C-1 Xinlay™ (atrasentan) Oncologic Drugs Advisory Committee September 13, 2005.

C-1

Xinlay™ (atrasentan)

Oncologic Drugs Advisory Committee

September 13, 2005

C-2

Atrasentan

A potent selective ETA receptor antagonist

Orally bioavailable

Once-daily dosing Half-life (t½) = 25 hours

O

O

OMeCO2H

Bu2N

N · HCl

O

C-3

Prostate Cancer Second Most Common Cancer in Men in the United States

>230,000 new cases of prostate cancer in 2005– 30,000 men will die of prostate cancer– Most have advanced metastatic HRPC– 85% have osteoblastic bone metastases– 90% require opiates in the last month of life

Limited treatment options currently approved– Docetaxel is the standard of care for metastatic

HRPC– Not all patients receive or are eligible

C-4

Proposed Indication

Xinlay™ (atrasentan) is indicated for the treatment of men with hormone refractory prostate cancer with metastases to bone

O

O

OMeCO2H

Bu2N

N · HCl

O

C-5

Atrasentan Development Program Initiated 1996

Other PCa(Ongoing)

Phase 1 Investigator-sponsored IND studies

Phase 1/2Unique

populations

M+ HRPC(N = 1228)

Phase 2/3 Double-blind,

placebo-controlled(N = 2484)

Atrasentan Clinical Trials

TTP EndpointM96-594 (N = 288)M00-211 (N = 809)

Non-TTPM96-500(N = 131)

C-6

Statistical Considerations

Studies M96-594 and M00-211 did not meet their primary endpoint – Study M00-211 IDMC recommended study stop for futility

Analysis of patients with bone metastases not protocol-specified

C-7

Analyses of Patients With Bone Metastases

Consistent benefit in patients with bone metastases– Delays disease progression, attenuates biomarkers, and slows

deterioration in quality of life – Across multiple measures in 2 studies

Strong scientific rationale based on emerging data – Role of the ET axis in PCa-osteoblast interaction

Study M00-211 is a large, placebo-controlled study – 690 of 809 (85%) patients have bone metastases

Large unmet need– 85% of patients with metastatic HRPC have bone metastases

C-8

Agenda

Unmet Need andMechanistic Rationale

Joel B. Nelson, MDChairman of UrologyUniversity of Pittsburgh

Efficacy Darryl J. Sleep, MD, FCSOncology Global Project HeadAbbott Laboratories

Safety Gary Gordon, MDOncology Vice PresidentAbbott Laboratories

Place in Therapy Michael A. Carducci, MDAssociate Professor in Oncology and Urology Johns Hopkins University

C-9

Consultants David Cella, PhD; Professor of Psychology and Behavioral

Science, Northwestern University

David Dearnaley, MD, FRCP, FRCR; Professor of UroOncology and Head of Urology, Royal Marsden Hospital and Institute of Cancer Research, London UK

Scott Emerson, MD, PhD; Professor of Biostatistics, University of Washington

Roberto M. Lang, MD; Professor of Medicine/Cardiologist, University of Chicago Hospitals

Daniel P. Petrylak, MD; Associate Professor of Medicine, Division of Hematology and Medical Oncology, Columbia University

C-10

Unmet Need and Mechanistic Rationale

Joel B. Nelson, MD

Chairman of UrologyUniversity of Pittsburgh

C-11

Treated with chemotherapyb (47%)

Not treated with chemotherapyb (53%)--------------------------------

• Side effects/toxicity• No perceived benefit• Quality of life

a 5-year prevalence: SEER 2005, NODB 2005b Source: Oncology, Inc. Onco Track MAT June 2005

617,000a

LocalizedPCa

232,090 New cases

in 2005

383,000a

AdvancedPCa

30,000Deathsin 2005

Incidence and Prevalence of Prostate Cancer

48,000a

Hormonerefractory

C-12

Metastatic HRPC Is Predominantly a Disease in Bone

Bone is a common metastatic site– Occurs in over 85% of men – Classically osteoblastic

Intractable bone pain

– Affects over 75% of patients

– Leads to major declines in QOL

– Main reason for hospitalization

– 90% require opiates in month before death

Skeletal-related events

– Pathological fractures

– Spinal cord compression

C-13

Treatment Remains Palliative

Reduction in SRE– Zoledronic acid

38% ZA vs 49% placebo

Palliation of morbidity– Opiate analgesics– Focal radiation therapy– Radiopharmaceuticals– Mitoxantrone and prednisone

C-14

Characteristics of Current Therapies Intravenous

Toxicity

Inevitable failure

Clear need for more treatment options

Mitoxantrone Docetaxel

Adverse Event Any Grade % Any Grade %

CHF 2

MI/Ischemia 5

Decreased LVEF 5 – 22 9.6

Dyspnea 8.7 – 15 15

Gastrointestinal 26 – 61 17 – 41

Neutropenia 32 – 79 41

C-15

Endothelins Act Via 2 Receptors

ET-1

ETB

VasoconstrictionMitogenesisAntiapoptosisOsteoblastic responsePain

Nelson et al. Nat Rev Cancer. 2003;3:110.

ET-2 ET-3

ETA

C-16

Rationale for Targeting ET Axis in Prostate Cancer

ET-1 is expressed in all stages of the disease

ET-1 clearance is decreased in HRPC

Osteoblasts express ETA at high density

– 105 106 receptors per cell

ET-1/ETA activation induces an osteoblastic response

Interruption of ET axis by atrasentan inhibits bone formation in preclinical models

C-17

Prostate Cancer – Bone InteractionA Vicious Cycle

Osteoblastic factors (ET-1)

Bone-derivedgrowthfactors

New bone

Prostate cancer cells

OsteoclastsMineralized bone matrix

Osteoblasts

Osteolyticfactors

ETA

C-18

Atrasentan Inhibits Osteoblastic Metastases in a Mouse Model

Yin et al. PNAS. 2003;100:10954-10959.

Control

New Bone

Cancer

Vehicle Atrasentan

Vehicle 2 mg/kg 20 mg/kg0

1

2

3

4

* *

Tumor area mm2/bone

*P < .05; **P < .01

mm2/boneNew bone area

Vehicle 2 mg/kg 20 mg/kg

**

0.0

0.5

1.0

1.5

**

Control

Atrasentan 2 mg/kgAtrasentan 20 mg/kg

C-19

Atrasentan Blocks Prostate Cancer-Induced Osteoblastic Response in Bone

Mohammad K, et al. Skeletal Complications of Malignancy NIH 2005.

Vehicle Atrasentan

Zoledronic acid Atrasentan + zoledronic acid

0

1.0×107

2.0×107

3.0×107

4.0×107

5.0×107

6.0×107

7.0×107

Histomorphometric analysis of intra-tibial LuCaP 23.1 tumor area

Vehicle

Atrasentan

Zoledronic acid

Atrasentan + zoledronic acid

m2

**

*P < .01

C-20

1995 1996 1997 1998 1999 2000 2001 2002 2003

ET Axis and Atrasentan Clinical Development Growing Focus on Bone Microenvironment

Phase 1 Atrasentan

studies begin

M00-211First dose

M96-594 First dose

Role of ET-1 in PCa• ? HRPC growth• ? Inhibits apoptosis• ? Osteoblastic• ? Pain

Atrasentan inhibits ET-1induced

bone formation in osteoblastic tumor model

ET-1/ETA axis causal in osteoblastic

bone metastases

M00-211 Last dose

Convergence ofclinical and

basic science

June 1996 Feb 1998 June 2001 Mar 2003

C-21


Efficacy

Darryl J. Sleep, MD, FCS

Oncology Global Project HeadAbbott Laboratories

C-22

Atrasentan Randomized Controlled TrialsMetastatic Hormone Refractory Prostate Cancer

Atrasentan 10 mg

Placebo

Atrasentan 2.5 mgM96-594

Randomization Disease progressionor study close

Open-label atrasentanextension

Screening

M00-211

Atrasentan 10 mg

Placebo

C-23

Dose-Ranging Study M96-594

288 patients with asymptomatic metastatic HRPC

Primary endpoint: time to disease progression– Clinical

– Radiographic

Open-label atrasentan extension

Atrasentan 10 mg (n = 89)

Placebo (n = 104)

Atrasentan 2.5 mg (n = 95)Screening


C-24

Time to Disease Progression Study M96-594 – ITT

0.0

0.2

0.4

0.6

0.8

1.0

0 90 180 270 360

Time from randomization (days)

Pro

bab

ilit

y o

f n

ot

pro

gre

ssin

g


Atrasentan 2.5 mg (n = 95)

Placebo (n = 104)

10 mg vs placeboP = .132HR = 0.769 (95% CI = 0.545, 1.085)

C-25

Change From Baseline to Final BAP and PSAStudy M96-594 – ITT

0

40

80

120

160

Final

Med

ian

ch

ang

e fr

om

bas

elin

e, n

g/m

L PlaceboAtrasentan 2.5 mg

Atrasentan 10 mg

0

10

20

30

40

50

Final

Me

an

ch

an

ge

fro

m b

as

elin

e, n

g/m

L +

SE Placebo

Atrasentan 2.5 mgAtrasentan 10 mg

BAP

**P < .01 compared with placebo

**

PSA

Time from randomization (week)

C-26

Study M00-211

809 patients with metastatic HRPC Major entry criteria

– Confirmed radiographic evidence of metastases Independent radiologic review of all baseline scans

– Confirmed medically or surgically castrate for ≥ 3 months

– Rising PSA or PSA ≥ 20 ng/mL

– No PCa-related pain requiring opiates

– Chemotherapy-naïve

– No prior or ongoing bisphosphonate therapy



Placebo (n = 401)

Open-label atrasentan extension

Screening

C-27

Baseline Characteristics BalancedStudy M00-211 – ITT

Median (range)

Placebo n = 401

Atrasentan 10 mg n = 408

Age, y 72 (45 – 92)

73 (45 – 93)

Weight, kg 83 (47 – 154)

81(54 – 177)

Hgb, g/dL 13 (9 – 18)

13 (9 – 17)

PSA, ng/mL 80(2 – 5425)

70(2 – 5784)

BAP, ng/mL 25(2 – 1599)

26 (2 – 1904)

Total ALP, IU/L 112 (41 – 3774)

110 (36 – 5482)

LDH, IU/L 188 (108 – 2365)

186 (97 – 1318)

Karnofsky score ≥ 90, % 87 88

C-28Primary Endpoint Time to Disease ProgressionStudy M00-211

Time to first Radiographic event

– Progression by 2 new lesions on bone scan

– Progression of extraskeletal metastases by modified RECIST criteria

Clinical event– Prostate cancer-related pain treated with

Any IV/IM/SQ opiates

Oral opiates or glucocorticoids for 10 of 14 consecutive days

Chemotherapy, radiotherapy

– Skeletal-related event

Spinal cord compression

Pathological fracture

– PCa progression event requiring intervention

C-29

Endpoint Assessment and Confirmation

Scans scheduled every 12 weeks

– Bone scans for all patients

– CT or MRI for patients with baseline extraskeletal metastases

– Unscheduled scans as clinically indicated

All scans independently assessed

All endpoints independently confirmed

C-30

0.0

0.2

0.4

0.6

0.8

1.0

0 90 180 270 360Time from randomization (days)

Pro

bab

ilit

y o

f n

ot

pro

gre

ssin

g


Placebo (n = 401)

Time to Disease ProgressionStudy M00-211 – ITT

P (G1,1) = .136

HR = 0.885 (95% CI = 0.755 – 1.037)

Scheduled radiographic scans

C-31

Survival Study M00-211 – ITT

0.0

0.2

0.4

0.6

0.8

1.0

0 180 360 540 720 900 1080 1260 1440Time from randomization (days)

Pro

ba

bili

ty o

f s

urv

iva

l

Atrasentan 10 mg

Placebo

P (G1,1) = .313

HR = 0.935 (95% CI = 0.796 – 1.100)

C-32

Metastatic Hormone Refractory Prostate Cancer Is a Disease of Bone

85% of patients with M+ HRPC have bone metastases

– Morbidity in HRPC is driven by bone metastases

Intractable pain

Skeletal events

Role of ET axis in osteoblastic bone metastases

– Tumor-ET-1/osteoblast-ETA interaction in bone

– ETA antagonism impacts bone metastases

85% of patients in M00-211 had bone metastases

– 690/809 randomized

– Baseline characteristics balanced between groups

C-33

Time to Disease Progression Study M00-211 – Patients With Bone Metastases

P = .016

HR = 0.813 (95% CI = 0.685 – 0.965)

0.0

0.2

0.4

0.6

0.8

1.0

0 90 180 270 360

Time from randomization (days)

Pro

ba

bil

ity

of

no

t p

rog

ress

ing


Placebo (n = 335)

C-34

Other Protocol-Specified Efficacy AnalysesStudy M00-211

Mean change in bone alkaline phosphatase

Mean change in PSA

Quality of life

C-35

Mean Change in Bone Alkaline Phosphatase Study M00-211

-10

0

10

20

30

40

50

4 8 12 Final

Atrasentan 10 mg

Placebo

-10

0

10

20

30

40

50

4 8 12 Final

Mea

n c

han

ge

fro

m b

asel

ine,

ng

/mL

Atrasentan 10 mg

Placebo

ITT Bone Metastases

***

** ***

***

**P < .01; ***P < .001

***

** **

***


Number of patientsAtrasentan

Placebo346369

334335

309308

364374

304308

292278

270253

320312

C-36

Mean Change in PSA Study M00-211

0

50

100

150

200

250

300

350

400

4 8 12 Final

Me

an

ch

an

ge

fro

m b

as

eli

ne

, n

g/m

L

Atrasentan 10 mg

Placebo

ITT Bone Metastases

**

**

*

*

0

50

100

150

200

250

300

350

400

4 8 12 Final

Atrasentan 10 mg

Placebo

**

***

*

*


*P < .05; **P < .01; ***P < .001

369383

351351

324319

384387

326322

308295

285265

338325


Placebo

C-37Atrasentan Has a Consistent Benefit in Quality of Life Compared to Placebo Study M00-211

Mean treatment difference in change from baseline to final assessment

(standardized 95% CI)

FACT-P

FACT-G

EORTC Global

PCS

Favors atrasentan

-5 -3 -1 0 1

ITTFavors atrasentan

-5 -3 -1 0 1

Bone Metastases

C-38

Mean Change in Prostate Cancer SubscoreStudy M00-211

-4

-2

0

2

4 8 12 Final

Me

an

ch

an

ge

fro

m b

as

elin

e

Atrasentan 10 mg

Placebo

ITT Bone Metastases

-4

-2

0

2

4 8 12 Final

Atrasentan 10 mg

Placebo

*


*P < .05; **P < .01

345360

305302

365369

304301

267250

322308

*

**


Placebo

*

C-39

0.0

0.2

0.4

0.6

0.8

1.0

0 90 180 270 360Time from randomization (days)

Pro

bab

ilit

y o

f n

ot

wo

rsen

ing

by

50%

Atrasentan 10 mg

Placebo

Time to 50% Worsening in PCS Pain ScoreStudy M00-211 – Patients With Bone Metastases

P = .003

HR = 0.644 (95% CI = 0.478 – 0.868)

C-40

Clinical Benefit of Atrasentan Consistent Benefit for Patients With Bone Metastases

0.4 0.6 0.8 1.00.2

Favors atrasentan

Hazard ratio (95% CI)

M00-211Time to disease progression

C-41

Clinical Benefit of Atrasentan Consistent Benefit for Patients With Bone MetastasesAcross Multiple Measures and Studies

0.4 0.6 0.8 1.00.2

Favors atrasentan



Radiographic

Clinical

C-42


0.4 0.6 0.8 1.00.2

Favors atrasentan



BAP progression

PSA progression

Radiographic

Clinical

C-43


0.4 0.6 0.8 1.00.2

Favors atrasentan



BAP progression

PSA progression

50% decline in FACT-P pain score (>56 days)

Opioid initiation (85 days)

Adverse event of bone pain (40 days)

Radiographic

Clinical

C-44


0.4 0.6 0.8 1.00.2

Favors atrasentan


M00-211M96-594

Time to disease progression

BAP progression

PSA progression




Radiographic

Clinical

1.4 1.61.2

C-45


Safety

C

Gary Gordon, MD

Oncology Vice PresidentAbbott Laboratories

C-46

Atrasentan Safety Experience

35 Abbott-sponsored studies – 1696 individuals received atrasentan (0.2 – 139.5 mg)– Healthy volunteers – Special populations– Prostate cancer patients

1159 prostate cancer patients received atrasentan– 676 in phase 2/3 placebo-controlled studies– Mean long-term exposure greater than 270 days– 584 treated for longer than 6 months– 294 treated for longer than 1 year

C-47

Atrasentan Is a Vasoactive Compound

Atrasentan is a targeted and potent ETA antagonist– Vasodilation– Fluid retention

Most adverse events were– Mild– Resolved

C-48

Overview of Adverse EventsPhase 2/3 Placebo-Controlled Studies(Studies M96-500, M96-594, M00-211)

Patients n (%)

Placebon = 544

Atrasentan 2.5 mgn = 136

Atrasentan 10 mgn = 541

Total adverse events 523 (96) 130 (96) 528 (98)

Grade 3/4 (severe) adverse events

218 (40) 55 (40) 221 (41)

Serious adverse events

152 (28) 48 (35) 173 (32)

Discontinuation due to adverse events

76 (14) 13 (10) 93 (17)

Death due to adverse events

28 (5) 9 (7) 31 (6)

C-49

*P < .05

Statistically Significant Adverse Events ≥ 10%Phase 2/3 Placebo-Controlled Studies

Patients, n (%)

Any Grade 3/4

Adverse EventPlacebon = 544

Atrasentan10 mgn = 541

Placebon = 544

Atrasentan 10 mgn = 541

Bone pain 277 (51)* 239 (44) 75 (14)* 49 (9)

Peripheral edema 76 (14) 208 (38)* 8 (1) 7 (1)

Rhinitis 73 (13) 185 (34)* 0 0

Headache 74 (14) 117 (22)* 2 (0.4) 4 (0.7)

Anemia 51 (9) 77 (14)* 19 (3) 22 (4)

Infection 39 (7) 61 (11)* 0 3 (0.6)

Dyspnea 21 (4) 56 (10)* 3 (0.6) 7 (1)

C-50

Cardiovascular Events

Arrhythmia

Heart failure– Adjudicator

John Teerlink, MD; Associate Professor of Medicine, University of California – San Francisco; Director, Heart Failure Clinic, Veterans Affairs Medical Center, San Francisco; Member of FDA Cardiovascular and Renal Drugs Advisory Committee

Myocardial infarction– Adjudicators

John Teerlink, MD Michael Parmacek, MD; Chief, Division of Cardiovascular

Medicine, Herbert C. Rorer Professor of Medical Sciences; University of Pennsylvania Medical Center

C-51

Arrhythmias

No arrhythmia seen in pre-clinical models

Few grade 3/4 events

No deaths resulting from arrhythmia

C-52

Arrhythmias Phase 2/3 Placebo-Controlled Studies

*P < .05

Patients, n (%)

Any Grade 3/4 (Severe)

Adverse eventPlacebon=544

Atrasentan10 mgn=541

Placebon=544

Atrasentan 10 mgn=541

Total Unique Patients 11 (2.0) 29 (5.4)* 3 (0.6) 4 (0.7)

Tachycardia 1 (0.2) 9 (1.7)* 0 0

Palpitation 2 (0.4) 6 (1.1) 0 0

Arrhythmia 2 (0.4) 3 (0.6) 1 (0.2) 0

Bradycardia 0 1 (0.2) 0 1 (0.2)

Extrasystoles 0 1 (0.2) 0 0

Ventricular extrasystoles 3 (0.6) 1 (0.2) 0 0

Ventricular tachycardia 0 0 0 0

Ventricular fibrillation 0 0 0 0

Atrial fibrillation 3 (0.6) 9 (1.7) 2 (0.4) 4 (0.7)

Atrial flutter 0 3 (0.6) 0 0

Supraventricular tachycardia 0 1 (0.2) 0 1 (0.2)

Supraventricular extrasystoles 0 1 (0.2) 0 0

C-53

Heart Failurea

Phase 2/3 Placebo-Controlled Studies

Patients, n (%)

Placebon = 544

Atrasentan2.5 mgn = 136


All events 5 (1) 5 (4) 23 (4)*

Grade 3/4 events 3 (1) 2 (1) 16 (3)*

Discontinuations 2 (0.4) 3 (2) 10 (2)*

Resulted in death 1 (0.2) 0 7 (1)*

a Includes heart failure, left heart failure, congestive heart failure, lung edema, and cardiogenic shock.* P < .05; statistical significance tested between placebo and 10 mg atrasentan.

Review of serious fluid-related events did not identify additional cases

C-54

Outcome of Heart FailurePhase 2/3 Placebo-Controlled Studies

18 resolved– 10 continued or interrupted atrasentan therapy– 8 discontinued atrasentan therapy

3 not resolved as of last follow-up

7 deaths attributed to heart failure by investigator– 4 adjudicated as cardiovascular events

2 had antecedent myocardial infarction– Abruptly discontinued -blockers

– 3 adjudicated as prostate cancer Minimal evidence of heart failure at death

C-55

Myocardial InfarctionPhase 2/3 Placebo-Controlled Studies

Patients, n (%)

Placebon = 544

Atrasentan2.5 mgn = 136


All events 2 (0.4) 0 9 (1.7)

Grade 3/4 events 2 (0.4) - 7 (1.3)

Discontinuations 2 (0.4) - 4 (0.7)

Resulted in death 1 (0.2) - 2 (0.4)

C-56Potential Preceding Events for Adjudicated Myocardial InfarctionPhase 2/3 Placebo-Controlled Studies (n = 10)

8/10 patients had history of underlying ischemic heart

disease

7/10 patients had one or more preceding events– Worsening angina (n = 4)

-blocker discontinuation (n = 2)

– Hemoglobin <10 g/dL (n = 4)

C-57

Summary of Cardiovascular Events

Arrhythmia– Few grade 3/4 events– No deaths

Heart failure/myocardial infarction– Adjudicated– Not under-reported– Most are manageable– Identifiable risk factors

C-58

Cardiovascular Safety Recommendations

As with other vasoactive compounds in the elderly– Consider cardiovascular risk factors

prior to therapy– Physician monitoring of patients with

cardiovascular risk factors and history– Treatment of volume overload and heart failure

C-59

Safety SummaryAtrasentan Is Generally Well-Tolerated

Extensive safety experience

Overall safety profile similar to placebo for grade 3/4 events, discontinuations, and deaths

Serious cardiovascular events are infrequent and with monitoring can be managed

No drug interactions warranting dose adjustment

No significant hepatic, renal, or marrow toxicities

C-60

Xinlay™ (atrasentan) Place in Therapy

Michael A. Carducci, MD

Co-Leader, Prostate Cancer ProgramDirector, Translational Drug DevelopmentKimmel Cancer Center at Johns Hopkins

C-61

Clinical Course of a Patient With HRPC and Bone Metastases Is Predictable

Most succumb to disease

Most experience symptoms of metastases

For those without symptoms, delaying the development of symptoms is an important goal of treatment

More options and choices are needed

Death fromother causes

Death from disease

Bonemetastases:

Hormone-refractoryAsymptomatic

Time

Bonemetastases:

Hormone-refractorySymptomatic

C-62

What Are the Options and What CanThey Achieve?

Symptoms present– Analgesics– Radiation therapy– Bisphosphonates– Radiopharmaceuticals– Chemotherapy

Mitoxantrone and prednisone Docetaxel-based chemotherapy

C-63

What Are the Options and What CanThey Achieve?

No symptoms– Secondary hormones

Simple Non-toxic

– Taxotere-based chemotherapy IV Survival benefit Timing is controversial Nearly all patients progress;

median TTP 6 months

Additional options are needed

C-64Consider a 68-Year-Old Male With Hormone Refractory Disease, Progressive Bone Metastases, and No Symptoms

6 Months One Year0 Months

C-65

His Future Illustrates the Clinical Dilemma

Further progression of disease

Pain that will require opiates is inevitable

At risk for– Significant morbidity from bone metastases –

pain and spinal cord compression– the medications needed to control the morbidity – Resulting in loss of mobility, fatigue, constipation,

weight loss, and an overall deterioration

C-66

The Clinical Dilemma

His goal

– Maintain quality of life for as long as possible

His question

– Are there additional options before or instead of chemotherapy?

– Are there more convenient treatment options?

– Are there any options that will delay progression?

C-67

Atrasentan Blocks the Osteoblastic Response in Bone

4

Atrasentan

Osteoblastic factors (ET-1)

Bone-derivedgrowthfactors

New bone

Prostate cancer cells

OsteoclastsMineralized bone matrix

Osteoblasts

Osteolyticfactors

ETA

C-68


0.4 0.6 0.8 1.00.2

Favors atrasentan


M00-211M96-594

Time to disease progression

BAP progression

PSA progression




Radiographic

Clinical

1.4 1.61.2

C-69


A novel targeted treatment for HRPC

Compelling scientific rationale

Extensively evaluated in randomized trials

Convenient once-daily oral therapy

Acceptable benefit-risk profile

C-1 Xinlay™ (atrasentan) Oncologic Drugs Advisory Committee September 13, 2005.

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Transcript of C-1 Xinlay™ (atrasentan) Oncologic Drugs Advisory Committee September 13, 2005.