D-1Bisphosphonate Bone Metastases TrialsProportion of Patients With Any SRE§

(12, 010)

Patients, %

Treatment N 3 mo 6 mo 9 mo 12 mo

Pamidronate Study 12 Pam 90 mg 198 10 21 24 28 Placebo 179 21 32 41 44

ZOMETA® Study 010 ZOMETA 4 mg 183 31 38 40 47 ZOMETA 8/4 mg 160 31 39 45 49 Pam 90 mg 167 25 40 45 49

42

§Intent-to treat.

D-2Bisphosphonate Bone Metastases Trials Demographic and Prognostic Variables(12, 010)

Pamidronate Study 12 ZOMETA® Study 010

Pam ZOMETA ZOMETA Pam 90 mg Placebo 4 mg 8/4 mg 90 mg

Variable N = 198 N = 179 N = 183 N = 160 N = 167

Age, yrMean ± s.d. 64.1 ± 9.4 62.7 ± 10.1 63.1 ± 10.52 62.2 ± 11.37 62.6 ± 11.41Median 66.0 63.0 62.0 63.0 62.0

Time from initialdiagnosis to Visit 2, mo Mean ± s.d. 30.5 ± 32.2 27.7 ± 33.5 18.0 ± 32.24 13.5 ± 21.75 17.3 ± 28.62

Median 19.3 14.4 2.8 2.6 2.7

42

D-3Bisphosphonate Bone Metastases Trials Proportion of Patients With Pathologic Fractures§

(12, 010)

Pamidronate Study 12:Proportion of patients with pathologic fracture in the 3 mo prior to study entry

Time from diagnosis Without pathologic With pathologicto study entry N fractures, % fractures, %

6 mo 115 75 25

> 6 mo 277 90 10

ZOMETA® Study 010: Proportion of pamidronate patients with pathologic fracture

Time from diagnosis Patients, %to study entry N 3 mo 6 mo 9 mo 13 mo

6 mo 104 21 38 40 45

> 6 mo 62 15 24 32 37

42

§Intent-to treat.

D-4

Patients With Any SRE up to End-of-Core by Race (010, 011, 039)

Patients, n/N (%)

Study ZOMETA® ZOMETA Pam 90 mg/ number Race 4 mg 8/4 mg placebo

010 N = 561 N = 524 N = 555White 225/493 (46) 206/443 (47) 234/484 (48)Black 10/34 (29) 22/42 (52) 13/43 (30)Other 13/34 (38) 14/39 (36) 10/28 (36)

011 N = 257 N = 266 N = 250White 91/229 (40) 85/238 (36) 103/226 (46)Black 4/15 (27) 4/15 (27) 4/12 (33)Other 2/13 (15) 3/13 (23) 4/12 (33)

039 N = 214 N = 221 N = 208White 64/178 (36) 69/186 (37) 77/172 (45)Black 4/24 (17) 7/19 (37) 8/19 (42)Other 3/12 (25) 9/16 (56) 7/17 (41)

54

D-5

908084

0

20

40

60

80

100

Pe

rce

nt

wit

h C

R

ZOMETA® Efficacy in Bone Metastases

3338

44

35

4644 44 46

38

0

10

20

30

40

50

Per

cen

t w

ith

SR

E (

–HC

M)

ZOMETA® 4 mg ZOMETA 8/4 mg Placebo Pam 90 mg

Prostate cancer(039)

Solid tumors–PC/BC

(011)

Breast cancer andmultiple myeloma

(010)

N = 214 221 208 257 266 250 564 526 558

29

HCM(036, 037)

44 42 36

D-6Solid Tumors – PC/BCAntineoplastic Therapies After Start of Study Drug (011)

Patients, n (%)

ZOMETA® ZOMETA4 mg 8/4 mg Placebo

Antineoplastic therapy N = 254 N = 265 N = 247

37

Any 192 (75.6) 184 (69.4) 181 (73.3)Carboplatin 74 (29.1) 58 (21.9) 65 (26.3)Paclitaxel 52 (20.5) 58 (21.9) 46 (18.6)Gemcitabine hydrochloride 39 (15.4) 28 (10.6) 25 (10.1)Cisplatin 37 (14.6) 46 (17.4) 41 (16.6)

PT

T 8

.2-4

D-7Breast Cancer and Multiple MyelomaFrequency Distribution of Antineoplastic Regimens (010) (1)

Patients, n (%) ZOMETA® ZOMETA Pam

No. of 4 mg 8/4 mg 90 mg Stratum regimen N = 563 N = 524 N = 556

37

Multiple myeloma, n 186 160 167 0 11 (5.9) 10 (6.3) 11 (6.6) 1 74 (39.8) 58 (36.3) 72 (43.1) 2 43 (23.1) 43 (26.9) 41 (24.6) 3 29 (15.6) 31 (19.4) 21 (12.6) 4 17 (9.1) 11 (6.9) 12 (7.2) 5 12 (6.5) 7 (4.4) 10 (6.0)

PT

T 8

.2-7

D-8Breast Cancer and Multiple MyelomaFrequency Distribution of Antineoplastic Regimens (010) (2)

Patients, n (%) ZOMETA® ZOMETA Pam

No. of 4 mg 8/4 mg 90 mg Stratum regimen N = 563 N = 524 N = 556

37

Breast cancer with chemotherapy, n 176 169 179

0 3 (1.7) 5 (3.0) 6 (3.4) 1 53 (30.1) 51 (30.2) 58 (32.4) 2 61 (34.7) 65 (38.5) 56 (31.3) 3 34 (19.3) 22 (13.0) 35 (19.6) 4 11 (6.3) 17 (10.1) 16 (8.9) 5 14 (8.0) 9 (5.3) 8 (4.5)

Breast cancer withhormonal therapy, n 201 195 210

0 3 (1.5) 1 (0.5) 3 (1.4) 1 93 (46.3) 114 (58.5) 91 (43.3) 2 59 (29.4) 48 (24.6) 69 (32.9) 3 32 (15.9) 19 (9.7) 34 (16.2) 4 7 (3.5) 7 (3.6) 8 (3.8) 5 7 (3.5) 6 (3.1) 5 (2.4)

PT

T 8

.2-7

D-9Solid Tumors – PC/BCFrequency Distribution of Antineoplastic Regimens (011)

Patients, n (%)

ZOMETA® ZOMETANo. of 4 mg 8/4 mg Placebo

Stratum regimen N = 254 N = 265 N = 247

37

Non small cell lung cancer, n 120 130 117 0 20 (16.7) 29 (22.3) 25 (21.4) 1 50 (41.7) 65 (50.0) 67 (57.3) 2 36 (30.0) 24 (18.5) 16 (13.7) 3 9 (7.5) 6 (4.6) 5 (4.3) 4 5 (4.2) 3 (2.3) 3 (2.6) 5 0 (0) 3 (2.3) 1 (0.9)

Other solid tumors, n 134 135 130 0 42 (31.3) 52 (38.5) 41 (31.5) 1 61 (45.5) 60 (44.4) 54 (41.5) 2 22 (16.4) 17 (12.6) 29 (22.3) 3 8 (6.0) 3 (2.2) 4 (3.1) 4 1 (0.7) 3 (2.2) 1 (0.8) 5 0 (0) 0 (0) 1 (0.8)

PT

T 8

.2-7

D-10Solid Tumors –PC/BCTime to First SREDeaths and Dropouts Considered SREs (011)

Median time, P-value N (%)§ days vs placebo

ZOMETA® 4 mg 257 (73) 127 .006

ZOMETA 8/4 mg 266 (80) 105 .184

Placebo 250 (82) 85

§Kaplan-Meier estimate of the proportion at Month 9.

D-11Breast Cancer and Multiple Myeloma Time to First SREDeaths and Dropouts Considered SREs (010)

Median time, P-value N (%)§ days vs Pam 90

mg

ZOMETA® 4 mg 561 (58) 312 .099

ZOMETA 8/4 mg 555 (59) 265 .545

Pam 90 mg 524 (61) 252

§Kaplan-Meier estimate of the proportion at Month 13.

D-12Prostate Cancer Time to First SREDeaths and Dropouts Considered SREs (039)

Median time, P-value N (%)§ days vs placebo

ZOMETA® 4 mg 214 (66) 337 .030

ZOMETA 8/4 mg 221 (74) 195 .924

Placebo 208 (73) 221

§Kaplan-Meier estimate of the proportion at Month 15.

D-13

Cumulative Incidence Rate of SREAll Patients§ (039)

0.0

0.2

0.4

0.6

0.8

1.0

0 60 120 180 240 300 360 420

Time after start of study drug, days

Cu

mu

lati

ve

inc

ud

en

ce

ra

te

ZOMETA 4 mg 214 180 149 113 97 85 70 45ZOMETA 8/4 mg 221 177 132 102 77 61 46 34Placebo 208 171 128 103 78 64 43 31

Median time, days

ZOMETA® 4 mg NR P = .013ZOMETA 8/4 mg NR P = .357Placebo 337

03

9 P

TF

9.2

-52

p3

21

§Intent-to-treat.NR = Not reached.

D-14

Prostate CancerMedian Serum PSA Level (Observed) (039)

0

40

80

120

160

200

0 2 4 6 8 10 12 14 16

Time on study, mo

Med

ian

ser

um

PS

A,

ng

/mL

ZOMETA 4 mg 212 150 162 132 85 102 90 60 67ZOMETA 8/4 mg 218 158 156 146 69 106 74 45 53Placebo 200 145 152 139 72 102 77 49 51

ZOMETA® 4 mg ZOMETA 8/4 mg Placebo

03

9 P

TF

9.2

-56

54

D-15

Prostate CancerTotal Number of SREs (039)

With 21-day window Without 21-day window

ZOMETA® ZOMETA4 mg Placebo 4 mg Placebo

SRE (+HCM) 112 155 167 258SRE 112 155 167 256Pathologic fracture 34 54 46 84

Vertebral fracture 10 20 10 30Nonvertebral fracture 25 38 36 54

Radiation to bone 65 85 90 130Surgery to bone 5 8 5 8Spinal cord compression 10 15 13 17Change to antineoplastic

therapy 13 17 13 17Hypercalcemia 0 2 0 2

56P

ro 0

1 1 P

TT

9.2

- 6x x

D-16

Cumulative Incidence Rate of SREAll Patients§ (011)

0.0

0.2

0.4

0.6

0.8

1.0

0 60 120 180 240

Time after start of study drug, days

Cu

mu

lati

ve

inc

ide

nc

e r

ate

ZOMETA 4 mg 257 173 107 62 46ZOMETA 8/4 mg 266 177 99 56 40Placebo 250 152 81 48 36

Median time, days

ZOMETA® 4 mg 314 P = .044ZOMETA 8/4 mg NR P = .037Placebo 185

01

1 P

TF

9.2

-52

p3

20

§Intent-to-treat.NR = not reached.

D-17

Solid Tumors –PC/BCTotal Number of SREs (011)

With 21-day window Without 21-day window

ZOMETA® ZOMETA4 mg Placebo 4 mg Placebo

SRE (+HCM) 131 163 201 275SRE 131 156 201 267Pathologic fracture 48 63 69 95

Vertebral fracture 21 32 27 41Nonvertebral fracture 31 34 42 54

Radiation to bone 79 101 112 153Surgery to bone 12 9 12 9Spinal cord compression 7 10 8 10Hypercalcemia 0 8 0 8

56P

ro 0

1 1 P

TT

9.2

- 6x x

D-18

Breast Cancer and Multiple MyelomaTotal Number of SREs (010)

With 21-day window Without 21-day window

ZOMETA® Pam ZOMETA Pam4 mg 90 mg 4 mg 90 mg

SRE (+HCM) 411 451 808 849SRE 408 440 801 835Pathologic fracture 301 292 622 584

Vertebral fracture 131 133 202 214Nonvertebral fracture 206 198 420 370

Radiation to bone 105 143 141 196Surgery to bone 23 36 25 37Spinal cord compression 12 16 13 18Hypercalcemia 7 14 7 14

56P

ro 0

1 1 P

TT

9.2

- 6x x