APP reports Abraxane(TM) is active in breast cancer patients who failed taxol or taxotere

06/07/04

Study results further support the thesis that biologically interactive protein nanoparticle enhances the therapeutic potential of taxane therapy

NEW ORLEANS, LA; SCHAUMBURG, IL – June 7, 2004 – Abraxis Oncology, a division of American Pharmaceutical Partners, Inc. (APP) (NASDAQ: APPX) today said that results from a 106 patient Phase II study of ABRAXANE in patients with advanced breast cancer whose disease had progressed while they were being treated with TAXOL® and Taxotere® responded to subsequent treatment with ABRAXANETM (albumin nanoparticle paclitaxel). The results were presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) in New Orleans, LA, by Joanne Blum, M.D., Ph.D., of the Charles A. Sammons Cancer Center, Baylor University Medical Center in Dallas, TX, one of 38 US Oncology affiliated practices that had patients participate in this clinical study of ABRAXANE.

The Phase II study, sponsored by American BioScience, included 106 patients with progressive metastatic breast cancer whose disease had progressed while being treated with TAXOL or Taxotere in the metastatic setting, or had a relapse within 12 months of adjuvant taxane therapy. The patients enrolled in this study had a very poor prognosis, with 91% having visceral (lung and liver) disease, 65% with more than three metastatic sites, and 88% demonstrating ongoing tumor growth while receiving TAXOL and/or Taxotere in the metastatic setting. Evidence of the activity of weekly doses of ABRAXANE in this highly refractory population is provided by the following findings:

  • A 15% overall response rate (95% CI: 8%-22%) in the 106 patients studied with a 38% probability of survival at 12 months based on analysis of data to date;
  • 40% of patients on treatment with ABRAXANETM were free of disease progression for as long as four months; and almost 30% for as long as six months;
  • Of those patients who progressed while on Taxotere alone in the metastatic setting (n=33), a 24% response rate was noted after receiving weekly ABRAXANETM;
  • Of those patients who progressed while on TAXOL alone in the metastatic setting (n= 31), a 16% response rate was noted after receiving weekly ABRAXANE.

"The demonstration that 15% of patients responded to ABRAXANETM treatment and that 30% had no disease progression after six months in this highly refractory breast cancer population that had progressed even while on TAXOL and/or Taxotere is an important finding. I think this drug has significant potential to benefit women with breast cancer," said Edith Perez, director of the breast cancer program at the Mayo Clinic in Jacksonville, FL.

The tolerability of this weekly regimen was demonstrated by the finding of <1% grade 4 febrile neutropenia and no grade 4 non-hematological toxicities. Grade 3 taxane associated toxicities were few, with <4% Gr3 sensory neuropathy, <3% Gr3 fatigue, <1% Gr3 edema, no Gr3 nail changes, no Gr3 myalgia and arthralgia, <1% Gr3 tearing, and no Gr3 hypersensitivity or flushing.

"I was very impressed not only by the activity of this drug but also by how well this weekly regimen of ABRAXANETM was tolerated in the breast cancer patients that I treated," said Dr. Joanne Blum, principal investigator of the study. "Several of my patients continued to receive weekly ABRAXANE for over a year, and one patient approached two years on this drug. This is impressive in this taxane refractory patient population. In our study, ABRAXANE was well tolerated with no grade 4 non-hematological toxicities and only a 4% incidence of grade 3 sensory neuropathy. ABRAXANE differentiates itself from other taxanes because it enables us to administer more cancer-fighting paclitaxel to the patient without the increase in side effects one might expect to see with currently available taxane therapies. It appears that ABRAXANE allows for more cancer fighting drug to be given to a patient, more of that drug to actually reach the tumor site in the body, and more of the drug to get inside of the tumor to fight cancer cells."

"This biologically interactive nanoparticle, through its novel albumin receptor-mediated mechanism of action, provides an opportunity to realize the full therapeutic potential of chemotherapeutic agents, while minimizing the drug's side effects, in the treatment of solid tumors. ABRAXANE, an albumin-bound nanoparticle form of paclitaxel, represents the first clinical proof of principle of this technology," said Patrick Soon-Shiong, M.D., Chairman, President and Chief Executive Officer of American Pharmaceutical Partners. "Our ultimate objective is to maximize the efficacy potential of chemotherapy including taxanes in cancer therapy – one of the most active anti-cancer agents discovered to date. However, due to the toxic solvents in current taxane preparations, the maximum dose that can be administered is limited. This may have significant implications on the course and ultimate outcome of treatment. If the active drug could be delivered to the tumor at the highest possible dose and for a long duration with the least amount of damage to normal tissue, the possibility exists that outcomes could be significantly improved.

"Recent studies have indicated that dose reduction during chemotherapy regimens may result in significant impairment of clinical outcome. The solvents used in currently approved taxanes contribute significantly to the toxicities of these drugs with resultant dose delays and reductions. By developing a nanoparticle form of a drug using a naturally–occurring human protein we have overcome the need for toxic solvents. The tolerability of this nanoparticle form was evident by the finding that 95% of cycles were given at the protocol specified dose of 100 mg/m², and that 91% of the patients were able to receive 100% of the planned dose of ABRAXANE at 100 mg/m2 administered weekly over 30 minutes with no dose reduction. Further, no grade 4 non-hematological toxicities and no severe hypersensitivity reactions, despite the absence of steroid pre-medication, occurred," said Soon-Shiong.

The company previously announced along with American BioScience Inc. that the New Drug Application (NDA) for ABRAXANETM was accepted for filing by the U.S. Food and Drug Administration (FDA), indicating the FDA has determined that the application is sufficiently complete to permit a substantive review. ABI and APP are strategic partners in the development, manufacture and marketing of ABRAXANE. ABI is responsible for the clinical development and registration of ABRAXANE. APP has licensed the exclusive North American manufacturing and marketing rights for ABRAXANE.

About Breast Cancer

According to the American Cancer Society (ACS), while early detection efforts have decreased mortality rates, in 2004 an estimated 215,990 women are expected to be diagnosed with breast cancer that had already spread. Breast cancer is still the leading overall cause of cancer death in women between the ages of 20 and 59, with 40,110 deaths estimated in 2004. One of every three cancers diagnosed in the United States is breast cancer; excluding skin cancer, breast cancer is the most common cancer among women.

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