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46th ASCO Annual Meeting

Roche Analyst Event

Sunday, June 6, 2010 - Chicago

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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 similar expressions 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; and

11. 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.

For marketed products discussed in this presentation, please see full prescribing information at www.roche.com or www.gene.com.

All mentioned trademarks are legally protected.

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Agenda

• Setting the standard of care in oncology

– Pascal Soriot, Chief Operating Officer Roche Pharmaceuticals

• Avastin in ovarian cancer, GOG-0218 study

– Jakob Dupont, M.D., Associate Group Medical Director, Avastin Global Clinical Development, Genentech

• Overview of Avastin development program

– Stefan Frings, M.D., Avastin Franchise Director, Roche

• MabThera/Rituxan maintenance in previously untreated patients with follicular lymphoma (PRIMA study)

– Professor Gilles Salles, M.D., Ph.D., Principal Investigator of PRIMA study, Centre Hospitalier Lyon-Sud, France

• Summary and Q&A: Mondher Mahjoubi and Karl Mahler

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Setting the standard of care in oncology

Pascal Soriot, COO Roche Pharmaceuticals

5

Focus on improving the standard of care

Improve outcome with existing products

Clin

ical

ben

efit New products

• Roche’s own products• Combinations

Improving treatment within a class / product

Advances through medical breakthroughs / novel mechanisms

6

Our starting point: Superior clinical efficacyThe example of Avastin

mCRC mNSCLC mBC

1. Hurwitz, et al. NEJM 2004; 2. Saltz, et al. JCO 2008; 3. Sandler, et al. NEJM 2006; 4. Reck, et al. JCO 2009; 5. Gray, et al. JCO 2009; 6. Avastin SmPC; 7. Robert, et al. ASCO 2009; 8. Brufsky, et al, SABCS 2009; 9. Burger, et al, ASCO 2010; 10. Giantonio et al. JCO 2007

AVF2107g1

OS: HR=0.66p<0.001

NO169662

PFS: HR=0.83p=0.0023

E45993

OS: HR=0.79p=0.003

E21005

PFS: HR=0.48p<0.0001

AVAiL4

PFS: HR=0.75/0.82p=0.003/0.03

AVADO6

PFS: HR=0.67p=0.0002

RIBBON-17

PFS: HR=0.69/0.64p=0.0002/0.0001

Ovarian

GOG-02189

PFS: HR=0.717/0.645p=<0.0001

RIBBON-28

PFS: HR=0.78p=0.0072

E320010

OS: HR=0.75p=0.001

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Improving clinical outcome with existing products

Maximizing the clinical benefit

Longer treatment duration

Maintenance treatment

Treatment through Multiple Lines (TML)

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Bevacizumab 15 mg/kg

15 months

Carboplatin+Paclitaxel

Placebo

PlaceboBevacizumab

15 mg/kg

I

II

III

Arm



Avastin in 1st line ovarian cancerFirst clinical breakthrough in over a decade

Primary endpoint: Avastin+chemo followed by Avastin alone for up to 15 months significantly increased median PFS

Impact on ovarian cancer therapy*

2008

2018

*Decision Resources, May 2010

Longer treatment duration

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Treatment through Multiple Lines (TML)ARIES: Avastin benefit beyond progression in mCRC

ARIES study (n=1,547 patients)Median OS:

Avastin-based treatment: 27.5 months

Non-Avastin regimen: 18.7 months

Chemotherapy+Avastin→PD → Chemotherapy +/-Avastin

Design

FPI Q1 2006Status

Overall survivalPrimary Endpoint

5 mg/kg q2 weeks or 7.5 mg/kg q3 weeks

Avastin Dose

N=810# of Patients

Phase IIIML18147


Phase/Study

Metastatic Colorectal Cancer

Patient Population

TML prospective study

Enrollment completed June 2010


BRiTE registry (n=1,953 patients)Median OS:



Cohn, et al. ASCO 2010, Abstract #3596

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Rituxan helps patients stay in remission for longer

Transforming cancer into a chronic disease

• Follicular lymphoma incurable

Pattern of relapse and repeated therapy

• Disease control is the key treatment goal

• PRIMA - potentially changing the treatment paradigms

• Additional 2 years of treatment after induction therapy

PRIMA: 2-year maintenance treatment with Rituxanfollowing induction therapy with Rituxan and

chemotherapy

Maintenance treatment

Even

t-fr

ee r

ate

Rituxan maintenanceN=505

Time (months)

ObservationN=513

60 12 18 24 30 36 42

0.8

0.6

0.4

0.2

0

1.0 82%

66%

HR = 0.50 [95% CI= 0.39, 0.64] p-value < 0.0001

1111

Avastin

Anti-P

IGF

Anti-N

RP

1

Anti-EG

FL7

G-secretase

inh

Herceptin

Pertuzum

ab

T-DM

1

Tarceva

GA

201

Xeloda

MabThera/R

ituxan

Anti-C

D20/G

A101

BR

AF

Inh

RG

7167/CIF (M

EKi)

RG

7420(M

EKi)

RG

7321(P

I3Ki)

RG

7422 (PI3K

/mTor)

RG

7440 (Akti)

Dulanerm

in

Bcl-2/A

BT-263

MD

M2

Antagonist

RG

7304/CK

I27

Hedgehog Inh

Anti-M

et/MetM

Ab

huMA

bG

lypican-31

Topoisomerase

I inh1

Breast cancer

Lung cancer

Colon cancer

Melanoma

Glioblastoma

Solid Tumors

Hematology

Halozyme

Pathway/MOA Angiogenesis HER2 HER1 B-Cell PI3K/Akt/MEK/BRAF Apo Other

Oncology: Setting the standard of careCombining products in our portfolio

1 Opt-in opportunity from Chugai

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Combining targeted therapies and changing medical practice

CLEOPATRA ph III1L mBC, HER2+Herceptin + pertuzumab

Ph Ib/IIHeavily pretreated mBC, HER2+T-DM1 + pertuzumab

MARIANNE phase III*1L mBC, HER2+T-DM1 + pertuzumab

Ph Ib2L mBC, HER2+PI3Ki (RG7321) + T-DM1

Ph IbSolid tumorsPI3Ki (RG7321)+MEKi (RG7420)

NeoSphere rand ph IIneo-adjuvant BC HER2+Herceptin + pertuzumab

AVEREL ph III1L mBC , HER2+Herceptin + Avastin

TrialIndicationCombination

*in preparation

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Transforming cancer care

In 2010, it is estimated that 250,000 patients will be treated with Avastin

New paradigm shift in cancer treatment: benefit with increased treatment duration

Providing access to the new treatment regimens (e.g. longer duration)

Strong portfolio with focus on personalized healthcare

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Jakob Dupont, M.D.Associate Group Medical Director, Genentech

Avastin: Phase III GOG-0218

Phase III trial of bevacizumab in the primary treatment of advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer: A Gynecologic Oncology Group (GOG) study

Robert A. Burger et al, ASCO 2010

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GOG-0218: Schema

Front-line: Epithelial OV, PP or FT cancer

• Stage III optimal (macroscopic)

• Stage III suboptimal

• Stage IV

n=1800 (planned)

Stratification variables:• GOG performance status (PS)• Stage/debulking status

1:1:1

15 months

Paclitaxel (P) 175 mg/m2

Carboplatin (C) AUC 6

Placebo

IArm

Cytotoxic(6 cycles)

Maintenance(16 cycles)

(CP)


Paclitaxel (P) 175 mg/m2

PlaceboBEV 15 mg/kg

II(CP + BEV)

BEV 15 mg/kg


Paclitaxel (P) 175 mg/m2III

(CP + BEV→ BEV)

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GOG-0218: Analysis Plan

• Primary analysis– Compare investigator-determined progression-free survival (PFS) for

each BEV arm vs control• If both results positive, compare Arm III (CP + BEV → BEV) vs

Arm II (CP + BEV)– Disease progression based on: RECIST, global clinical deterioration,

or CA-1251

– Planned sample size of 1800 based on:• 90% power to detect PFS hazard ratio (HR) ≤0.77

– Median PFS shift: 14.0 months → 18.2 months

• Secondary analyses: Overall survival (OS), safety, quality of life; correlative laboratory studies

1. Gynecologic Cancer Intergroup Criteria - Rustin et al. J Natl Cancer Inst 2004

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Adverse event (grade when limited), n (%)

Arm ICP

(n=601)

Arm IICP + BEV(n=607)

Arm IIICP + BEV → BEV

(n=608)GI eventsa (grade ≥2) 7 (1.2) 17 (2.8) 16 (2.6)

Hypertension (grade ≥2) 43 (7.2)b 100 (16.5)b 139 (22.9)b

Proteinuria (grade ≥3) 4 (0.7) 4 (0.7) 10 (1.6)

Pain (grade ≥2) 250 (41.7) 252 (41.5) 286 (47.1)

Neutropenia (grade ≥4) 347 (57.7) 384 (63.3) 385 (63.3)

Febrile neutropenia 21 (3.5) 30 (4.9) 26 (4.3)

Venous thromboembolic event 35 (5.8) 32 (5.3) 41 (6.7)

Arterial thromboembolic event 5 (0.8) 4 (0.7) 4 (0.7)

CNS bleeding 0 0 2 (0.3)

Non-CNS bleeding (grade ≥3) 5 (0.8) 8 (1.3) 13 (2.1)

RPLS 0 1 (0.2) 1 (0.2)

GOG-0218: Select Adverse EventsOnset between cycle 2 and 30 days after date of last treatment

RPLS = reversible posterior leukoencephalopathy syndromeaPerforation/fistula/necrosis/leak

bp<0.05

CP (Arm I)

Arm I CP

(n=625)

Patients with event, n (%) 423 (67.7)

Median PFS, months 10.3Stratified analysis HR (95% CI)One-sided p-value (log rank)

GOG-0218: Investigator-Assessed PFS

+ BEV (Arm II)

ap-value boundary = 0.0116

+ BEV → BEV maintenance (Arm III)Prop

ortio

n su

rviv

ing

prog

ress

ion

free

Months since randomization

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

00 12 24 36


(n=623)

360 (57.8)14.10.717

(0.625–0.824)<0.0001a

18


418 (66.9)11.20.908

(0.759–1.040)0.080a

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GOG-0218: Subgroup Analyses of PFSCP + BEV → BEV (Arm III) vs CP (Arm I)

Hazard ratio

Experimental arm (CP + BEV → BEV;

Arm III) betterControl arm

(CP; Arm I) better

Stage 3 optimal (n=434) 0.618

Stage 3 suboptimal (n=496) 0.763

Stage 4 (n=318) 0.698

PS 0 (n=616) 0.710

PS 1/2 (n=632) 0.690

Age <60 years (n=629) 0.680

Age 60–69 years (n=409) 0.763

Age ≥70 years (n=210) 0.678

Treatment hazard ratio

0.33 0.5 0.67 1.0 1.5 2.0 3.0

20GOG-0218: Ramification of Using CA-125 as Determinant of Progression

0.6450.717Hazard ratio

0.00010.0001p-value

Protocol-definedPFS analysis

CA-125-censoredPFS analysis

Regulatory analysis

Median PFS, months

CP (Arm I) 10.3 12.0

CP + BEV → BEV (Arm III) 14.1 18.0

Absolute difference in median PFS (months) 3.8 6.0

Censored for CA-125, %

CP (Arm I) 0 20

CP + BEV → BEV (Arm III) 0 29

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GOG-0218: Overall Survival (OS)

• Events observed in 24% of patients at time of data lock• After primary endpoint changed from OS to PFS

– Unblinding to treatment assignment allowed at time of disease progression

OutcomeArm I

CP(n=625)



(n=623)

Deaths, n (%) 156 (25.0)

150 (24.0)

138 (22.2)

1-year survival, % 90.6 90.4 91.3

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GOG-0218: Conclusions

• GOG-0218 met the primary objective in the front-line treatment of advanced ovarian (epithelial OV, PP and FT) cancer; PFS withCP + BEV → BEV maintenance (Arm III) statistically superior to CP alone (Arm I)– PFS with CP + BEV (Arm II) not statistically superior to CP (Arm I)

• Interpretation of survival analysis limited

• Treatment regimen generally well tolerated; adverse events (including GI perforation) similar to previous BEV studies

• BEV – first molecular targeted and first anti-angiogenic agent to demonstrate benefit in this population

• CP + BEV → BEV maintenance should be considered one standard option

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Avastin for advanced ovarian cancer should be considered one standard option*

• This is the first Phase III study of an anti-angiogenic medicine in advanced ovarian cancer to meet its primary endpoint.

• Another phase III trial of Avastin in front line ovarian cancer (ICON-7) will report in 2010.

• We plan to discuss these data with the FDA and other health authorities.

• Additionally, a second line platinum-sensitive Avastin phase III trial will report in 2011.

*Robert A. Burger et al, ASCO 2010

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Building on our understanding of Avastin’s potential

Stefan Frings, M.D.Avastin Franchise Director

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What’s important for Avastin at ASCO 2010?

• Avastin – a potential new standard of care in ovarian cancer

• Insights into optimal treatment duration

– Longer duration of Avastin therapy demonstrated to be more effective than shorter in ovarian cancer

– In mCRC, treatment beyond progression may yield superior OS

• Strong data solidifying Avastin’s essential role in our core indications

– ARIES in mCRC

– Meta-analysis in mBC

– ARIES in mNSCLC

• New phase III data on Avastin in gastric and prostate cancers

25

26

Results from ARIES observational cohort studyResults from ARIES observational cohort study

Pts alive 2 months after

1st PD (n=1026)

Pts alive 2 months after

1st PD (n=1026)

BBP (n=408)(BV and CT) < 2mo after PD

BBP (n=408)(BV and CT) < 2mo after PD

No BBP (n=336)(CT < 2mo after PD) and

(no BV after PD)

No BBP (n=336)(CT < 2mo after PD) and

(no BV after PD)

Other* (n=282)No treatment ever, BV and/or CT ≥ 2mo

after PD (not included in analysis)

Other* (n=282)No treatment ever, BV and/or CT ≥ 2mo

after PD (not included in analysis)

11

22

33

MDs choice of therapy

MDs choice of therapy

Objective: To evaluate the association between early exposure to Bevacizumab (Avastin) beyond 1st PD (BBP) and survival beyond 1st PD

27

Avastin treatment beyond progression may yield superior overall survival

t0= PD+2mos

Surv

ival

Bey

ond

Prog

ress

ion

No BBPBBP 7.5 14.1

Months

ARIESARIES

Cohn, et al. ASCO 2010, Abstract #3596 Grothey, A. et al. JCO, 2008

BRiTEBRiTE

9.2 16.8

Months

% S

urvi

val B

eyon

d Pr

ogre

ssio

n

2828

ARIES confirms BRiTE data

ARIES study

Median OS from initiation of 1st line therapy



BRiTE registry

Median OS from initiation of 1st line therapy



Multivariate Analysis of Pre- and Post-Treatment Variables on SBP

HR = 0.51 for BBP

(95% CI, 0.42 to 0.63)

Multivariate Analysis of Pre- and Post-Treatment Variables on SBP

HR = 0.52for BBP

(95% CI, 0.42 to 0.63)

2929

Avastin Treatment through Multiple Lines (TML)Phase III in Metastatic Colorectal Cancer – ML18147

Standardfirst-line

chemotherapy + Avastin Standard

second-line chemotherapy

+ Avastin

Standardsecond-line

chemotherapy

First-line Second-line

Progression

Primary endpoint = OSFPI Q1 2006 - enrolment completed June 2010

RANDOMISATION

(n=810)

3030

Summary of data on Treatment through Multiple Lines (TML)

• ARIES data strengthens the hypothesis generated by BRiTE that longer treatment duration with Avastin, i.e. treatment through multiple lines, may provide meaningful benefits for patients.

• We look forward to results from the prospective Phase III Avastin study in mCRC(ML18147) to further understand how duration of therapy impacts outcome for patients.

31

Avastin in HER2 negative metastatic breast cancer

• In three 1st and one 2nd line phase III mBC trials, irrespective of chemotherapy partner, Avastin has consistently

– met the primary objective of significantly prolonging PFS1–4

– demonstrated consistent benefit across all subgroups of patients1–5

– significantly increased ORR2,3,6

– shown a consistent and predictable safety profile2,3,7

311. Gray, et al. JCO 2009; 2. Robert, et al. ASCO 2009; 3. Miles, et al. JCO 2010; 4. Brufsky et al., SABCS 2009; 5. Dieras, et al. ECCO/ESMO 2009; 6. Klencke, et al. ASCO 2008; 7. Miles. EJC Suppl 2008

3232

BV=bevacizumab, PL=placebo, PFS=progression-free survival, ORR=objective response rate, OS=overall survival* Permitted continuing on BV or crossing over to BV† Analyses based on IRF assessments ‡ 15 mg/kg BV only

Comparison of the 1st line mBC studies

E2100 AVADO* RIBBON-1*No. of patients 722 736 1237Geography US (92%) Ex-US US (50%)

Randomization ratio (BV:PL) 1:1 1:1 2:1

Chemotherapy Paclitaxelweekly Docetaxel

Capecitabine,Docetaxel/nab-Paclitaxel,

Doxorubicin/Epirubicin

Primary Endpoint PFS† PFS‡ PFS

Key Secondary Endpoints OS, ORR OS, ORR,

1-yr survivalOS, ORR,

1-yr survival

J. O’Shaughnessy et al., ASCO 2010, abstract #1005

3333

Chemotherapy use in First-line HER2-negative Metastatic Breast Cancer

US Top 4 EU

*Single agent or combination treatment

14%17%

20%

15%

11%

23%

Paclitaxel Paclitaxel protein-boundDocetaxel Taxane DoubletsXeloda Other/Anthracycline

27%

16% 16%

8%

33%

Paclitaxel* Docetaxel*Anthracycline XelodaOther

3434

Overview of Efficacy Results from the Individual Studies in the Pooled Analysis

E2100 AVADO* RIBBON-1 (Cape)RIBBON-1

(Tax/Anthra)Non-BV BV Non-

BV BV Non-BV BV Non-BV BV

Median PFS, mo 5.8 11.3 8.0 8.8 5.7 8.6 8.0 9.2

StratifiedHR (95% CI)

0.48(0.39–0.61)

0.61(0.48–0.68)

0.69(0.56–0.84)

0.64(0.52–0.80)

p-values p<0.0001 p=0.0003 p=0.0002 p<0.0001

BV=bevacizumab, Cape=capecitabine, Tax/Anthra=taxane/anthracycline* 15 mg/kg cohort

• The safety profile of BV was consistent across Phase III MBC trials.


35

Results of Meta-analysis of Phase III Studies: Progression-Free and Overall Survival


Non-BV(n=1008)

BV(n=1439)

Median, mo 26.4 26.7

HR (95% CI) 0.97 (0.86–1.08)

1-yr survival rate (%) 77 82

Non-BV(n=1008)

BV(n=1439)

Median, mo 6.7 9.2

HR (95% CI) 0.64 (0.57–0.71)

Progression-free survival Overall survival

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Considerations on PFS and OS in mBC trials

• Advanced breast cancer is an incurable disease; lengthening the time women live without the cancer worsening is clinically meaningful by sparing patients…

– for as long as possible from symptoms of progressive breast cancer

– toxic effects of subsequent therapies

– the psychological burden and uncertainty that comes with progression

• Avastin has demonstrated clinically meaningful PFS benefit but no significant OS improvement across 3 first-line HER2-neg mBC studies & in pooled analysis Of note,

– The objective of the trials was to demonstrate superior PFS

– OS outcome may have been confounded by• Uncontrolled use of further lines of anti-cancer therapies• Cross-over with Avastin to control-arm patients

– There is a greater chance of affecting OS in populations with shorter PPS

36Broglio and Berry. 2009. J Natl Cancer Inst. 101:1642-49; Saad, Katz, and Buyse. 2010. J Clin Oncol. 28:1958-62; Burzykowski, et al. J Clin Oncol. 26:1987-92; Miller. 2008. NEJM. 358: 1637-1638

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Avastin phase III trials in gastric and prostate cancer

37

AVAGAST: A Randomized Double-Blind Placebo- Controlled Phase III Study

Starting dose of bev/placebo: 30 minutes, subsequent doses: 15 minutes

Capecitabine*/Cisplatin (XP)

+ Placebo q3w

Capecitabine*/Cisplatin (XP)

+ Bevacizumab q3w

Locally advancedor metastatic gastric cancer

R

Primary endpoint: OS

Secondary: PFS, TTP, ORR, duration of response, safety, QoL, biomarkers

39

AVAGAST: Efficacy results

Kang et al., ASCO 2010, LBA4007

XPn=387

XP + Avastin(n=387)

Median OS, mo 10.1 12.1

HR 0.87

P-value 0.1002

XPn=387

XP + Avastin(n=387)

Response rate (%) 29.5 38.0

P-value 0.0121

Median PFS, mo 5.3 6.7

HR 0.80

p-value 0.0037

40

AVAGAST: Regional Differences in Efficacy

Overall survival

Hazard ratio

Asia Europe Pan-America

20

18

16

14

12

10

8

6

4

2

0

1.0

0.8

0.6

0.4

0.2

0.0

XP + Placebo XP + Avastin

0.97

0.85

0.63

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AVAGAST: Safety Events

Number of patients (%)XP + Placebo

N=381XP + Bev

N=386

Hypertension 0.5 6.2

Hemorrhage 3.9 3.9

Wound-healing complications 0.0 0.5

GI-perforations 0.3 2.3

ATE 2.1 1.3

VTE 9.4 6.4

60-day mortality rate 5.8 3.1Kang et al., ASCO 2010, LBA4007

42

AVAGAST Summary & Conclusions

• Primary endpoint of OS not met

• Secondary efficacy endpoints (PFS, best ORR) significantly improved, indicating clinical activity of Avastin + chemo in AGC

• Heterogeneous efficacy results in both treatment arms across geographic regions

Hypothesis generating with regard to tumor burden, patient status, practice patterns, genetics?

• No unexpected / new safety signals for Avastin

• Further analysis ongoing, including preplanned biomarker analysis

43

Hormone-resistant prostate cancer study CALGB 90410: Treatment Schema

RA

ND

OM

IZE

(1:1

)R

AN

DO

MIZ

E (1

:1)

Arm 2Dexamethasone 8 mg po x 3 doses Docetaxel 75 mg/m2 on day 1 q 21 daysPrednisone 10 mg po dailyPlacebo1 IV on day 1 q 21 days

Arm 1Dexamethasone 8 mg po x 3 dosesDocetaxel 75 mg/m2 on day 1 q 21 daysPrednisone 10 mg po dailyBevacizumab1 15 mg/kg IV on day 1 q 21 days

•ASA 325 mg encouraged in all patients that can tolerate 1In the event of intolerable toxicity to Docetaxel the Bevacizumab\placebo may be continued alone until POD

Primary endpoint: Overall Survival (OS)

Secondary endpoint:

50% decline in PSA1

Progression Free Survival (PFS)1

Toxicity

44

0 6 12 18 24 30 36 42Time(months)

0.0

0.2

0.4

0.6

0.8

1.0

Ove

rall

Surv

ival

(pro

babi

lity)

Placebo+DoceBev+Doce, log-rank p=0.181

Kaplan-Meier Overall Survival Curves by Treatment Arm

526 480 390 305 199 100 44 22524 484 417 327 217 117 52 23

Placebo+DoceBev+Doce

Number of Patients at Risk

Median DP = 21.5 (20.0-23.0)Median DPB=22.6 (21.1-24.5) HR= 0.91 (0.78-1.05)

45

0 6 12 18 24 30 36 42Time(months)

0.0

0.2

0.4

0.6

0.8

1.0

PFS

(pro

babi

lity)

Placebo+DoceBev+Doce, log-rank p<0.0001

Kaplan-Meier PFS Curves by Treatment Arm

526 303 134 75 34 8 4 0524 381 194 97 44 15 5 1

Placebo+DoceBev+Doce

Number of Patients at Risk

Median DP = 7.5 (6.7-8.0)Median DPB=9.9 (9.1-10.6) HR= 0.77 (0.68-0.88)

46

Secondary Endpoints: Objective Response and 50% Decline in PSA

Clinical Endpoint

Arm 1DP+B

(N=524)

Arm 2 DP

(N=526)

p-value

≥50% decline in PSA(95% CI)

69.5% (65.2-73.5)

57.9% (53.3-62.3)

0.0002

Objective Response(95% CI) (# with measurable disease)

53.2%(46.8-59.6)

(248)

42.1% (36.2-48.2)

(273)

0.0113

47

Conclusions• The addition of bevacizumab to DP showed a non-significant

trend in OS in men with mCRPC– 21.5 mo. vs 22.6 mo., p=0.181 (HR = 0.91)

• The addition of bevacizumab to DP compared to DP in metastatic CRPC resulted in a significantly greater

– PFS 9.9 mo. vs. 7.5 mo., p < 0.0001 – objective response rate 53.2% vs. 42.1% , p= 0.0113– PSA decline in PSA 69.5% vs. 57.9%, p= 0.0002

48

Conclusions

• Differences in primary and secondary endpoints may be related to:

– Underpowered Study: OS in the control arm of 21.5 months exceeds the 19.2 month OS reported in the TAX327 trial (Berthold et al. JCO 2008;26:242-45)

• Stage migration• Reflection of good risk population (47%)

– Impact of subsequent therapy on OS

– Discordance between OS and PFS\overall response

• Exploratory analyses which subgroups obtain potential clinical benefit are ongoing

49

Gastric and prostate cancer conclusions

• Based on current data sets there will be no regulatory filings for gastric and prostate cancer.

• We will determine next steps particularly for gastric cancer.

5050

Avastin takeaways ASCO 2010 Continuing advance our understanding of Avastin’s potential

• Avastin – a potential new standard of care in ovarian cancer

• Patients benefit from longer Avastin treatment

• Strong data solidifying Avastin’s essential role in our core indications

• Avastin has activity in gastric and prostate cancer

51

Prof. Gilles Salles, M.D., Ph.D.Principal Investigator of PRIMA studyHospices Civils de Lyon, France

Rituximab: PRIMA study

Rituximab Maintenance for 2-Years in Patients with Untreated High Tumor Burden Follicular Lymphoma After Response to Immunochemotherapy

G. A. Salles, J. F. Seymour, P. Feugier, F. Offner, A. Lopez-Guillermo, R. Bouabdallah, L. M. Pedersen, P. Brice, D. Belada, L. Xerrion behalf of PRIMA investigators

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Rationale for the PRIMA study• Follicular lymphoma: the second most common lymphoma subtype

• Usually remains incurable despite efficient therapy (rituximab + chemotherapy) providing disease control for variable time periods

• Median life expectancy is 12–15 years; patients may suffer from several recurrences of their lymphoma

• Length of remission decreases at each treatment recurrence

• Rituximab is an anti-CD20 monoclonal antibody that has been shown to improve outcome for follicular lymphoma patients when used in combination with chemotherapy

• Previous studies suggested that rituximab maintenance may benefit patients with relapsed or previously untreated follicular lymphoma

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PRIMA: primary objective and design

• To assess whether 2-year maintenance treatment with rituximabafter induction immunochemotherapy is able to improve the progression-free survival (PFS) of untreated follicular lymphoma patients in need of first-line therapy

A study coordinated by the

No responseoff study

Maintenance12 x rituximab(q2mo for 24 mo)

Observation

Untreated follicular NHL

High tumor burden

Induction8 x rituximab

Chemotherapy(6 x CHOP or 8 x CVP or

6 x FCM)

RESPONSE1217 patients

1018 patients

54

• Rituximab maintenance significantly reduced the risk of lymphoma progression by 50% (HR=0.50, 95% CI 0.39; 0.64)

HR=0.50p<0.0001

Time (months)

Rituximab maintenanceN=505

ObservationN=513

60 12 18 24 30 36

Prog

ress

ion-

free

rate 0.8

0.6

0.4

0.2

0

1.082%

66%

Patients at risk505513

472 443 336 230 103 18469 411 289 195 82 15

Primary endpoint (PFS) met at the planned interim analysis

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Secondary endpoints: consistent results

624394216370431

76822228

721290

0.450.590.380.390.61

0.430.690.51

0.520.45

0.33, 0.620.39, 0.900.19, 0.770.25, 0.610.43, 0.87

0.31, 0.590.44, 1.080.13, 2.07

0.38, 0.700.29, 0.72

Subgroup

<60≥60

FLIPl=2FLIPl≤1

FLIPl≥3

R-CHOPR-CVPR-FCM

CR/CRuPR

0 1 2

Hazard ratio

Response to induction

Induction chemotherapy

FLIPl index

Age

Category 95% CIsHazard

ratioN

• Rituximab maintenance decreased the risk of starting a newanti-lymphoma treatment by 39% (HR=0.61, p<.0003)

Favors maintenance Favors observation

• Rituximab benefit (PFS) in patient subgroups

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Conclusions • Current results do not allow to evaluate a possible effect on overall survival

– Additional follow-up will provide this information

• The effect of rituximab maintenance in first line appears superior to that previously described in relapsing patients:

– after R-CHOP in the EORTC study* HR = 0.69– after R-CHOP in PRIMA HR = 0.43

• Safety was consistent with the known profile of rituximab with no new or unexpected safety signals during or after maintenance treatment

• These results are likely to define a new standard of care for FL patients in need for treatment

• Rituximab maintenance for 2 years constitutes a new platform to further develop more efficient (and well tolerated) strategies

* van Oers et al. ; J. Clin. Oncol, 2010

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Setting the standard of care in oncologySummary and Q&A

K. Mahler, Head of Investor Relations, Roche

58

107

77

5845 51 50 47

29

113 5 1

25

9

10

1511 8 10

9

9

26 4 6 4

22

2 21

3

1

11

1 2

1

0

20

40

60

80

100

120

140

160 PlenaryClinical Science SymposiumOralPoster DiscussionPoster

n=66n=67n=71

n=86

n=143

n=65 n=63

n=41

n=13n=5 n=5 n=3 n=2

n=1

No.

of A

bstr

acts

ASCO 2010: News flow and clinical benefit driving standard of care

Avastin

Herceptin

Nexavar

Tarceva

XelodaErbitu

xSutent

Rituxan

Panitumumab

T-DM1

Recentin

AZD2281BSI-2

01

Pertuzumab

5959

Major clinical data newsflow for our late-stage oncology NMEs in 2010-2011

Hedgehog Pathway InhibitorPh II advanced Basal Cell Carcinoma

Hedgehog Pathway InhibitorPh II met. Ovarian cancer

RG7204 (BRAF inh.)Ph II 2nd/3rd line met. Melanoma

RG7204 (BRAF inh.)Ph III 1st line met. Melanoma

Pertuzumab+HerceptinPh II Neoadjuvant BC

NEOSPHERE

T-DM1 vs:Herceptin+docetaxel

Ph II 1st line met. BC

Pertuzumab+HerceptinPh III 1st line met. BC

CLEOPATRA

= pivotal data

2010 2011

Hedgehog Pathway InhibitorPh II 1st line met. Colorectal cancer

= proof of concept data

RG7159/GA101Ph II H2H vs. Rituxan, iNHL

60

Back-up slides

61

Incidence of ovarian cancerAvastin: First clinical breakthrough in over a decade

Major-market ovarian cancer incidence cases, 2008-2018

Inci

dent

cas

es

15'750 16'620 17'420

4'280 4'550 4'820

25'860 27'580 29'350

11'75012'640

13'620

0

10'000

20'000

30'000

40'000

50'000

60'000

70'000

80'000

2008 2013 2018

Stage IV

Stage III

Stage II

Stage I

Decision Resources, May 2010

62

Rituxan growth opportunitiesAddressing unmet medical needs

0

10

20

30

40

50

60

70

iNHL

iNHLmaint

aNHLCLL

iNHL

iNHLmaint

aNHLCLL

iNHL

iNHLmaint

aNHLCLL

U.S. Top-5 EU E7

Growth opportunities

Thou

sand

pat

ient

s tr

eate

d No MabThera/Rituxan

MabThera/Rituxan

E7: Brazil, Russia, China, Mexico, Turkey, South Korea, India

63

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