18 November 2005 ODAC: DOXIL®, AIDS-related KS

Studies of DOXIL for AIDS-related KS(Pre-HAART)

Study No. Design

No. of pts. Objective Response Rate/Results

30-10 Phase 3 comparison to ABV

258 DOXIL (46.2%) vs. ABV (25.6%)

30-11 Phase 3 comparison to BV 241 DOXIL (58.7%) vs. BV (23.3%)

30-12 Open-label, non-comparative extension

871 DOXIL (65.9%) (n = 41 patients w/prior therapy)

30-14 Randomized, crossover, PK and tumor localization

43 DOXIL selectively accumulates into KS lesions

No significant differences in PK parameters b/w doses

30-21 Phase 1/2, cardiac biopsy data; comparison to cardiac damage

10 Less myocardial damage observed in patients treated with DOXIL compared to their matched doxorubicin controls

Note: A total of 10 DOXIL studies of varying design were completed for AIDS related KS

28 November 2005 ODAC: DOXIL®, AIDS-related KS

Publications of DOXIL for AIDS-related KS(HAART Era)

Study No. DesignDOXIL Treatment

(mg/m2)No. of pts. Results

Nunez Prospective, non-comparative, multicenter

DOXIL + HAART 79 79% response rate

Median time to response ~ 42 days

Martin-Carbonero

Randomized, open-label, multicenter

DOXIL 20mg/m2 every 3-weeks

28 20% HAART (N = 15)

76% HAART + DOXIL (N = 13)

Lichterfeld Uncontrolled, multicenter, observational study with matched controls

DOXIL + HAART 108 81.5% response rate

Recovery of CD4 counts not impaired by combination therapy

Hernandez Prospective, single arm, open-label, single center

DOXIL 20 mg/m2 every 3-weeks for 6 cycles

15 100% - GI response rate

53% Cutaneous response rate

38 November 2005 ODAC: DOXIL®, AIDS-related KS

Results of Randomized Studies of Liposomal Anthracyclines

NOTE: # = number; eval. = evaluable; A = Adriamycin (doxorubicin); B = bleomycin; V = vincristine; NS = not significant; NR = not reported. * includes complete and partial responses † this study reported mean survival times of 239 days for DOXIL, versus 160 days for bleomycin and vincristine.

Reference Treatment# entered

(# eval)Objective Response

Rate (%)*Time-to-treatment

failure (days)

Gill et al, 1996

DaunoXome 117 (116) 25%p=NS

115p=0.13

ABV 115 (111) 28% 99

Northfelt et al, 1998

DOXIL (2 Weeks) 133 (133) 46%

p<0.001124

p=0.26ABV 125 (125) 25% 128

Stewart, et al, 1998 †

DOXIL (3 Weeks) 121 (116) 59% p<0.001 160

p=NRBV 120 (102) 23% 157

48 November 2005 ODAC: DOXIL®, AIDS-related KS

Documentation for ACTG Criteria Biopsy Cutaneous lesions

– Number– Character (flat or raised)

Tumor-associated edema 3-5 marker lesions

– Bi-dimensional measurement Visceral lesions

– Radiographic evaluation – Bronchoscopy and endoscopy

58 November 2005 ODAC: DOXIL®, AIDS-related KS

Clinical Presentation of Patients Treated with DOXIL

Advanced KS with:– No prior HAART– HAART intolerant or failure– Virologic and immunologic response to HAART

Rapid KS progression on starting HAART (IRIS)

68 November 2005 ODAC: DOXIL®, AIDS-related KS

Response of Kaposi’s Sarcoma to DOXIL

78 November 2005 ODAC: DOXIL®, AIDS-related KS

Response of Kaposi’s Sarcoma to DOXIL

88 November 2005 ODAC: DOXIL®, AIDS-related KS

Response of Kaposi’s Sarcoma to DOXIL

98 November 2005 ODAC: DOXIL®, AIDS-related KS

Kaposi Sarcoma Incidence

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

5.5

1975

1976

1977

1978

1979

1980

1981

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

Year of diagnosis

Rat

e pe

r 100

,000 Study 30-38

Source: SEER Cancer Statistics Review, 1975-2002

AIDS-related KS approval