clinical development in asia pacific and japan rolf schuermann, m.d., ph.d., vice-president,...

Bayer Schering Pharma

Clinical Development in Asia Pacific and Japan

Dr. Rolf Schürmann GTCBio , Seattle, Jan 2010

Dr. Rolf Schürmann

Vice-President,

Head of Global Clinical Development Women’s Healthcare

Bayer Schering Pharma AG

Dr. Rolf Schürmann GTCBio , Seattle, Jan 2010 •

Agenda

Examples

Global R&D Environment

Benefits of R&D in Asia Pacific and Japan

Outlook


Current Global R&D Environment

Global competition

Rising costs of development

Decreasing productivity of R&D

An industry under pressure

Post Cox-2 environment

Public disclosure

Limited pool of trained investigators for clinical trials


“Within three years, up to 65% of

FDA-regulated clinical trials for the top

pharmaceutical companies

will be conducted outside of U.S…”

Tufts Outlook 2008 Report, January 2008


Agenda

Examples



Outlook


Off-shoring Clinical Development

Sponsor perspective:

Access to large number of patients, access to treatment naive patients

Potential of emerging markets

Economic advantage

Health authority perspective:

Drive to promote domestic biotechnology and medical research

International agreements easing FDA/EMEA acceptance

But: Acceptability of foreign data?

Investigator perspective:

Personal scientific interest and development of staff

Financial incentives

Source: FDA, Visiongain, McKinsey


How to optimize global patient recruitment- Shifting Global Patient Recruitment -

Phase III trials in November 2007

30% of clinical trials conducted

outside of US (157 of 509)

More than 50% of study sites

outside of US (13,521 of 24,206)

From 1995 to 2005, the number of countries

serving as trial sites outside

the US more than doubled

Ethical and Scientific Implications of the Globalization of Clinical

Research S Glickman et al. NEJM 360;8

Dr. Rolf Schürmann GTCBio , Seattle, Jan 2010 • Page 10

Lead time to start a study in Asian countries

Country CTA review time Special requirements for

CTA

China* 9 – 12 months Full Dossier (TRDs + clinical and

non clinical reports) required for

CTA.

Japan CTN 30 days CT Notification form + study

protocol, IC and CRF

Korea Ca. 2 months Technical documentation and

study protocol

Taiwan 2- 3 months Technical documentation and

study protocol

EU / US CTA / IND 30 days

Multinational studies

60 days

Technical documentation and

study protocol

2 4 6 8 10 12 Months

Draft protocol can be accepted to

start CTA review.

* Data from Hong Kong where review is approx 3 months long can be used only if CTA is approved by SFDA.


Japan – South Korea – ChinaIncreasing communications among regulators

2007 April in Seoul

2008 April in Tokyo

http://www2.convention.co.jp/eaprs2008ph/en/purpose/

http://www2.convention.co.jp/eaprs2008ph/en/purpose/


Agenda

Examples



Outlook


Nexavar is the First Drug to Demonstrate Overall Survival Benefit in HCC

Nexavar bears the potential to become the new standard

of care in patients with unresectable liver cancer

Sorafenib vs placebo: *P=0.0006; †P=0.000007

Hazard ratio Sorafenib Placebo

Median overall survival (44% improvement)* 0.69 46.3 weeks 34.4 weeks

Median time to progression (73% prolongation)† 0.58 24.0 weeks 12.3 weeks

Time to ProgressionOverall Survival


Liver Cancer (HCC): Representing a Significant Therapeutic Opportunity

U.S.

15,000

E.U.

54,000China

346,000 Japan

40,000

Globally more than 620,000 new cases of HCC annually

Annual cases of HCC Unprecedented results for

Nexavar in HCC – improvement

of overall survival by 44%

Approved for treatment of HCC

e.g. in Europe, USA, Canada,

Korea, India, China, Japan

Additional studies in HCC

ongoing (combination, post-

TACE, adjuvant setting)

No near-term major competitors

anticipated

Source: Globcan 2002


Nexavar: Overall Survival in Asia-Pacific HCC Study

Su

rviv

al

Pro

bab

ilit

y

SorafenibMedian: 6.5 months (95% CI: 5.6-7.6)

PlaceboMedian: 4.2 months (95% CI: 3.7-5.5)

HR (S/P): 0.68 95% CI: 0.50-0.93P=0.014

0.25

0.50

0.75

1.00

0

0

Months

2 4 8 10 12 14 16 20 22

76 62 41 26 23 15 9 5 4 1 0 0

Patients at Risk

Placebo

6 18

Adapted from Cheng A et al. Presented at ASCO Annual Meeting; May 30-June 3, 2008; Chicago, IL.


Nexavar: Comparison of Efficacy Between the Asia-Pacific and SHARP Trials

End point

Asia-Pacific2 SHARP1

Hazard Ratio

(95% CI) P-value

Hazard Ratio

(95% CI) P-value

OS0.68

0.0140.69

<0.001(0.50-0.93) (0.55-0.87)

TTSP0.90

0.4981.08

0.768(0.67-1.22) (0.88-1.31)

TTP0.57

<0.0010.58

<0.001(0.42-0.79) (0.45-0.74)

PFS0.62

<0.0010.65

<0.001(0.46-0.82) (0.52-0.79)

1. Llovet JM et al. NEJM, 2008.

2 Adapted from Cheng A et al. Presented at ASCO Annual Meeting; May 30-June 3, 2008; Chicago, IL.

Patients on drug from SHARP trail experienced a 44% OS benefit

Patients on drug from AP trail experienced a 47% OS benefit


Xarelto: #1 patient enrolment globally and the high recruitment rate saved 2 months to end the trial

0

2

4

6

8

10

12

14

Recruitment duration % of Total patients

BSP International Hemato/cardio Clinical trail (2006/2007)


Australia11213

11714

11223

KoreaDragon

Hong KongDragon

HCC 11546

New Zealand11213

11714

ChinaDragon

11608 Fxa

11609 Fxa

11708 Fxa

AP regional and Global Trials recruiting


ChinaGadovist 91682

Primovist Patent-1

Patent-2 Chest 1

Chest 2 Einstein

Einstein ext Magellan

r-th. Gastric

Storm Nexus

ACE Maestral

13085 Alemb.

VEGF YAZ 1

Q OC Qlaira

YAZ YAZ 2

LCS 12917

Australia91681 91749

91783 91784

Patent-1 Patent-2

Chest 1 Chest 2

Einstein Einstein ext

Magellan Storm

Step Maestral

Potent Beyond F-up

CARE 1 CARE 2

View-2 FC

12917 Q libido

Q tolerability

IndonesiaEinstein

Einstein ext

Magellan

Maestral

Hong KongEinstein

Einstein ext

Magellan

Storm

ACE

Maestral

YAZ

12007

PakistanMagellan

Maestral

TaiwanPatent-1

Patent-2

Chest 1

Chest 2

Einstein

Einstein ext

Magellan

Storm

Step

12917

PhilippinesEinstein

Einstein ext

Maestral

SingaporePatent-1

Einstein

Einstein ext

Magellan

Storm

NSCLC

Zeal

13085

View-2

12917

MalaysiaEinstein

Einstein ext

Magellan

ThailandEinstein

Einstein ext

Magellan

Zeal

Maestral

Q libido

Q tolerability

India91681

Einstein

Einstein ext

Magellan

View-2

New ZealandChest 1

Chest 2

Einstein

Einstein ext

Magellan

Storm

Step

12917

Korea91682

Patent-1

Patent-2

Chest 1

Chest 2

Einstein

Einstein ext

Magellan

Gastric

Post Tace

Storm

NSCLC

Zeal

View-2

LCS

12007

12917

On-going AP Trials Ph I to III


Shorter development time for Bayer’s

development assets.

Earlier access to the Japanese market.

No drug lag in Japan.

More development projects within the

same resource frame.

Increased probability of regulatory

success.

Global trials

(incl. Japan)

Domestic

programs

Pan-Asian

trials

(incl. JP)

Japan: Most of the Phase III are Global Trials Involving Japanese Centers


NEXAVAR

CRC

NEXAVAR

Breast cancer

NEXAVAR

GC 1st line Cape

NEXAVAR

Thyroid cancer

L19-SIP

Cancer

L19-TNF alpha

Cancer

VEGF Trap

AMD

XARELTO

Stroke Px aFib

XARELTO

VTE Px Medically ill

XARELTO

VTE Px Abdo. surgeries

Preclinical or Pending Decision

Japan Development Portfolio by BUs (Sep. 2009)

Phase I Phase II Phase III Under Review Approval in 2009

GLUCOBAY

ODT

CIPRO IV

(PAA)

XARELTO

VTE Px OS

XARELTO

VTE Treatment

Cinaciguat

Acute HF

Riociguat

Pulmonary HT

XARELTO

ACS

CIPRO Inhale

COPD

ADAPTINOL

LCM

[18F]FEDAA 1106 PET

[18F]Glutamic acid PET

[18F]DPA-714 PET

[18F]SIGMA-2 PETBAY 94-9172 PET

Alzheimer (P-III)

GADOVIST

Brain Met

IOPAMIRON

Plastic PFC (AS)

GADOVIST

Whole Body

GADOVIST

CNS

KOGENATE-PF

Hemophilia

VEGF Trap

CRVO

KOGENATE-FS

2000 IU (PAAs)

BETAFERON

(PAAs)

NEXAVAR

GC 1st line S1

DAST

Cancer

NEXAVAR

Ovarian cancer

NEXAVAR

Post-TACE HCC

NEXAVAR

NSCLC 3rd/4th line

NEXAVAR

Adjuvant HCC

FLUDARA iv

NHL

FLUDARA oral

B-CLL

CAMPATH

GVHD (ISS)

SEGRA Topical

Atopic dermatitis

BAY 60-4552 sGC

NEXAVAR

Unresectable HCC

NEXAVAR

GC 2nd line paclitaxel

ADALAT

FDC

YAZ

Dysmenorrhea

GME DGI ONC STH WHC

S-PR Antagonist

Fibroids

ER Agonist

Vasomotor symptom

E2+DRSP

Contraception

DRSP Successor

Contraception

LIPOXIN

Gastroenterology

VEGF Trap

DME

VEGF Trap

Myopic CNV AP/J

BAY VII

Hemophilia

KOGENATE liposome

Hemophilia

Riociguat

Pulmonary CTEPH

Amikacin inhale

VAP

ADALAT

HD

FOSRENOL LCM

Sachet

FOSRENOL LCM

Pre-dialysis

MIRENA

(PAA)

BAY 94-9172 PET

Alzheimer (P-II)

Riociguat

PH-LVD

ADALAT CR

40 mg Small

NEXAVAR

Thyroid

Intendis


Agenda

Examples



Outlook


GD Asia Facility Opening


Summary and Outlook

The trend for off-shoring of clinical research into the

Asia-Pacific region will continue

The are limits in how far regional externalization of

R&D is possible (ethnicity, global acceptance)

Bayer Schering Pharma will continue to significantly

invest global R&D resources into the AP region


Thank you for your kind attention

Your questions?

clinical development in asia pacific and japan rolf schuermann, m.d., ph.d., vice-president,...

Documents

rolf schrmann gtcbio

asia pacific

asiapacific hcc study1

overall survival time

clinical reports

study protocol taiwan

overall survival benefit

weeks median time