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Data from Multiple Studies Evaluating ABRAXANE in the Treatment of Advanced Melanoma among 31 Abraxis Abstracts Featured During 46th Annual Meeting of the American Society of Clinical Oncology
Abraxis BioScience, Inc. (NASDAQ:ABII) presented trial design information from its ongoing phase 3 registration trial of nanoparticle albumin bound (nab«) driven chemotherapy, nab-paclitaxel (ABRAXANE« for Injectable Suspension; paclitaxel albumin protein-bound particles for injectable suspension), in melanoma, an aggressive form of skin cancer that affects more than 68,000 people in the U.S. each year. Melanoma is the leading cause of skin cancer death in the United States, killing more than 8,000 people annually.i
Abraxis BioScience also presented an abstract describing the design of its ongoing phase 3 registrational trial of nab-paclitaxel for the treatment of metastatic malignant melanoma (MMM). The pivotal phase 3 clinical trial program exploring the use of nab-paclitaxel (150 mg/m2) in advanced melanoma was discussed during the "Trials in Progress" session at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
New data on Abraxis BioScience's novel nab technology, which leverages albumin nanoparticles for the active and targeted delivery of chemotherapeutics to the tumor, has been presented at ASCO in a wide range of tumor types, including pancreatic, ovarian, breast, head and neck, and non-small cell lung cancers. The company is investigating the potential of nab-driven chemotherapy to deliver cytotoxic agents directly to the tumor microenvironment through a previously unrecognized tumor-activated, albumin-specific biologic pathway in the most difficult-to-treat cancer types, including metastatic malignant melanoma.
"As the body of evidence continues to build it validates our commitment to interrogating the activity of ABRAXANE in difficult-to-treat tumor types such as metastatic melanoma," said Patrick Soon-Shiong, M.D., Executive Chairman and Founder of Abraxis BioScience.
Currently approved for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy, ABRAXANE has also been granted orphan drug designation by the Food and Drug Administration for the treatment of stage IIB-IV melanoma as well as pancreatic cancer.
About the Studies
I. An open-label, multicenter, phase 3 trial of nab-paclitaxel (NP) vs dacarbazine (DTIC) in previously untreated patients (PTs) with metastatic malignant melanoma (MMM) (Abstract #TPS314)
In this ongoing phase 3 registration trial, cytotoxic chemotherapy-na´ve patients with metastatic malignant melanoma are randomized into two treatment arms consisting of either nab-paclitaxel (150 mg/m2) on days 1, 8, and 15 every 4 weeks or dacarbazine (1000 mg/m2) on day 1 every 21 days. The primary efficacy endpoint is progression-free survival (PFS) and the main secondary endpoint is overall survival (OS). Other secondary endpoints include safety and tolerability of the regimens, nab-paclitaxel pharmacokinetic parameters, effects of therapy on and the relationship of response to the levels of SPARC and gene methylation, mutational and other biomarkers, response rate, stable disease rate at greater than or equal to 16 weeks and duration of response. Dosage reductions of nab-paclitaxel to 120 and 90 mg/m2 and of dacarbazine to 800 and 600 mg/m2 and the use of filgrastim for neutropenic fever are allowed. Efficacy is assessed by CT scans every eight weeks in both arms. The study accrual goal is 514 patients, randomized to 257 patients per treatment arm. A total of 104 multinational sites are anticipated. Currently 34 sites are open and accrual is on schedule with 135 patients enrolled. .
II. Tumor SPARC microenvironment signature (SMS) and plasma levels in a phase II trial of unresectable stage IV melanoma treated with nab-paclitaxel and carboplatin: a translational study of NCCTG trial N057E (Abstract #8578)
In this Phase II study, 76 patients with unresectable stage IV melanoma who were either chemotherapy na´ve or pretreated were given therapy. The treatment regimen consisted of nab-paclitaxel (100 mg/m2) and carboplatin (AUC 2) on days 1, 8 and 15 of a 28-day cycle until disease progression. SPARC in tumor biopsies was measured using a validated SPARC IHC. The primary objective was to use the developed SMS to distinguish between low risk and high risk groups with respect to PFS and OS. Tumor SPARC IHC data was available for 40 patients, suggesting that SPARC in the tumor microenvironment may play an important role in the outcome of melanoma patients:
* A unique SPARC signature was developed for melanoma patients to distinguish early progressers (LR, n=9) from later progressers (HR, n=31)
* Plasma SPARC levels were higher in melanoma patients than normal controls (mean 300 ng/ml, n=321 from 76 pts; versus mean 153 ng/ml, n=50 from 50 pts)
* For the high-risk versus low-risk groups respectively, median PFS increased from 3.7 to 6.6 months and median OS increased from 9.4 to 17.7 months
III. Oblimersen one-hour IV infusion in combination with temozolomide and albumin-bound paclitaxel in patients with advanced melanoma (Abstract #8561)
In this ongoing Phase 2 study, 13 chemotherapy-na´ve advanced melanoma patients with an ECOG PS of 0-2 and baseline LDH greater than or equal to 1.1 x ULN have been treated. Therapy consisted of a 30-minute IV infusion of nab-paclitaxel (175 mg/m2) (days 4, 25), oral temozolomide (75 mg/m2) (days 1-42) and a 1-hour IV infusion of oblimersen (900 mg) (days 1, 4, 8, 11, 22, 25, 29, 32) on a 56-day cycle. The primary endpoint for this study is safety and efficacy, with responses evaluated based on RECIST criteria. Results included:
* Three patients who progressed after one cycle
* Ten patients who are continuing treatment; one has demonstrated complete response, four have demonstrated partial response (PR), four have stable disease (SD), and one has yet to be evaluated for response
** One patient with a PR demonstrated increased intra-tumoral caspase 3 and decreased Bcl-2 on day 4 due to an overall reduction in tumor burden, which correlated with a decrease in shed collagen epitopes and clinical response
Non-hematological toxicities were generally mild with one patient hospitalized for drainage of a pre-existing pleural effusion (grade 3), for which she had declined treatment prior to enrollment. No other Grade 3 or 4 events have occurred. Planned enrollment of 14 patients is continuing.
The results from these studies have not been formally reviewed by the Food and Drug Administration.
About nab«-Driven Chemotherapy
Abraxis BioScience has developed a proprietary nanoparticle albumin-bound (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.
The statements contained in this press release that are not purely historical are forward-looking 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 forward-looking statements. These factors include, without limitation, the fact that results from pre-clinical 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 parties. 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.
i American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society; 2009. Available at www.cancer.org/docroot/STT/STT_0.asp
About Abraxis BioScience
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.
ABRAXANE is a solvent-free chemotherapy treatment option for metastatic breast cancer which was developed using Abraxis BioScience's proprietary nab« technology platform. This protein-bound chemotherapy agent combines paclitaxel with albumin, a naturally-occurring human protein. By wrapping the albumin around the active drug, ABRAXANE can be administered to patients at higher doses, delivering higher concentrations of paclitaxel to the tumor site than solvent-based paclitaxel. 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-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.
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Abraxis BioScience, Inc.
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