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Patients Treated With Abraxane Achieve Better Tumor Response Rate, Longer Time to Progression Compared With Taxol

SCHAUMBURG, IL/SANTA MONICA, CA- December 05, 2003 -- American Pharmaceutical Partners, Inc. (NASDAQ: APPX), (APP) and ABRAXIS Oncology, the proprietary drug division of APP, today announced positive results of the randomized, controlled Phase III clinical trial in patients with metastatic breast cancer comparing the investigational product ABRAXANETM (formerly ABI-007) to the Cremophor® solvent-based TAXOL®. A detailed analysis of the study was presented by Joyce O'Shaughnessy, M.D., Co-Director, Breast Cancer Research and Director, Breast Cancer Prevention at Baylor-Charles A. Sammons Cancer Center, US Oncology in Dallas, Texas, and William Gradishar, M.D., FACP, Associate Professor of Medicine, Division of Hematology and Medical Oncology and Co-Director, Lynn Sage Breast Cancer Program at Northwestern University in Evanston, Illinois, to an audience of oncologists at a late-breaking session and Scientific Symposium at the San Antonio Breast Cancer Symposium held in San Antonio, Texas last Friday evening.

Patients with metastatic breast cancer receiving the solvent-free nanoparticle paclitaxel, ABRAXANETM (n=229 patients) achieved almost a doubling of the tumor response rate when compared to those patients receiving Bristol-Myers Squibb's TAXOL® (n=225). "The robustness of the data is underscored by the fact that statistically superior response rates with ABRAXANETM compared to TAXOL® were noted regardless of whether the data was assessed by the blinded, independent radiology review or the investigator assessment," said Joyce O'Shaughnessy, M.D.

Although the ABRAXANETM data and labeling remain subject to FDA review, the Phase III study demonstrated potentially important advantages over TAXOL® as a treatment for metastatic breast cancer patients, based on: higher response rates; longer time to tumor progression; absence of severe hypersensitivity reactions without the need for premedication; less neutropenia despite a higher dose infused over a shorter period of 30 minutes; and, a rapid recovery from sensory neuropathy compared with TAXOL®, albeit with a somewhat higher incidence consistent with the higher dosage administered.

Specifically, the results reported were as follows:

· A significantly higher Overall Tumor Response Rate (ORR) was noted in patients receiving ABRAXANE™ (33%) versus TAXOL® (19%), (p=0.001). Similarly, analysis of the Target Lesion Response Rate (TLRR) showed significantly higher anti-tumor activity (p · In patients receiving chemotherapy for metastatic breast cancer for the first time (first–line patients), a significantly higher tumor response was also noted, with 42% of ABRAXANE™ patients (n=97) responding to the therapy compared with a 27% response rate in patients (n=89) receiving TAXOL (p=0.029);

· Similarly, the response rates with ABRAXANE™ were higher, and statistically significant, when analyzed in those patients who had failed prior chemotherapy, and in patients with poor prognostic indicators such as in those with liver metastases (26%, n=92 vs. 13%, n=97) and lung metastases (43%, n=74 vs. 25%, n=79);

· A longer time to tumor progression was noted in patients receiving ABRAXANE™, with a median of 21.9 weeks versus a median progression time of 16.1 weeks after TAXOL, (p=0.030);

· 98% of cycles of ABRAXANE™ were administered without steroid premedication and no evidence of severe hypersensitivity reactions were noted in any of these patients thus confirming the ability to safely administer this solvent-free paclitaxel without the need for premedication. In contrast, 95% of the doses of TAXOL were administered with steroids and anti-histamines, and still these patients showed a significantly higher incidence of flushing than those patients receiving ABRAXANE without pre-medication;

· Both treatments were well tolerated with 98% of patients receiving the planned dose on both arms; the mean total paclitaxel dose delivered with ABRAXANE™ was 1459mg per patient per m2 and 909mg per patient per m2 with TAXOL;

· Consistent with this higher dose of paclitaxel delivered with ABRAXANE™, the incidence of Grade 3 sensory neuropathy was 10% versus 2% in the patients receiving TAXOL (p · Despite the higher dose of paclitaxel delivered, there was significantly less Grade 4 neutropenia with ABRAXANE™ (9%) compared to TAXOL (22%), providing the first clinical evidence that Cremophor may contribute to bone marrow damage and loss of white blood cells;

· Fluid retention was infrequent in both arms and there were no septic deaths in the study.

"It is clear that the solvent Cremophor is not an innocent bystander," said William Gradishar, M.D., the Principal Investigator of the study. "The findings of this Phase III clinical trial provide the first clinical evidence that Cremophor may be responsible not only for the severe hypersensitvity reactions that necessitate steroid pre-medication, but that the toxic effects of this solvent on patients may be more far-reaching than previously recognized. Data from this trial suggest that Cremophor itself may be responsible for the loss of protective white blood cells, by suppressing the bone marrow, and, furthermore, that the solvent-induced damage to nerve fibres, rather than paclitaxel itself, may account for the prolonged recovery of peripheral neuropathy noted with TAXOL®."

"We are extremely pleased that the increase in anti-tumor activity we had seen with ABRAXANETM in preclinical studies was confirmed in this Phase III trial, and further translated into an increased time to tumor progression in patients with metastatic breast cancer," said Michael J. Hawkins, M.D., Chief Medical Officer at American BioScience, Inc., the company responsible for developing ABRAXANETM.

"Our preclinical data indicated that higher intratumor concentrations of paclitaxel were achieved following administration of ABRAXANETM, compared to equal doses of TAXOL®. This effect, coupled with our ability to increase the dose of paclitaxel administered, predicted that ABRAXANETM would have more anti-tumor activity than TAXOL. This is now supported by the results of our randomized Phase III study. We will now expeditiously complete filing of the NDA, which has been granted fast-track designation."

ProtosphereTM Nanoparticle Albumin-Bound (nab) Technology - The Foundation Technology for ABRAXANETM
American BioScience's Protosphere Nanoparticle Albumin-Bound (nab) technology integrates biocompatible proteins with drugs to create the amorphous, nanoparticle form of the drug. These nanoparticles act as biologic nanotransporters for hydrophobic drugs such as paclitaxel, which may result in increased intracellular availability of the chemotherapeutic agent at the tumor site. At the San Antonio conference, American BioScience presented, for the first time, data that provides evidence of a novel receptor-mediated albumin-bound transporter mechanism for paclitaxel believed to play a role in increased penetration of the active drug into tumor tissue, by a mechanism of "transcytosis."

Source: American Pharmaceutical Partners, Inc.

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