This trial is the subject of a Special Protocol Assessment with the FDA, which means that the agency has previously agreed to study design, clinical endpoints and statistical analyses. Specifically, the FDA has stipulated that demonstrating statistically superior response rate of the nab-paclitaxel and carboplatin combination over the paclitaxel and carboplatin combination with an acceptable safety profile would be sufficient to submit a supplemental new drug application (sNDA) (as a 505(b)(2) submission) for approval of nab-paclitaxel in combination with carboplatin for the first-line treatment of NSCLC.Difficult-to-treat, NSCLC accounts for approximately 85 percent of all lung cancer cases. The American Cancer Society (ACS) estimates that approximately 219,440 people will be diagnosed with lung cancer in the United States in 2009, and that approximately 159,000 deaths occur each year due to this cancer. 4 About the Study Results of a Randomized, Phase 3 Trial of nab-Paclitaxel (nab-P) and Carboplatin (C) Compared With Cremophor-based Paclitaxel (P) and Carboplatin as First-line Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) (Abstract # LBA7511) In this phase 3 study, 1,052 patients with advanced NSCLC were treated. Patients were diagnosed with histologically or cytologically confirmed stage IIIB or IV NSCLC, had not received prior treatment for metastatic disease and had an Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) of 0-1. Patients were randomized 1:1 to a treatment regimen that consisted of six cycles of carboplatin AUC 6 on day 1 of a three-week treatment cycle in combination with either nab-paclitaxel (100 mg/m 2) weekly or cremophor-based paclitaxel (200 mg/m 2) every three weeks until disease progression or unacceptable toxicity. The primary endpoint for this study was disease response, measured as CR and PR as defined by RECIST criteria. The secondary endpoint was progression-free survival (PFS). An independent radiologist review showed nab-paclitaxel was well-tolerated and provided a significant improvement in overall response rate as compared with Taxol, both administered in combination with carboplatin. PR or CR was demonstrated in 170 patients (33 percent) receiving the nab-paclitaxel combination versus demonstrated response in 132 patients (25 percent) (p=0.005) treated with the paclitaxel combination. Histologic analysis showed significantly improved ORR for nab-paclitaxel versus paclitaxel in squamous cell carcinoma patients (41 percent versus 24 percent, p<.001), a 67 percent improvement, and comparative effectiveness in patients with non-squamous histology (ORR of 26 percent versus 25 percent respectively). The safety results were generally consistent with the known safety profile of nab-paclitaxel. The most common grade 3 and 4 adverse events that occurred were neutropenia (45 percent), anemia (27 percent), leucopenia (22 percent) and thrompocytopenia (17 percent). Of particular note, there was significantly less sensory neuropothy in the nab-paclitaxel versus the paclitaxel (3 percent versus 10 percent, p<.001). Other grade 3 and 4 adverse events observed included myalgia, anorexia, nausea, fatigue, and alopecia. There were no cases of grade 3 or 4 arthralgia. About nab ® -Driven Chemotherapy Abraxis BioScience has developed a proprietary n anoparticle a lbumin- b ound ( nab) technology which leverages albumin nanoparticles for the active and targeted delivery of chemotherapeutics to the tumor. This nab-driven chemotherapy provides a new paradigm for penetrating the blood-stroma barrier to reach the tumor cell. The proposed mechanism of delivery of this nab-driven chemotherapy is thought to be by targeting a previously unrecognized tumor-activated, albumin-specific biologic pathway with a nanoshell of the human blood protein albumin. This nano-shuttle system is believed to activate an albumin-specific (Gp60) receptor-mediated transcytosis path through the cell wall of proliferating tumor cells, using caveolin-1 activated caveolar transport. Once in the stromal micro-environment, the albumin-bound drug may be preferentially localized by a second albumin-specific binding protein, SPARC, a protein secreted into the stroma by tumor cells. The resulting collapse of stroma surrounding the tumor cell may thus enhance the delivery of the nab-chemotherapeutic to the intracellular core of the tumor cell itself. About ABRAXANE ® ABRAXANE is the first clinical validation of the nanoparticle albumin bound ( nab) technology platform and is a treatment option for metastatic breast cancer. This protein-bound chemotherapy agent combines paclitaxel with albumin, a naturally-occurring human blood protein. ABRAXANE is currently in various stages of investigation for the treatment of the following cancers: expanded applications for metastatic breast, non-small cell lung, malignant melanoma, pancreatic and gastric. The U.S. Food and Drug Administration approved ABRAXANE for Injectable Suspension (paclitaxel protein albumin-bound particles for injectable suspension) (albumin-bound) 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 please visit http://www.abraxane.com. IMPORTANT SAFETY INFORMATION The use of ABRAXANE has not been studied in patients with hepatic or renal dysfunction. In the randomized controlled trial, patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum creatinine >2 mg/dL.
ABRAXANE can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with ABRAXANE.Men should be advised to not father a child while receiving treatment with ABRAXANE. It is recommended that nursing be discontinued when receiving ABRAXANE therapy. ABRAXANE contains albumin (human), a derivative of human blood. Caution should be exercised when administering ABRAXANE concomitantly with known substrates or inhibitors of CYP2C8 and CYP3A4. ABRAXANE therapy should not be administered to patients with metastatic breast cancer who have baseline neutrophil counts of less than 1,500 cells/mm3. It is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE. Patients should not be retreated with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. In the case of severe neutropenia (<500 cells/mm3 for 7 days or more) during a course of ABRAXANE therapy, a dose reduction for subsequent courses is recommended. Sensory neuropathy occurs frequently with ABRAXANE. If grade 3 sensory neuropathy develops, treatment should be withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE. Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3% of patients in the randomized trial. These events included chest pain, cardiac arrest, supraventricular tachycardia, edema, thrombosis, pulmonary thromboembolism, pulmonary embolism, and hypertension. In the randomized metastatic breast cancer study, the most important adverse events included alopecia (90%), neutropenia (all cases 80%; severe 9%), sensory neuropathy (any symptoms 71%; severe 10%), asthenia (any 47%; severe 8%), myalgia/arthralgia (any 44%; severe 8%), anemia (all 33%; severe 1%), infections (24%), nausea (any 30%; severe 3%), vomiting (any 18%; severe 4%), diarrhea (any 27%; severe <1%), and mucositis (any 7%; severe <1%).
Other adverse reactions have included ocular/visual disturbances (any 13%; severe 1%), fluid retention (any 10%; severe 0%), hepatic dysfunction (elevations in bilirubin 7%, alkaline phosphatase 36%, AST [SGOT] 39%), 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%). During postmarketing surveillance, rare occurrences of severe hypersensitivity reactions have been reported with ABRAXANE.About Abraxis BioScience, Inc. Abraxis BioScience is a fully integrated global biotechnology company dedicated to the discovery, development and delivery of next-generation therapeutics and core technologies that offer patients safer and more effective treatments for cancer and other critical illnesses. The company's portfolio includes chemotherapeutic compound (ABRAXANE ® ), which is based on the company's proprietary tumor targeting technology known as the nab ® platform. The first FDA approved product to use this nab platform, ABRAXANE, was launched in 2005 for the treatment of metastatic breast cancer and is now approved in 39 countries. The company continues to expand the nab platform through a robust clinical program and deep product pipeline. Abraxis trades on the NASDAQ Global Market under the symbol ABII. For more information about the company and its products, please visit www.abraxisbio.com. FORWARD-LOOKING STATEMENTS The statements contained in this press release that are not purely historical are forwardlooking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements in this press release include statements regarding our expectations, beliefs, hopes, goals, intentions, initiatives or strategies, including statements regarding the clinical development plan, and the timing and scope of clinical studies and trials, for ABRAXANE and the global commercialization of ABRAXANE. Because these forward-looking statements involve risks and uncertainties, there are important factors that could cause actual results to differ materially from those in the forwardlooking statements. These factors include, without limitation, the fact that results from preclinical studies may not be predictive of results to be obtained in other pre-clinical studies or future clinical trials; delays in commencement and completion of clinical studies or trials, including slower than anticipated patient enrollment and adverse events occurring during the clinical trials; decisions by regulatory authorities regarding whether and when to approve ABRAXANE or product candidates for various indications as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of ABRAXANE and other products and product candidates; unexpected safety, efficacy or manufacturing issues with respect to ABRAXANE or product candidates; the need for additional data or clinical studies for ABRAXANE or product candidates; regulatory developments (domestic or foreign) involving the company’s manufacturing facilities; the market adoption and demand of ABRAXANE and other products, the costs associated with the ongoing launch of ABRAXANE; research and development associated with the nab ® technology platform; 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; and the impact of patents and other proprietary rights held by competitors and other third partie s. Additional relevant information concerning risks can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2009 and in other documents it has filed with the Securities and Exchange Commission. The information contained in this press release is as of the date of this release. Abraxis assumes no obligations to update any forward-looking statements contained in this press release as the result of new information or future events or developments.
TAXOL® is a registered trademark of Bristol-Myers Squibb Company.1 Kelly K et al. “Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Vinorelbine Plus Cisplatin in the Treatment of Patients With Advanced Non–Small-Cell Lung Cancer: A Southwest Oncology Group Trial.” Journal of Clinical Oncology. 2001: Vol 19, No 13 (July 1): pp 3210-3218. 2 Schiller JH et al. “Comparison of Four Chemotherapy Regimens for Advanced Non–Small-Cell Lung Cancer.” The New England Journal of Medicine. 2002: Vol 346, No. 2 (January 10): pp 92-98. 3 Sandler A et al. “Paclitaxel–Carboplatin Alone or with Bevacizumab for Non–Small-Cell Lung Cancer.” The New England Journal of Medicine. 2006: Vol 355, No. 24 (December 14): pp 2542-50. 4 Cancer Facts & Figures 2008. American Cancer Society publication. http://www.cancer.org/downloads/STT/500809web.pdf.