orlando, 28 june 2010 - roche8902db88-cd90-4456-8d3e-e3c8a869805a/en/... · tzd =...

Investor science event from ADA 2010

Orlando, 28 June 2010

Forward-looking statements

This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similarexpressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others:1 pricing and product initiatives of competitors;2 legislative and regulatory developments and economic conditions;3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products,

including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products;

6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation;10 loss of key executives or other employees; and11 adverse publicity and news coverage.

Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche’s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche.

Please see www.roche.com for full information on Roche products mentioned.

2

Introduction

Dr. Karl Mahler, Head of Investor Relations

Investor science events at major medical meetingsAt least five events will highlight Roche’s leadership

4

RG1594(ocrelizumab)ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis)

October 2010Gothenburg, Sweden

Avastin, RG3502(T-DM1), etc.ESMO (European Society for Medical Oncology)

October 2010Milan, Italy

Diagnostics review & updateAACC (American Association for Clinical Chemistry)

26 July 2010Anaheim, USA

Franchise update CardioMetabolism, RG1583(taspoglutide), etc.

ADA (American Diabetes Association)28 June 2010Orlando, USA

Avastin, MabThera/Rituxan, RG3502(T-DM1), RG1273(pertuzumab), etc.

ASCO (American Society of Clinical Oncology)

6 June 2010Chicago, USA

Key assets / newsflowMeetingDate / location

Steady flow of important clinical data & results

Taspoglutide & the GLP-1 class: Product attributes along three distinct dimensions

5

Taspoglutide:Potential for best-in-class

convenience

Convenience(Injection frequency (BID, QD or QW), need for corrections,

simple injection vs reconstitution, needle gauge)

Efficacy(HbA1c, % pts reaching <7.0, FBG, weight loss, persistence of efficacy, increased insulin secretion, beta cell function)

Safety / Tolerability(Hypoglycemia, nausea, vomiting, diarrhea,

hypersensitivity, pancreatitis, thyroid cancer)

Taspoglutide:Work ongoing to refine profile

All GLP-1s have specific safety / tolerability challengesTaspoglutide:

Robust, consistent efficacy

Investor science event from ADA 2010Programme 28 June 2010 6.30 - 8.00 pm

• Introduction– Dr. Karl Mahler, Head of Investor Relations

• Franchise overview: CardioMetabolism– Dr. Fouzia Laghrissi Thode, Global Product Strategy Head for Metabolism and Anemia

• Taspoglutide: Overview of data at ADA 2010– Dr. Bruce Cooper, Head of Global Medical Affairs

• Taspoglutide: T-emerge 5 - comparison w/insulin glargine– Prof. Dr. med. Michael Nauck

• Taspoglutide: Next steps– Dr. Bruce Cooper, Head of Global Medical Affairs

• Questions & Answers– Moderator: Dr. Karl Mahler

Expected duration up to 1½ hour

Dinner reception

6

Franchise overview: CardioMetabolism

Dr. Fouzia Laghrissi Thode, Global Product Strategy Head for Metabolism and Anemia

8

Recent announcementRisk mitigation plan implemented

• To date, out of approximately 3,000 taspoglutide-treated patients in the phase III programme, a total of 23 cases of serious hypersensitivity reactions have been reported as related to taspoglutide by investigators (i.e. incidence < 1%)

• Roche has identified a potential association between anti-drug antibodies (ADAs) and an increased risk for patients to experience serious hypersensitivity reactions

• ADA levels will be routinely monitored and patients that develop pre-specified ADA levels will discontinue treatment and continue to be monitored in the trial

Serious hypersensitivity reactions

• Hypersensitivity reactions judged by investigators as serious

– Anaphylaxis or other systemic allergic reactions (ie, urticaria, angioedema)

• Anaphylaxis symptoms included:

– Cutaneous reactions (skin and/or mucosa): e.g., urticaria , angioedema

– Gastrointestinal: e.g., prolonged nausea and/or vomiting

– Respiratory: e.g., dyspnea

– Cardiovascular: e.g., blood pressure and/or heart rate changes

• No anaphylactic shock

• All patients recovered without complications

– Only one patient hospitalized overnight for observation

– Some patients were treated with antihistamines, steroids and one case was treated with adrenaline

10

Our commitment to CardioMetabolism

10

Development• T-emerge most

comprehensive program in diabetes to date

• Dalcetrapib largest patient trial undertaken by Roche Pharma

• Aleglitazar – initiating in 24 countries

CardioMetabolism franchise • Building capabilities

• Establishing leadership in

CardioMetabolism

Research • gRED and pRED

programs

• Active partnering

Preparing for mid and long-term success in new disease area Preparing for mid and longPreparing for mid and long--term success in new disease area term success in new disease area

11

Value for patients

Dalcetrapib

• Improved CV outcomes by treating the underlying disease of atherosclerosis

Taspoglutide

• Glycemic control

• Minimizing hypoglycemia

• Reducing weight

Aleglitazar

• Unique profile to reduce CV risk in Type 2 diabetes

12

Development programs to deliver first or best in class

dal-OUTCOMES

15,600 patients

dal-HEART

ALECARDIO6,000 patients

ALECARDIO

dal-PLAQUE2

900 patients

dal-PLAQUE

130 patients

dal-VESSEL

450 patientsALENEPHRO

300 patients

Raising HDL through CETP modulation to reduce cardiovascular risk

12

CV risk reduction for patients with type 2 diabetes post-ACS

RG1658(dalcetrapib)dal-OUTCOMES phase III study now fully recruited

• Phase III dal-OUTCOMES

– 15,600 CHD2 pts w/recent ACS3

– Best standard of care +/- dalcetrapib 600 mg qd

– Event-driven trial

• First patient in Q2-08, last patient in Q2-10

• Expected interim efficacy analysis in Q3-11 (event-driven), expected regulatory filing in 2013

• Targeted indication: Prevention of cardiovascular event in very high risk patients

• Primary outcomes study supported by secondary phase II/III studies; dal-VESSEL, dal-PLAQUE, dal-PLAQUE2

131Roche epidemiology prevalence projection based on National Center for Health Statistics’ NHANES data (2009) 2CHD=Coronary heart disease 3ACS=Acute coronary syndrome

Target population by risk status1

RG1439(aleglitazar)ALECARDIO phase III study enrolling

• Phase III ALECARDIO in 24 countries

– 6,000 T2D2 pts hospitalized w/ACS3

– Best standard of care +/- aleglitazar 150 μg qd

– Event-driven trial

• First patient in Q1-10; enrollment on track

• Regulatory filing expected in 2014

• Targeted indication: Prevention of cardiovascular event in Type 2 diabetes patients post ACS

141Patients with T2D2 and ACS3 (excl CHF NYHA II-IV) 2T2D=Type 2 diabetes 3ACS=Acute Coronary Syndrome

Target population growing fast1

Taspoglutide: Overview of data at ADA 2010

Dr. Bruce Cooper, Head of Global Medical Affairs

16

Phase 3 Program: Over 6000 Patients, >1000 sites, ≈ 50 Countries

BID = twice daily; BMI = body mass index; Met = metformin; QW = once weekly; SU = sulfonylurea;TZD = thiazolidinedione. *10 mg taspoglutide QW for 4 weeks followed by 20 mg QW.

Study Name Patient Population Sample Size Taspoglutide Comparator

T-emerge 1Inadequately controlled

on diet & exercise 373

10 mg QW20 mg QW*

Placebo

T-emerge 2 Inadequately controlled with

Met, TZD, or Met + TZD 1189

10 mg QW20 mg QW*

Exenatide BID

T-emerge 3Inadequately controlled with pioglitazone + Met

326 10 mg QW20 mg QW*

Placebo


with Met 666

10 mg QW20 mg QW*

Sitagliptin Placebo


on Met + SU; SU withdrawn at pre-randomization

104910 mg QW20 mg QW*

Insulin glargine


with SU ± Met 760

10 mg QW20 mg QW*

Pioglitazone


with Met (high BMI) 305 20 mg QW* Placebo

T-emerge 8Patients with higher cardiovascular risk

2000 20 mg QW* Placebo

17

Taspoglutide in T2DM: Headline Results from ADA

Study Description Headline Results/status

H2H vs. exenatide Primary endpoint met: Superior HbA1creduction versus twice-daily exenatide

Vs. placebo, monotherapy

Primary endpoint met: Superior HbA1creduction versus placebo

H2H vs. sitagliptin vs. placebo

Primary endpoint met: Superior HbA1c reduction versus sitagliptin

H2H vs. insulin glargine Primary endpoint met: Non-inferior HbA1creduction versus insulin glargine

Vs. placebo, obese T2D patients

Primary endpoint met: Superior HbA1c reduction versus placebo

EarlyDisease

TreatmentNaïve

EarlyDisease

AdvancedDisease

EarlyDisease

T-emerge Included Treatment Naïve T2D Patients With Early & Advanced Disease

18

Study Design for the Active-Controlled Studies: T-emerge 2, 4‡, 5, and 6

*Patients randomized to taspoglutide 20 mg QW will receive taspoglutide 10 mg QW for 4 weeks followed by the 20 mg QW dosing. †Active comparator: TE-2, exenatide; TE-4, sitagliptin; TE-5, insulin glargine; TE-6, pioglitazone.‡TE-4: sitagliptin active comparator and also includes placebo-controlled group.

Taspoglutide formulation • Once-weekly SC injection• 29-g needle• Prefilled syringe

Taspoglutide 20 mg QW Taspoglutide 20 mg QW

Taspoglutide 10 mg QWTaspoglutide 10 mg QW

Follow-up

Primary Endpoint

24 weeks 28-week extension

Week 240 weeks 52 weeks

4*

Patie

nt s

cree

ning

≤4

Active comparator†Active comparator†

10 mg*

2

2-yearlong-term extension

19

Study Design for the Placebo-Controlled Studies: T-emerge 1†, 3, and 7‡

*Patients randomized to taspoglutide 20 mg QW receive taspoglutide 10 mg QW for 4 weeks followed by the 20 mg QW dosing.†TE-1: 3-week patient screening and 2-week placebo run-in.‡TE-7 trial does not include taspoglutide 10 mg QW dose group.

Taspoglutide formulation•Once-weekly SC injection•29-g needle•Prefilled syringe


Taspoglutide 10 mg QW

Placebo Taspoglutide 10 mg QWTaspoglutide 20 mg QW10 mg*

10 mg*

Taspoglutide 10 mg QW

Follow-up

Primary Endpoint



4*

† Pat

ient

scr

eeni

ng

≤4 2

20

Overall Baseline Demographics and Disease Characteristics

Mean (SD) unless specified

TE-1(N=354)

TE-2(N=1149)

TE-4(N=636)

TE-5(N=1028)

TE-7(N=292)

Men – n (%) 130 (37) 608 (53) 352 (55) 549 (53) 119 (41)

Age, y 55 (10) 56 (10) 56 (10) 58 (9) 54 (10)

Weight, kg 86.8 (18.0) 94.4 (19.2) 92.4 (19.3) 90.8 (19.5) 102.5 (18.1)

BMI, kg/m2 32.3 (5.1) 33.4 (5.2) 32.5 (5.1) 32.4 (5.3) 36.7 (4.9)

HbA1c, % 7.60 (1.01 8.07 (0.91) 7.96 (0.87) 8.28 (0.90) 7.55 (0.84)

HbA1c baseline ≥8.0% ‐ n (%) 108 (31) 572 (50) 281 (44) 610 (59) 83 (28)

FPG, mg/dL 158 (45) 178 (46) 173 (46) 201 (52) 130 (37)

Diabetes duration, y 2.4 (2.5) 6.6 (5.4) 5.9 (4.7) 9.1 (6.0) 5.1 (4.2)

History of CV disorders* – n (%) 55 (15) 183 (16) 99 (15) 198 (19) 49 (16)

Intent-to-treat population. *Patients in the safety population with ≥1 cardiovascular disorder.

21

Primary Endpoint: HbA1c Change From Baseline After 24 Weeks of Treatment

Baseline (%) 7.6 7.5 7.7 8.1 8.1 8.1 8.0 8.0 8.0 7.9 8.2 8.3 8.3 7.5 7.5

Exen

atid

e

Sita

glip

tin

Insu

lin g

larg

ine

Taspoglutide 10 mg QW Active comparatorPlacebo Taspoglutide 20 mg QW

*

*†

†*†

*†

*

TE-1Monotherapy

TE-2Metformin, TZD, or both

TE-4Metformin

TE-5Metformin, SU withdrawal

TE-7Metformin

LOCF = last-observation-carried-forward; LSMean = least square mean; SE = standard error. *P<0.001 vs placebo; †P<0.001 vs active comparator. Intent-to-treat population; LOCF analysis.TE-5: Sulfonylurea treatment withdrawn prior to randomization for all patients.

22

Time Course Example: TE-1 HbA1c Change From Baseline Over 24 Weeks of Treatment

**

Taspoglutide 10 mg QW(n=112)


Placebo(n=115)

LSMean = least square mean; SE = standard error.*P<0.001 vs placebo. Intent-to-treat population; last-observation-carried-forward analysis.

23

Percentage of Patients Reaching Target HbA1c <7% After 24 Weeks of Treatment

*Baseline entry criterion for TE-1 and TE-7 trial was HbA1c ≥6.5%; this analysis excluded patients from TE-1 and TE-7 with baseline HbA1c <7%.

Sita

glip

tin

Gla

rgin

e

Exen

atid

e


TE-1*Monotherapy


TE-4Metformin


TE-7*Metformin

24

Fasting Plasma Glucose (mg/dL) Change From Baseline After 24 Weeks of Treatment

Baseline (mg/dL) 156 158 162 179 177 178 174 176 174 169 190 190 203 158 163

Exen

atid

e

Sita

glip

tin

Insu

lin g

larg

ine

**

‡

*‡

*

†

‡

‡

*‡


TE-1Monotherapy


TE-4Metformin


TE-7Metformin

LSMean = least square mean; SE = standard error; Intent-to-treat population; LOCF analysis*P<0.001 vs placebo; †P<0.01 vs active comparator; ‡P< 0.001 vs active comparator. TE-5: Sulfonylurea treatment withdrawn prior to randomization of all patients. Insulin dose titrated to FPG target.

Time Course Example: TE-1 Fasting Plasma Glucose Over 24 Weeks of Treatment



Placebo(n=115)

*P<0.001 vs placebo. Intent-to-treat population; last-observation-carried-forward analysis.

FPG

(m

g/dL

) (M

ean ±

SE)

**

26

Body Weight Change From Baseline After 24 Weeks of Treatment

Glar = insulin glargine; LSMean = least square mean; SE = standard error; Sita = sitagliptin; TZD = thiazolidinedione.*P<0.05 vs placebo; †P<0.05 vs active comparator; ‡P<0.01 vs placebo; ¶P<0.001 vs placebo or vs active comparator. Intent-to-treat population; last-observation-carried-forward analysis.

Baseline (kg) 87 88 85 95 93 95 91 94 92 93 90 91 91 101 104

Exen

atid

e

Sita Glar

¶

*

† ‡

¶

¶

¶

‡


TE-1Monotherapy


TE-4Metformin


TE-7Metformin

27

Time-Course of Body Weight Change From Baseline Over 24 Weeks of Treatment

LSMean = least square mean; SE = standard error.*P<0.05 vs placebo; †P<0.05 vs active comparator; ‡P<0.01 vs placebo; §P<0.001 vs placebo or vs active comparator.Intent-to-treat population; last-observation-carried-forward analysis.

TE-1 TE-2 TE-4 TE-5 TE-7

Cha

nge

in b

ody

wei

ght (

kg) f

rom

bas

elin

e (L

SMea

n ±

SE)

Sitagliptin Insulin glargineExenatide

*

† †

§

§

§

‡

‡

Diet & exercise


28

Body Weight Loss Responder Rates After 24 Weeks of Treatment: ≥5%

Sita

Gla

r

Exen

atid

e


Glar = insulin glargine; Sita = sitagliptin; TZD = thiazolidinedione.Intent-to-treat population; last-observation-carried-forward analysis.

TE-1Monotherapy


TE-4Metformin

TE-5Metformin

TE-7Metformin

29

Safety Overview at 24 Weeks

• Incidence of nausea: 26-47%

• Incidence of vomiting: 17-28%

• Injection site reactions generally mild to moderate and infrequently lead to discontinuation (1.4-5%)

• % withdrawals due to all adverse events

10mg: 9-17%20mg: 21-28%Control: 7-16%

• % withdrawals due to nausea or vomiting (T-emerge 2; H2H vs. exenatide)

10mg: 4.1%20mg: 7.6%Exenatide: 6.5%

30

Example: TE-2Number of Episodes of Nausea or Vomiting Over 24 Weeks

% o

f pat

ient

s

Nausea Vomiting

# of Episodes

Withdrawals due to nausea or vomiting: exenatide: 6.5%, taspoglutide 10 mg QW: 4.1%, taspoglutide 20 mg QW: 7.6%

# of Episodes

Exenatide 10 μg BIDTaspoglutide 10 mg QW Taspoglutide 20 mg QW

Safety population.

31

Example: TE-2Weekly Incidence of Nausea and Vomiting Over 24 Weeks

Safety population

Up-titration from 10 mg to 20 mg

Up-titration from 10 mg to 20 mgNausea

Vomiting

Exenatide 10 μg BID Taspoglutide 10 mg QW Taspoglutide 20 mg QW

86% and 83% of vomiting occurred on Day of Injection for taspoglutide 10 mg QW and 20 mg QW, respectively

32

Summary

• T-emerge program studied taspoglutide across a wide spectrum of patient types (including treatment-naive and patients with early disease and advanced disease) and versus 4 active comparators (exenatide, sitagliptin, pioglitazone, and even the highest dose of insulin glargine used in a GLP-1 registration study)

• In the T-emerge Clinical Development Program, taspoglutide demonstrated evidence of consistent glycemic control with low risk of hypoglycemia and significant weight loss in a ready-to-use weekly injection

• As has been seen with other GLP-1 receptor agonists, the most frequently reported adverse events with taspoglutide were related to gastrointestinal tolerability

* Based on T-emerge results to-date at 24 weeks

Taspoglutide: T-emerge 5 - comparison w/insulin glargine

Prof. Dr. med. Michael Nauck

34

Michael Nauck,1 Edward Horton,2 Mirjana Andjelkovic,3Javier Ampudia-Blasco,4 Mark N. Boldrin,5 Raffaella Balena3

1Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany 2Joslin Diabetes Center, Boston, MA, United States3F.Hoffmann-La Roche, Basel, Switzerland4Clinic University Hospital, Valencia, Spain5Roche Pharmaceuticals, Nutley, NJ, United States

T-emerge 5

Taspoglutide, a Once-Weekly Human GLP-1 Analog, Provides Comparable Glycemic Control to Insulin Glargine,

with Superior Weight Loss and Less Hypoglycemia in Type 2 Diabetes: A Phase 3, Open-Label Trial (T-emerge 5)

35

Taspoglutide, a Once-Weekly Human GLP-1 AnalogPhase 3 Program: Over 6000 Patients

BID = twice daily; BMI = body mass index; Met = metformin; QW = once weekly; SU = sulfonylurea;TZD = thiazolidinedione. *10 mg taspoglutide QW for 4 weeks followed by 20 mg QW.

Study Name Patient Population Sample Size Taspoglutide Comparator

T-emerge 1 Inadequately controlled on diet & exercise 373 10 mg QW

20 mg QW* Placebo

T-emerge 2 Inadequately controlled with Met, TZD, or Met + TZD 1189 10 mg QW

20 mg QW* Exenatide BID

T-emerge 3 Inadequately controlled with pioglitazone + Met 326 10 mg QW

20 mg QW* Placebo

T-emerge 4 Inadequately controlled with Met 666 10 mg QW

20 mg QW*Sitagliptin Placebo


on Met + SU; SU withdrawn pre-randomization

1049 10 mg QW20 mg QW* Insulin glargine

T-emerge 6 Inadequately controlled with SU ± Met 760 10 mg QW

20 mg QW* Pioglitazone

T-emerge 7 Inadequately controlled with Met (high BMI) 305 20 mg QW* Placebo

T-emerge 8 Patients with higher cardiovascular risk 2000 20 mg QW* Placebo

36

Objectives of Study

Primary objectivePrimary objective

• To demonstrate non-inferiority of taspoglutide to insulin glargine on glycemic control (HbA1c) after 24 weeks of treatment in insulin-naive type 2 diabetic patients inadequately controlled with metformin and sulphonylurea combination therapy

Secondary objectivesSecondary objectives

• To assess the effects of taspoglutide on additional parameters of glycemic control, body weight, and cardiovascular risk factors after 24 weeks

• To assess the safety and the tolerability of taspoglutide after 24 and 52 weeks

37

Study Design: Randomized, Open-label, Parallel Group, Active-Controlled

*Forced titration scheme to target FPG ≤ 110 mg/dL (6.1 mmol/L)Patients will receive taspoglutide 10 mg QW for 4 weeks followed by the 20 mg QW dosing

Study population•HbA1c ≥ 7.0% and ≤ 10.0%•Stable doses for ≥ 12 weeks of metformin (≥1500 mg/day or individual maximally tolerated dose) and sulfonylurea (any dose)•BMI ≥ 25 (> 23 for Asians) and ≤ 45 kg/m2

•Stable weight ± 5 % for at least 12 weeks


Taspoglutide 10 mg QWTaspoglutide 10 mg QW


4*

Pat

ient

scr

eeni

ng

≤ 4


Insulin glargineInsulin glargine*

10 mg

Follow up

Long-term extension up

to 3 years

Primary Endpoint

Sulfonylurea treatment stopped 5 days prior to start of study

38

Baseline Demographic Characteristics (N=1028)

Mean (SD) unless specified

Taspoglutide Taspoglutide 10 mg QW10 mg QW

(n=361)(n=361)

TaspoglutideTaspoglutide20 mg QW20 mg QW

(n=348)(n=348)

Insulin Insulin glargineglargine(n=319)(n=319)

Age, years 58 (10) 57 (9) 58 (9)BMI, kg/m2 32.1 (5.3) 32.4 (5.3) 32.7 (5.2)HbA1c, % 8.2 (0.9) 8.3 (0.9) 8.3 (0.9)

HbA1c baseline > 8.0%, n (%)

208 (58) 206 (59) 196 (61)

FPG, mg/dL 200 (54) 199 (52) 202 (51)Diabetes duration, years 9 (6) 9 (6) 9 (6)

Intent-to-treat population.

39

Primary Endpoint: HbA1c Over 24 Weeks of Treatment

LSMean = least square mean; SE = standard error.Intent-to-treat population; last-observation-carried-forward analysis.

Insulin glargine*(n = 319)

Taspoglutide 10 mg QW(n = 361)

Taspoglutide 20 mg QW(n = 348)

Non-inferiority/Superiority Summary of HbA1c Change from Baseline at Week 24 (LOCF, ITT)

Non-inferiority margin

Treatment difference for HbA1c (%, 95% CI)

-0.5 -0.4 -0.3 -0.2 -0.1 0

Taspoglutide 10 mg vs insulin glargine

Taspoglutide 20 mg vs insulin glargine

0.07

-0.06 0.21

-0.14

-0.28 -0.01

0.1 0.2 0.3 0.4

*Final mean daily insulin glargine dose = 36 IU

-0.77

-0.98

-0.84

40

Percentage of Patients Reaching Target HbA1cAfter 24 Weeks of Treatment

Intent-to-treat population; last-observation-carried-forward analysis.*Final mean daily insulin glargine dose = 36 IU.

HbA1c < 7.0% HbA1c ≤ 6.5%

Insulin glargine*Taspoglutide 10 mg QW Taspoglutide 20 mg QW

n= 361 348 319 361 348 319

41

-3.0

-2.0

-1.0

-4.0

0.0

mm

ol/L

*P < 0.001 vs insulin glargine.Intent-to-treat population; LOCF analysis.

Taspoglutide 10 mg(baseline=190 mg/dL)

Taspoglutide 20 mg (baseline=190 mg/dL)

Cha

nge

in F

PG (m

g/dL

) fro

m b

asel

ine

(LSM

ean

±SE

)

Insulin glargine(baseline=203 mg/dL)

-

-

-

-

* -

*

Insu

lin D

ose

(IU/d

ay) (

LSM

ean ±

SD)

†Forced titration scheme to target FPG ≤ 110 mg/dL (6.1 mmol/L)

Time (weeks)

10

19

2730

3536

0

10

20

30

40

50

60

0 4 8 12 16 2420

Daily Dose of Insulin Glargine (IU)†

Change in FPG and insulin titration

42

Two-hour Postprandial Glucose (PPG) (mg/dL):Corrected for Fasting Glucose at Baseline and Week 24*

*Subset of patients†Glucose level at 2-hr post-meal minus fasting glucose at 0 hr



Insulin glargine(n=35)

BaselineWeek 24

2-H

our p

ost-m

eal g

luco

se(m

g/dL

) (m

ean ±

SD)†

Change from baseline for PPG†

(mg/dL; mean [95% CI])

-14.7

-27.5 -1.9

-12.4

-26.3 1.5

-25 -20 -15 -10 -5 0 5 10 15

6.4

-5.6 18.5

-30 20

43

Change in Body Weight Over 24 Weeks of Treatment

*P < 0.001 vs insulin glargine. Intent-to-treat population; last-observation-carried-forward analysis. †Final mean daily insulin glargine dose = 36 IU.

*

*

*

*

90.2 91.5 90.6Baseline (kg)

Cha

nge

in b

ody

wei

ght (

kg) f

rom

ba

selin

e (L

SMea

n ±

SE)

Insulin glargine†

(n=319)Taspoglutide 10 mg QW(n=361)


44

Safety Overview During the 24 Week Treatment Period

Taspoglutide 10 mgTaspoglutide 10 mgN=364N=364n (%)n (%)


Insulin Insulin glargineglargineN=322N=322n (%)n (%)

Total pts with > 1 AE 285 (78.3) 301 (85.8) 187 (58.1)

Serious AEs 14 (3.8) 16 (4.6) 11 (3.4)

AEs leading to discontinuation 41 (11.3) 61 (17.4) 7 (2.2)

Deaths – 1 (0.3)1 2 (0.6)1

Hypoglycemia*

Reported 18 (4.9) † 21 (6.0) † 56 (17.4)

Confirmed (< 55 mg/dL) 1 (0.3) 3 (0.9) 10 (3.1)

Severe – – –

*Reported: symptoms without or without confirmation by measured plasma glucose concentration.Confirmed: symptoms accompanied by measured plasma glucose concentration ≤55 mg/dL.Severe: requiring assistance to actively administer carbohydrate, glucagon, or other resuscitative actions.

† p < 0.001 vs. insulin glargine Safety population.1Non-drug related

45

Summary of Adverse Events With ≥ 5 % Incidence Rate

Taspoglutide 10 mgN=364n (%)

Taspoglutide 20 mgN=351n (%)

Insulin glargineN=322n (%)

Gastrointestinal disordersNausea 143 (39.3) 159 (45.3) 6 (1.9)Vomiting 72 (19.8) 80 (22.8) 4 (1.2)Diarrhea 48 (13.2) 46 (13.1) 18 (5.6)

General disorders and administration site conditionsInjection site nodule 39 (10.7) 55 (15.7) -Injection site pruritus 26 (7.1) 17 (4.8) 1 (0.3)

Metabolism and nutrition disordersHypoglycemia 18 (4.9) 21 (6.0) 56 (17.4)Decreased appetite 30 (8.2) 35 (10.0) 2 (0.6)

Infections and infestationsNasopharyngitis 20 (5.5) 20 (5.7) 25 (7.8)

Nervous system disordersHeadache 25 (6.9) 30 (8.5) 16 (5.0)Dizziness 19 (5.2) 16 (4.6) 7 (2.2)

Safety population

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Summary of Patients Withdrawn, by Reason

Safety population*For individual adverse events, only those occurring ≥ 0.5% in any group are reported.



Insulin Insulin glargineglargineN=322N=322n (%)n (%)

Withdrawals for any reason 76 (20.9) 74 (21.1) 29 (9.0)Adverse event* 32 (8.8) 47 (13.4) 3 (0.9)

Nausea 9 (2.5) 19 (5.4) –Vomiting 7 (1.9) 9 (2.6) –Diarrhea 2 (0.5) 2 (0.6) –Injection site reaction 2 (0.5) 2 (0.6) –Fatigue – 2 (0.6) –Hypersensitivity 1 (0.3) 3 (0.9) –Hyperglycemia 9 (2.5) 6 (1.7) 3 (0.9)

Withdrew consent 15 (4.1) 14 (4.0) 8 (2.5)Failure to return 3 (0.8) 1 (0.3) 7 (2.2)Insufficient therapeutic response 18 (4.9) 8 (2.3) 4 (1.2)Refused treatment did not cooperate 4 (1.1) 2 (0.6) 4 (1.2)Administrative/other 2 (0.5) - 2 (0.6)Violation of selection criteria at entry 2 (0.5) 1 (0.3) -Death - 1 (0.3) 1 (0.3)

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Number of Episodes of Nausea or Vomiting Over 24 Weeks%

of p

atie

nts

Nausea Vomiting

Safety population.

# of Episodes

Withdrawals due to nausea or vomiting: taspoglutide 10 mg: 4% taspoglutide 20 mg: 7% insulin glargine: 0%

# of Episodes

Insulin glargine(n = 322)

Taspoglutide 10 mg(n = 364)

Taspoglutide 20 mg(n = 351)

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Weekly Incidence of Nausea and Vomiting Over 24 WeeksInsulin glargineTaspoglutide 10 mg Taspoglutide 20 mg



Nausea

Vomiting

81 % and 84 % of vomiting occurred on day of injection for taspoglutide 10 mg and 20 mg, respectively.

Safety population

49

Summary

• Taspoglutide demonstrated non-inferior HbA1c lowering (- 0.98 % vs. - 0.84 %) and better HbA1c goal achievement of < 6.5% (24 % vs. 14 %) vs. well titrated insulin glargine (mean dose = 36 IU/d)

• Incidence of reported hypoglycemia was 4.9-6.0% for taspoglutide vs. 17.4 % for insulin glargine

• Taspoglutide demonstrated significant weight loss of - 4.1 kg (vs. - 0.4 kg for insulin glargine)

• Most frequently reported adverse events for taspoglutide were gastrointestinal in nature

• Among patients reporting nausea or vomiting, there was predominantly a single episode that infrequently led to discontinuation and tended to occur early in treatment on the day of injection

Conclusions

• As with other GLP-1 receptor agonists, the most common adverse events with taspoglutide are related to GI tolerability

• In patients with inadequate glycemic control on metformin and sulfonylurea, replacing a sulfonylurea with taspoglutide demonstrated comparable HbA1c lowering and target HbA1c control with a low risk of hypoglycemia and weight loss as compared to insulin glargine

Taspoglutide: Next steps

Dr. Bruce Cooper, Head of Global Medical Affairs

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Taspoglutide: The situation today

Our challenge

– Filing delayed a minimum of 12 to 18 months

– Higher than expected incidence of serious hypersensitivity (<1%)

– Gastrointestinal tolerability profile

Our response

– Risk mitigation plan to protect the safety of patients in the phase III programme

– Investigating root cause and assessing potential solutions to address hypersensitivity reactions

– Further studies to optimise the gastrointestinal profile

– Ongoing analysis of 52 weeks data from the overall T-emerge programme

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52

What we know: Efficacy

• Combined benefits of robust A1c reduction, with low risk of hypoglycemia and clinically important weight loss in a simple ready-to-use weekly injection

• Consistent results across all studies and across a wide spectrum of Type 2 diabetes patients

• Statistically superior A1c reduction vs exenatide BID, sitagliptin and metformin –getting up to 71% of patients to ADA HbA1c treatment goal

• Superior combined benefit to a well-titrated dose of insulin glargine (36IU) with significantly more patients reaching target HbA1c with less hypoglycemia and superior weight loss

• Both 10mg and 20mg doses are effective – 20mg has higher weight loss

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What we know: Safety & tolerability

• The type of adverse events reported are in line with the GLP-1 class

• Nausea and vomiting were higher than the targeted product profile, however, in general these events were mild to moderate, occurred early in the treatment course, usually on the day of injection and predominantly as a single episode

• Serious hypersensitivity reactions occurred late in the program and is being investigated and addressed with a risk mitigation plan

• Cross-study comparisons with other GLP-1s are valid only in well-conducted head to head trials

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The path forward - I

• CV safety study T-emerge 8 continues to recruit

• Patients who develop anti-drug antibody levels above a pre-specified limit will be withdrawn from a study and continue to be followed up

• Hypersensitivity investigationsAdditional assessments of affected patientsAdditional antibody assessments – including profile of other GLP-1’sSearch for any factors that can be addressed

54

Continued commitment to patient safety and transparency with decisions based on consultation with scientific,

clinical and regulatory experts, and data analysis

55

The path forward - II

• Studies planned to optimise gastrointestinal tolerability

– E.g. dose timing, associated meal, site of injection

• Extension studies continue - data from T-emerge 2 at 52 weeks show:– HbA1c superiority for both doses vs. exenatide– Overall incidence of gastrointestinal adverse events and the incidence of

adverse events leading to withdrawal were higher in each taspoglutide arm– Analysis of the data ongoing

• Additional 52 weeks data from T-emerge trials are expected soon and will help us better inform the safety, tolerability and efficacy profile of taspoglutide

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Continued commitment to patient safety and transparency with decisions based on consultation with scientific,

clinical and regulatory experts, and data analysis

Questions & Answers

Moderator: Dr. Karl Mahler

57

We Innovate Healthcare

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