SCHAUMBURG, Ill. and SANTA MONICA, Calif., Nov. 1 /PRNewswire-FirstCall/ -- American Pharmaceutical Partners, Inc. and American BioScience, Inc., announced today that the Journal of Clinical Oncology published data from the pivotal Phase III clinical trial pertaining to efficacy, safety and survival associated with ABRAXANE(TM) for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) in metastatic breast cancer.
The paper, titled: “Superior Efficacy of Albumin-Bound Paclitaxel, ABI-007, Compared With Polyethylated Castor Oil-Based Paclitaxel in Women With Metastatic Breast Cancer,” was released early online on Sept. 19, 2005. The significance of early online publications as characterized by the journal is that the article may be “expected to have a substantial and immediate impact on clinical practice.” The print version released today, titled: “Phase III Trial of Nanoparticle Albumin-Bound Paclitaxel Compared With Polyethylated Castor Oil-Based Paclitaxel in Women With Metastatic Breast Cancer,” may be found on the Journal of Clinical Oncology website at http://www.jco.org/cgi/content/abstract/23/31/7794. It reports that in this pivotal Phase III study, ABRAXANE almost doubled the response rate, and significantly prolonged the time to tumor progression (TTP) by more than a third compared with Taxol. The data are published in the November 1 print edition with an accompanying editorial (titled: Nanoparticle Albumin-Bound Paclitaxel for Metastatic Breast Cancer) that discusses the limitations of current taxane therapies in the treatment of metastatic breast cancer, describes the advantages of ABRAXANE, and recommends future studies (http://www.jco.org/cgi/content/full/23/31/7768).
(1) The U.S. Food and Drug Administration approved ABRAXANE(TM) (formerly ABI-007) in January 2005 for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated. For the full prescribing information for ABRAXANE(TM) please visit www.abraxane.com.
The objective of the Phase III trial was to confirm previous studies suggesting superior efficacy and reduced toxicity of ABRAXANE compared with standard paclitaxel (Taxol(R)) and to confirm the activity of ABRAXANE noted in a Phase II study in metastatic breast cancer patients. In this Phase II study, recently published in the September 1, 2005 issue of the Journal of Clinical Oncology titled: “Multicenter Phase II trial of ABI-007, an Albumin-Bound Paclitaxel, in Women with Metastatic Breast Cancer,” (http://www.jco.org/cgi/content/abstract/23/25/6019), the data demonstrated a response rate of 48% in all treated patients and a 64% response rate in patients who received ABRAXANE as first-line therapy (no prior treatment). In the pivotal Phase III trial, there was a trend for greater median survival for all patients treated with ABRAXANE than with Taxol. Although no statistical difference in survival was observed in first-line patients, a statistically significant prolongation in median survival by over two months was observed in patients who received ABRAXANE as second-line or greater therapy, compared with Taxol.
“In this Phase III trial, we demonstrated that ABRAXANE has a higher response rate and longer time to tumor progression in women with metastatic breast cancer as well as an increased survival in patients previously treated for metastatic disease,” said principal investigator and lead author William J. Gradishar, M.D., Professor of Medicine, Division of Hematology and Medical Oncology and Director of Breast Oncology at Northwestern Memorial Hospital. “In addition, ABRAXANE demonstrated a favorable safety profile compared with Taxol.”
“As a clinician, I’ve been very gratified to have another safe and highly effective treatment option for my patients with metastatic breast cancer,” said senior author Joyce A. O’Shaughnessy, M.D., co-director, Breast Cancer Research, and Director, Breast Cancer Prevention, at Baylor-Charles A. Sammons Cancer Center and US Oncology in Dallas, TX. “Because ABRAXANE is free of solvents that can cause severe toxicities such as life-threatening allergic reactions, it represents an important advance in the treatment of metastatic breast cancer. What I am most excited about, however, is the significant anti-tumor activity we are seeing with ABRAXANE.”
The incidence of Grade 4 neutropenia was significantly lower for ABRAXANE compared with Taxol despite a 49% higher paclitaxel dose. Febrile neutropenia was uncommon, and the incidence did not differ between the two study arms. On a dose accumulative basis, the average neuropathy score between ABRAXANE and Taxol did not differ. As expected with a higher dose of paclitaxel, treatment-related Grade 3 neuropathy was more common in the ABRAXANE arm than in the Taxol arm (10% versus 2%) but, in the ABRAXANE arm, these episodes improved to Grade 2 or 1 in a median 22 days when managed with interruption of treatment and dose reduction.
About the Pivotal Phase III Study
Four hundred fifty-four (454) patients were randomly assigned to 3-week cycles of either ABRAXANE 260 mg/m(2) intravenously without premedication (n=229) or Taxol 175 mg/m(2) intravenously with standard premedication (n=225). Selected study results follow:
* ABRAXANE demonstrated significantly higher response rates compared with Taxol for all patients (investigator assessed response rate) 33% v 19%, respectively; P = 0.001); patients who received first-line therapy (42% v 27%, respectively; P=0.029), patients who received second-line or greater therapy (27% v 13%, respectively; P=0.006), and patients who had received prior anthracycline therapy in either the adjuvant/metastatic setting (34% v 18%, respectively; P = 0.002) or the metastatic setting only (27% v 14%, respectively; P=0.010). * Median TTP was significantly longer with ABRAXANE than with Taxol for all patients (23.0 v 16.9 weeks, respectively; P = 0.006). * There was a trend for greater median survival for all patients treated with ABRAXANE than with Taxol (65.0 v 55.7 weeks, respectively; P = 0.374). Although no difference in survival was observed in first-line patients, the difference was statistically significant in patients who received ABRAXANE, compared with Taxol, as second-line or greater therapy (56.4 v 46.7 weeks, respectively; HR = 0.73; P = 0.024). * The incidence of Grade 4 neutropenia was significantly lower for ABRAXANE compared with Taxol (9% v 22%, respectively; P < 0.001) despite a 49% higher paclitaxel dose. * Febrile neutropenia was uncommon (< 2%) in both study arms, and no septic deaths occurred. * Grade 3 sensory neuropathy was more common in the ABRAXANE arm than in the Taxol arm (10% v 2%, respectively; P < 0.001) but these episodes improved with interruption of treatment to Grade 2 or 1 in a median 22 days and were easily managed with treatment interruption and dose reduction. * No severe (Grade 3 or 4) hypersensitivity reactions occurred with ABRAXANE despite the absence of premedication and shorter administration time. In contrast, Grade 3 hypersensitivity reactions occurred in the Taxol group despite standard premedication (chest pain, two patients; allergic reaction, three patients). * In subgroup analyses by age, the reported AEs were similar in patients less than 65 years old and patients greater than or equal to 65 years old in both groups. Of the patients greater than or equal to 65 years old, the incidences of the following AEs were notably lower in the ABRAXANE group than in the Taxol group: neutropenia (23% v 59%, respectively), leukopenia (10% v 31%, respectively), nausea (20% v 38%, respectively), hyperglycemia (0% v 19%, respectively), and flushing (0% v 16%, respectively).
In the randomized metastatic breast cancer study, the most important adverse events included neutropenia (all cases 80%; severe 9%), anemia (all 33%; severe 1%), infections (24%), sensory neuropathy (any symptoms 71%; severe 10%), nausea (any 30%; severe 3%), vomiting (any 18%; severe 4%), diarrhea (any 26%; severe < 1%), myalgia/arthralgia (any 44%; severe 8%), and mucositis (any 7%; severe < 1%). Other adverse reactions included asthenia (any 47%; severe 8%), ocular/visual disturbances (any 13%; severe 1%), fluid retention (any 10%; severe 0%), alopecia (90%), hepatic dysfunction (elevations in bilirubin 7%, alkaline phosphatase 36%, AST [SGOT] 39%), and renal dysfunction (any 11%; severe 1%). Thrombocytopenia (any 2%; severe < 1%), hypersensitivity reactions (any 4%; severe 0%), cardiovascular reactions (severe 3%), and injection site reactions (1%) were uncommon.
WARNING: ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. ABRAXANE therapy should not be administered to patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm(3). In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE.
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS.
The data reported for survival and time to tumor progression have been submitted to the FDA for review, but are not described in the currently approved labeling for ABRAXANE.
About American BioScience, Inc.
American BioScience, Inc. (ABI) is a privately held biotechnology company focused on the discovery, development and delivery of next-generation therapeutic moieties including biologically active molecules already existing within the human biological system, for the treatment of life-threatening diseases. ABI owns a majority interest in American Pharmaceutical Partners, Inc.
About American Pharmaceutical Partners, Inc.
American Pharmaceutical Partners, Inc. is a specialty drug company that develops, manufactures and markets injectable pharmaceutical products, focusing on the oncology, anti-infective and critical care markets. Abraxis Oncology, the proprietary division of APP, is devoted entirely to developing and promoting innovative, next-generation cancer therapies. For more information, visit APP’s website at www.appdrugs.com and www.abraxisoncology.com.
Because these forward-looking statements, whether expressed or implied, involve risks and uncertainties, there are important factors that could cause actual results to differ materially from those in the forward-looking statements. These factors include, without limitation, the timing of and costs associated with the ongoing launch of ABRAXANE(TM), the market adoption and demand of ABRAXANE, the fact that actual results achieved in further Phase II and III trials for ABRAXANE may or may not be consistent with results achieved to date, the difficulty in predicting the timing or outcome of other product research and development efforts, potential product characteristics and indications, marketing approvals and launches of other products, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing, the availability and pricing of ingredients used in the manufacture of pharmaceutical products, the ability to successfully manufacture products in a time-sensitive and cost effective manner, the acceptance and demand of new pharmaceutical products, the impact of patents and other proprietary rights held by competitors and other third parties. Additional relevant information concerning risks can be found in our Form 10-K for the year ended December 31, 2004 and other documents filed by us with the Securities and Exchange Commission.
Taxol(R) is a registered trademark of Bristol-Myers Squibb Company. Contacts: American Pharmaceutical Partners, Inc. Nicole Williams Executive Vice President & CFO (847) 969-2700 Rob Whetstone/Robert Jaffe PondelWilkinson Inc. (310) 279-5963
American Pharmaceutical Partners, Inc.
CONTACT: Nicole Williams, Executive Vice President & CFO of AmericanPharmaceutical Partners, Inc., +1-847-969-2700; or Rob Whetstone or RobertJaffe, both of PondelWilkinson Inc., +1-310-279-5963, for AmericanPharmaceutical Partners, Inc.
