in nearly 50% of the total
the world: 12.4% number of patients with
diabetes in 2030

Source: WHO 3
Not For Promotional Use 3

Majority of Patients Are Not Optimally
Controlled

Percentage of patients not controlled,
100 by market (relative to HbA1c Target of 7.0%)
60% of 80
69
US diabetic 64 62
Patients (%)
patients 58 57
60
51
do not know
their A1c or 40
FPG values
20

0

UK FR GER ITL SPN
US

Source: Adelphi, 2006 Disease Specific
Programmes, NHWS 2006
4

The Progressive Nature of Type 2 Diabetes
Ultimately Overwhelms Medications
Glycemic Control in an Illustrative Patient
Potential =
Slope 5
treatment
p er
0.75%
change
yrs.
First
5yr s
Agent
Goal*
HbA1c

A1c=<7

Goal**
A1c=<6.5

Normal***
A1c=5%
~30 Years
There remains a need for new therapies
Sources: ADOPT, UKPDS
(*) According to the ADA; (**) according to the AACE/ACE;
(***) according to the NIH 5

EASD 2008: Dapagliflozin
Data on dapagliflozin was presented from the largest and longest
(12 weeks) trial of an SGLT2 Renal Glucose Reabsorption Inhibitor
to date. Results demonstrated that dapagliflozin:

Induced controlled glucosuria

Improved glycemic control
– Reduced fasting glucose
– Reduced postprandial glucose
– Reduced HbA1c

Lowered weight
Showed little propensity to cause hypoglycemia
Demonstrated no clear adverse safety or tolerability signals
over 12 weeks

Phase 2 Study, EASD Sept 2008 6

Saxagliptin Overview

Specifically designed to be a selective inhibitor
with extended binding to the DPP-4 enzyme

Completed Phase 3 registrational program

New Drug Application officially filed by the FDA

Marketing Authorization Application accepted for
review by the EMEA

7

Patient Exposures Throughout
Saxagliptin Program
Phase 1 and 2
~110 subjects exposed to saxagliptin at 20-80x the
5 mg dose for up to 6 weeks
~670 subjects exposed to saxagliptin at 2-10x the
5 mg dose for up to 12 weeks

Phase 3
~1000 patients treated at 10 mg dose for up to 2 years
>3000 patients treated at any dose in Phase 3

8

Saxagliptin Profile is Competitive
Produced significant reductions in all key
measures of glucose control in treatment naïve
patients and patients treated with commonly
used oral agents
Generally well tolerated in clinical trials across
all usage situations
– Clinical correlates to the skin lesions in monkeys
have not been identified in human clinical trials
of saxagliptin

Life cycle program underway

9

Saxagliptin Initial Combination with
Metformin Design: EASD 2008
1 Wk PBO 24 Wks N=1306
Lead-in
PBO + MET IR (with titration)*†

Treatment-Naïve T2D
SAXA 10 mg + PBO†

Superiority Test

(HbA1C ≥8%-≤12%)
SAXA 5 mg + MET IR (with titration)*†

Superiority Test

SAXA 10 mg + MET IR (with titration)*†

*MET IR titration: Forced titration from 500 mg to 1000 mg at wk 1, then elective titration at wks 2, 3, 4, and
5 to achieve mean fasting plasma glucose (FPG) <110 mg/dL (maximum MET 2000 mg total daily dose).
†Ifrescue criteria met in short term, add pioglitazone 15-45 mg o.d. and enter long-term phase; pioglitazone
rescue also available in long-term extension.

Phase 3 Study -039, EASD Sept 2008 10

HbA1C Adjusted Mean Changes from
Baseline at Week 24*
Saxagliptin (mg)
Dose 5 + Met 10 + Met 10 Met
n= 306 315 317 313
Baseline mean (%) 9.4 9.5 9.6 9.4
0.0

-0.5

-1.0
Δ HbA1C (%)
with 95% CI -1.5

-1.7
-2.0
-2.0

-2.5
-2.5 †‡
-2.5 †‡
-3.0
*LOCF=last observation carried forward
†P<.0001 vs Saxa 10 mg
‡P<.0001 vs Met


Patients Achieving Therapeutic Glycemic
Response (HbA1C ≤6.5% and <7%) at Week 24*

60

Patients
Achieving 40
Glycemic
Response (%)
with 95% CI
20

45.3† 60.3† 40.6‡ 59.7† 20.3 32.2 29.0 41.1

≤6.5% <7.0% ≤6.5% <7.0% ≤6.5% <7.0%
≤6.5% <7.0%
0
Saxa 5 mg Saxa 10 mg Saxa 10 mg Met
+ Met + Met n = 320 n = 314
n = 307 n = 315
*LOCF
†P<.0001 vs Saxa 10 mg and vs Met
‡P <.0001 vs Saxa 10 mg and P =.0026 vs Met


HbA1C Adjusted Mean Change:
Subgroup Analysis by Baseline HbA1C
Baseline HbA1C <8% ≥8%-<9% ≥9%-<10% ≥10%
0.0

-0.5
Δ HbA1C (%) with 95% CI

-0.5
-1.0
-1.0
-1.0
-1.1 -1.2
-1.5 -1.4
-1.5
-2.0 -1.9
-2.0 -2.0
-2.5
-2.5
-2.5 -2.5
-2.7
-3.0

-3.3 -3.3
-3.5
Saxagliptin + Met

-4.0 5 mg 10 mg Saxa 10 mg Met


FPG Adjusted Mean Changes from
Baseline at Week 24*
Saxagliptin (mg)
Dose 5 + Met 10 + Met 10 Met
n= 315 317 327 320
Baseline mean (mg/dL) 198.9 204.3 200.9 199.1
0

-10

-20

Δ FPG (mg/dL) -30
-31
with 95% CI
-40

-50 -47

-60
-60 †‡
-62 † §
*LOCF
-70
†P<.0001 vs Saxa 10 mg
‡P=.0002 vs Met
§P<.0001 vs Met


Most Common (≥5%) Reported
Adverse Events
Saxa 5 mg Saxa 10 mg Saxa
+ Met + Met 10 mg Met
n=320 n=323 n=335 n=328
Total patients with
177 (55.3) 185 (57.3) 179 (53.4) 192 (58.5)
at least 1 AE, n (%)

Nasopharyngitis 22 (6.9) 8 (2.5) 14 (4.2) 13 (4.0)

Headache 24 (7.5) 32 (9.9) 21 (6.3) 17 (5.2)

Diarrhea 22 (6.9) 31 (9.6) 10 (3.0) 24 (7.3)

Hypertension 15 (4.7) 17 (5.3) 15 (4.5) 11 (3.4)


Conclusions
Saxagliptin, given in combination with metformin as
initial therapy, led to clinically relevant improvements
that were significantly greater than either treatment
alone across all key glycemic parameters studied
including:
– HbA1C
– FPG
– Proportion of patients with HbA1C <7%
– PPG during OGTT

Saxagliptin, given in combination with metformin as
initial therapy, was well tolerated over the course of the
study


Saxagliptin Add-on TZD Study Design:
EASD 2008
2-Wk TZD +
PBO Lead-in 12 Months LTE
24 Wk (N=565)

PBO + TZD* PBO + TZD*
Stable Dose
TZD†‡ ≥12 Wk
Superiority
T2D
SAXA 5 mg o.d. + TZD* SAXA 5 mg o.d. + TZD*

HbA1c ≥7.0%–≤10.5% Superiority

SAXA 2.5 mg o.d. + TZD*
SAXA 2.5 mg o.d. + TZD*

*If rescue criteria met in short-term phase, add metformin 500–2500 mg total daily dose, and enter LTE phase; metformin rescue was
also available in the LTE phase.
†Stabledose of TZD defined as pio 30 or 45 mg total daily dose or rosi 4 or 8 mg total daily dose. TZD dose at entry fixed for
duration of study.
‡If determined to be medically appropriate, a switch from rosi to pio was permitted.

[CSR Fig 3.1]

HbA1C Adjusted Mean Change from Baseline
at Week 24 (LOCF)
Saxagliptin (mg) + TZD
Dose 2.5 5 Pbo + TZD
n= 192 183 180
Baseline Mean 8.25 8.35 8.19

-0.1

-0.3
-0.3

-0.5
Δ HbA1C (%)

Source: CV181013 – Figure 7.2.1A
with 95% CI
-0.7 -0.7

p = .0007
-0.9
-0.9
-1.1
p <.0001

Fasting Plasma Glucose Adjusted Mean
Change from Baseline at Week 24 (LOCF)
n= 193 185 181
163.0 159.5 162.4
Baseline Mean (mg/dL)
5.0

0.0

-2.8
-5.0
Δ FPG (mg/dL)

-10.0
with 95% CI

-15.0 -14.3
-17.3
-20.0
p = .0053
p = .0005
-25.0


Postprandial Glucose AUC Adjusted Mean
n= 151 131 123
48301 47866 47256
Baseline Mean
(mg min/dL)
0

-2000
-2690
-4000
Δ PPG AUC
(mg min/dL) -6000
with 95% CI

CV181013 – Figure 7.3.3
-8000
-7849

-9269
-10000 p <.0001

p <.0001
-12000

Most Common (≥5%) Reported Adverse Events
During 24-Week Treatment
Saxa 2.5 mg Saxa 5 mg All Saxa
Pbo + TZD
+ TZD + TZD + TZD
N = 184
N = 195 N = 186 N = 381
Total subjects with AE 121 (62.1) 138 (74.2) 259 (68.0) 123 (66.8)
Adverse Events (≥ 5%)
Upper respiratory tract
15 (7.7) 17 (9.1) 13 (7.1)
32 (8.4)
infection
Urinary tract infection 7 (3.6) 12 (6.5) 12 (6.5)
19 (5.0)
Arthralgia or joint pain 11 (5.6) 5 (2.7) 16 (4.2) 5 (2.7)
Headache 9 (4.6) 10 (5.4) 19 (5.0) 7 (3.8)
Dizziness 5 (2.6) 6 (3.2) 11 (2.9) 10 (5.4)
Oedema peripheral 6 (3.1) 15 (8.1) 21 (5.5) 8 (4.3)
Hypertension 11 (5.6) 8 (4.3) 19 (5.0) 9 (4.9)


Conclusions
In patients with type 2 diabetes not achieving
glycemic control on TZD monotherapy, the
addition of saxagliptin provided statistically
significant and clinically meaningful
improvements in the key parameters of glycemic
control.
Significantly more patients achieved the HbA1C
target of <7% at week 24 with saxagliptin added to
TZD therapy vs TZD monotherapy.
Over 24 weeks, the combination of saxagliptin
and TZD was generally well tolerated.


Saxagliptin Add-on SU Study Design:
EASD 2008
24 Weeks (N=768) 12 Months LTE
4 Weeks

GLY 7.5 mg +
PBO Lead-in
UP-GLY 10/15/20 mg* o.d. + PBO†
UP-GLY 10/15 mg* o.d. + PBO†
T2D
SU Monotherapy
≥2 months Superiority
Submaximal SU GLY 7.5 mg o.d. + SAXA 2.5 mg o.d.† GLY 7.5 mg o.d. + SAXA 2.5 mg o.d.†

HbA1c ≥7.5%–≤10.0%
Superiority
to Enroll
MFPG ≥140 mg/dL or GLY 7.5 mg o.d. + SAXA 5 mg o.d.†
GLY 7.5 mg o.d. + SAXA 5 mg o.d.†
MFWBG ≥131 mg/dL
and HbA1c ≥7.0% to
Randomize

•92% reached maximum allowed dose of Glyburide in the short term phase (UP-GLY) - per the protocol titration
(UP-
criteria

†If
rescue criteria was met in short-term phase, add metformin 500–2500 mg TDD and enter LTE phase;
metformin rescue also available in the LTE phase.
MFPG = mean fasting plasma glucose; MFWBG = mean fasting whole blood glucose; o.d. = once daily.


HbA1C Adjusted Mean Change from Baseline
at Week 24 (LOCF)
Saxagliptin (mg) + Gly
Dose 2.5 5 Pbo + UP-Gly
n= 246 250 264
Baseline Mean 8.36 8.48 8.44
0.2
+0.1

0.0

Δ HbA1C (%) -0.2
with 95% CI

-0.4

-0.5
-0.6
-0.6
p <.0001
-0.8 p <.0001


Fasting Plasma Glucose Adjusted Mean
Dose 2.5 5 Pbo + UP-Gly
n= 247 252 265
170.1 175.0
Baseline Mean (mg/dL) 174.4
5.0

0.7
0.0

Δ FPG (mg/dL)

-5.0
with 95% CI
-7.1
-10.0
-9.7
p = .0218
-15.0 p = .0020


Postprandial Glucose AUC Adjusted Mean
2.5 5 Pbo + UP-Gly
Dose
190 195 204
n=
49124 50342 51801
Baseline Mean
(mg min/dL)

1196
1500

-500

Δ PPG AUC
(mg min/dL) -2500

CV181040 – Figure 7.3.3
with 95% CI

-4500 -4296
-5000
p <.0001
-6500 p <.0001


Most Common (≥5%) Reported Adverse Events
During 24-Week Treatment
Pbo
Saxa 2.5 mg Saxa 5 mg All Saxa
+ Up-Gly
+ Gly + Gly + Gly
N = 267
N = 248 N = 253 N = 501
Total subjects with AE 186 (75.0) 183 (72.3) 369 (73.7) 205 (76.8)
Adverse Events (≥5%)*
Urinary tract infection 13 (5.2) 27 (10.7) 40 (8.0) 22 (8.2)
Upper respiratory tract 11 (4.4) 16 (6.3) 27 (5.4) 18 (6.7)
infection
Influenza 13 (5.2) 10 (4.0) 23 (4.6) 16 (6.0)
Diarrhoea 14 (5.6) 10 (4.0) 24 (4.8) 14 (5.2)
Back pain 12 (4.8) 15 (5.9) 27 (5.4) 12 (4.5)
Pain in extremity 11 (4.4) 9 (3.6) 20 (4.0) 15 (5.6)
Headache 19 (7.7) 19 (7.5) 38 (7.6) 15 (5.6)
Cough 13 (5.2) 10 (4.0) 23 (4.6) 13 (4.9)
Hypertension 9 (3.6) 16 (6.3) 25 (5.0) 6 (2.2)
*Excludes Hypoglycemia

Hypoglycemic events were reported in 13.3% [33/248], 14.6% [37/253] of subjects in the
•
SAXA 2.5-mg & 5-mg treatment groups vs Up-Gly (10.1% [27/267]). The differences were
not statistically significant


Conclusions
In patients with type 2 diabetes not achieving glycemic control
on submaximal doses of glyburide monotherapy, the addition
of saxagliptin once daily provided statistically significant and
clinically meaningful reductions in the key parameters of
glycemic control in contrast to up-titrated glyburide
monotherapy.
More than twice as many patients treated with the combination
of saxagliptin and submaximal dose of glyburide achieved
target HbA1c <7.0% compared with up-titrated glyburide.
Improvements in glycemic parameters with the addition of
saxagliptin to a submaximal dose of glyburide were achieved
without any significant increases in hypoglycemia.
The administration of saxagliptin in combination with
submaximal doses of glyburide for up to 24 weeks was
generally well tolerated.


Saxagliptin Conclusion – EASD Highlights
Clinically Meaningful Reductions in
All Key Measures of Glucose Control Studied
Given in combination with metformin as an initial therapy, 5mg
saxagliptin demonstrated A1c reductions of 2.5% from baseline
– In patients with very high (≥10%) A1c’s, saxagliptin 5mg plus
metformin demonstrated A1c reductions of 3.3% from
baseline
When added to TZD, saxagliptin 5mg demonstrated A1c reduction
of 0.9% from baseline
When given in combination with an SU, saxagliptin 5mg
demonstrated A1c reduction of 0.6%
– No statistically significant increase in hypoglycemia
Saxagliptin also produced significant reductions in FPG and PPG
Saxagliptin was well tolerated in all usage situations

29

EASD 2008 Highlights
Investor Teleconference
Sept 9, 2008

30

bristol myerd squibb European Association for the Study of Diabetes (EASD) Highlights

Empfohlen

Empfohlen

Weitere ähnliche Inhalte

Ähnlich wie bristol myerd squibb European Association for the Study of Diabetes (EASD) Highlights

Ähnlich wie bristol myerd squibb European Association for the Study of Diabetes (EASD) Highlights (20)

Mehr von finance13

Mehr von finance13 (20)

Kürzlich hochgeladen

Kürzlich hochgeladen (20)

bristol myerd squibb European Association for the Study of Diabetes (EASD) Highlights