Nab-paclitaxel in combination with carboplatin enhanced ORR by 31%.

Abraxis BioScience reports that Abraxane improved overall response rate (ORR) in non-small-cell lung cancer (NSCLC) patients when given as a first-line treatment along with carboplatin. When compared to Taxol plus carboplatin in Phase III, the drug showed a statistically significant 31% ORR increase, according to data being presented at ASCO today.

The company notes that FDA stipulated that demonstrating a statistically superior response rate with an acceptable safety profile would be sufficient to submit an sNDA for this setting. Abraxane, nanoparticle albumin bound (nab®) driven paclitaxel, is approved to treat metastatic breast cancer. The primary endpoint for this trial was complete response (CR) and partial response (PR), while the secondary endpoint was progression-free survival.

In the Phase III NSCLC study, PR or CR was demonstrated in 170 patients (33%) receiving Abraxane versus demonstrated response in 132 patients (25%) treated with the paclitaxel combination, while patients receiving Taxol had an ORR of 25%. In addition, analysis of the squamous cell carcinoma subset, showed a 67% improvement in those who received Abraxane versus those who received Taxol. This finding may be related to the aberrant caveolin-1 overexpression in squamous cell carcinoma, explains Patrick Soon-Shiong, M.D., executive chairman and founder.

The safety results were generally consistent with the known safety profile of Abraxane. The most common grade 3 and 4 adverse events that occurred were neutropenia (45%), anemia (27%), leucopenia (22%), and thrompocytopenia (17%). There was reportedly significantly less sensory neuropathy in the Abraxane versus the paclitaxel groups (3% versus 10%). 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.

Trial design was such that 1,052 patients with histologically or cytologically confirmed stage IIIB or IV NSCLC who had not received prior treatment for metastatic disease were randomized 1:1 to receive six cycles of carboplatin AUC 6 on day one of a three-week treatment cycle in combination with either nab-paclitaxel (100 mg/m2) weekly or solvent-based paclitaxel (200 mg/m2) every three weeks until disease progression or unacceptable toxicity.

Abraxane combines paclitaxel with albumin, a naturally occurring human blood protein. Its proposed mechanism of delivery 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, which is 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.

Abraxane is currently in various stages of investigation for the treatment of non-small-cell lung, malignant melanoma, pancreatic, and gastric cancers. It is also being evaluated in various metastatic breast cancer settings.

The drug won FDA approval 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.

Total revenue from the sales of Abraxane for 2009 grew $15.3 million, or 5.1%, to $314.5 million from $299.3 during 2008. Abraxis attributes this growth to incremental revenue from the continued global expansion into China, Australia, and European markets as well as a higher average net selling price in the U.S. In January 2009, the company re-acquired the exclusive rights to market Abraxane in the U.S. from AstraZeneca.

Later that month it further refined its focus on Abraxane through the spin-out of Abraxis Health. While Abraxis BioScience retained rights to the nab platform, Abraxis Health obtained assets and liabilities related to drug discovery and pilot manufacturing operations as well as development programs other than those with Abraxane. This includes early- and mid-stage studies for Coroxane in cardiovascular indications.

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