Abraxis BioScience, Inc. (NASDAQ:ABII) announced today that findings from a phase 1 randomized trial demonstrated that the n anoparticle a lbumin b ound ( nab ®) driven chemotherapy, nab-paclitaxel (ABRAXANE ® for Injectable Suspension; paclitaxel albumin protein-bound particles for injectable suspension) is well-tolerated and active in the second-line treatment of high-grade, non-muscle-invasive bladder cancer that has been refractory to standard intra-bladder infusion (intravesical) therapy. The results from a dose escalation trial of infusion of ABRAXANE directly into the bladder in these patients who have failed standard chemotherapy are being presented for the first time as a late-breaker during an oral session on June 1 st at the 2010 American Urological Association Annual Meeting in San Francisco.
Non-muscle-invasive bladder cancer is difficult to treat and up to 50 percent of patients receiving drugs infused into the bladder (intravesical agents) will experience recurrence of the cancer. Typical second-line treatment for patients with high-grade, non-muscle-invasive bladder cancer who have failed standard intravesical therapy is surgical removal of the entire bladder, cystectomy. The American Cancer Society estimates that approximately 70,980 people were diagnosed with bladder cancer in the United States in 2009, and that approximately 18,170 died from the disease. i The prevalence of bladder cancer in the United States exceeds 500,000 people. ii
In this study of 18 patients who previously failed treatment with Bacillus Calmette-Guerin (BCG), patients were randomized to receive six weekly intravesicular-instillations of nab-paclitaxel beginning at a dose of 150 mg, with a dose escalation model used until a maximal deliverable dose (MDD) was identified. The drug was well-tolerated with no grade 2, 3 or 4 drug related local toxicities encountered and with 12 out of 18 patients (56 percent) experiencing only grade 1 local toxicities, dysuria being the most common. After 108 intravesical instillations, no systemic toxicities occurred. In addition, there was no systemic absorption of nab-paclitaxel up through the 375 mg dose. A preliminary examination of response rate found that five out of 18 patients (28 percent) demonstrated a complete response with nab-paclitaxel after 12 weeks in these patients who had failed BCG therapy.
“The preliminary results of this study suggest nab-paclitaxel may have a potential benefit for high-risk non-muscle-invasive bladder cancer patients who have failed prior intravesical treatment or who are unable or unwilling to undergo cystectomy,” said James McKiernan, M.D., Director of Urologic Oncology, Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University. Enrollment is ongoing for a phase 2 trial evaluating nab-paclitaxel for refractory non-muscle-invasive bladder cancer at the MDD.“The promising results of ABRAXANE in the treatment of patients with bladder cancer support the efficacy of nab-driven chemotherapy across an increasing range of advanced and difficult-to-treat cancers,” said Patrick Soon-Shiong, M.D., Executive Chairman and founder of Abraxis BioScience. “This study further supports our commitment to develop a deeper understanding of how albumin-bound ABRAXANE’s unique affinity for the secreted protein SPARC may enable targeted cytoxotic agents to be delivered directly into the tumor microenvironment, supporting better patient outcomes.” ABRAXANE is currently approved 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. ABRAXANE has also been granted orphan drug designation by the Food and Drug Administration for the treatment of pancreatic cancer as well as stage IIB-IV melanoma.