Physician Assessment of Peripheral NeuropathyNCI CTC Grade—Cumulative Dose

0

1

2

3

4

0 250 500 750 1000 1250 1500

Cumulative Dose (mg/m²)Source: NDA Addendum.Note: P-value from treatment by dose interaction effect from the following repeated measures model:Y = Treatment Patient (Treatment) Dose Treatment *Dose.

Abraxane (N = 229)Taxol (N = 225)P-value = 0.250

NC

I CTC

Gra

de

NE-7

Patient Assessment of Peripheral NeuropathyTotal Score by Cumulative Dose

0123456789

101112131415

0 250 500 750 1000 1250 1500

Cumulative Dose (mg/m²) Source: NDA Addendum.Note: P-value from treatment by dose interaction effect from the following repeated measures model:Y = Treatment Patient (Treatment) Dose Treatment *Dose.

Abraxane (N = 229)Taxol (N = 225)P-value = 0.202

Tota

l Sco

re

NE-8

Patients with Grade 3 Sensory Neuropathy: Time to Improvement to Grade 1 or 2 (Based on AE Data)

0.00

0.25

0.50

0.75

1.00

0 10 20 30 40 50 60 70 80 90 100 110 120 130

Time to Improvement (Days)Source: NDA Addendum.Note: P-value from log-rank test.

Abraxane (N = 24)Taxol (N = 5)CensoredP-value = 0.028

Prop

ortio

n N

ot Im

prov

ed

NE-9

Examples of Drugs Approved as 505(b)(2) NDAs

RLD 505(b)(2) ProductTaxol® (paclitaxel) Injection (BMS)

Abraxane® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) (Abraxis BioScience, Inc.)Change to an approved drug (different excipient)

Genotropin (somatropin for injection) (Pfizer)

Omnitrope™ (somatropin [rRNA origin]) for injection (Sandoz, Inc.)Change to an approved drug (follow-on protein/recombinant source)

Premarin (conjugated estrogen tablets, USP) (Wyeth)

Cenestin tablets (estrogens, conjugated synthetic A) (Duramed)Change to an approved drug (immediate release tablet/synthetic estrogens)

RG-2

CA008: Summary of Paclitaxel PharmacokineticParameters for Abraxane and Taxol

Source: Abraxane NDA

PK-3

Biodistribution of Abraxane andTaxol Are Similar

PK-11

Time to Progression Analysis for Phase 3 Study

The following two analyses of TTP have been conducted:

1. TTP based on all on-therapy Investigator response assessments.• post-approval commitment, June 2005

2. TTP based on the Independent Radiology Laboratory (IRL) response assessments and Investigator response assessments• labeling supplement, July 2006• It makes use of all available response assessments

including the IRL assessments for cycles 1–6 and all Investigator assessments, and

• It uses a conservative approach through cycles 1–6 by selecting the earliest date of progression between the IRL assessments and Investigator assessments

• These TTP data are currently under review with the FDA

TI-1

Abraxane Prolonged Time to Tumor ProgressionCA012: Secondary Endpoint

0.00

0.25

0.50

0.75

1.00

0 10 20 30 40 50 60 70 80 90 100 110 120Week

Note: P-value from log-rank test.

Abraxane (N = 229)Taxol (N = 224)P-value = 0.002HR = 0.726

Prop

ortio

n N

ot P

rogr

esse

d

0.00

0.25

0.50

0.75

1.00

0 10 20 30 40 50 60 70 80 90 100 110 120Week

Abraxane (N = 233)Taxol (N = 227)P-value = 0.002Hazard Ratio = 0.721

Investigator assessmentJune 2005

(NDA Post marketing commitment)

Time to Tumor Progression Time to Tumor Progression

Investigator assessment+

Independent radiology reviewJuly 2006

(Labeling supplement)

TI-2

Time to Disease ProgressionBlinded Independent Radiology Laboratory Assessment

0.00

0.25

0.50

0.75

1.00

0 4 8 12 16 20 24

WeekSource data on file Abraxis BioScienceNote: P-value from log-rank test.

Abraxane (N = 215)Taxol (N = 214)P-value = 0.003HR = 0.519

Prop

ortio

n no

t Pro

gres

sed

TI-3