SILVER SPRING, MarylandThe Oncologic Drugs Advisory Committee (ODAC) has recommended that FDA work with Abraxis Bioscience to design a well-controlled, randomized, reasonably sized clinical trial of Abraxane-paclitaxel protein-bound particles for injectable suspension (albumin bound)to support a future supplemental application for the drug as an alternative to standard paclitaxel (Taxol) in the adjuvant treatment of node-positive breast cancer.
The panel's 13-to-1 vote rejected the company's contention that no additional efficacy study should be required and upheld the FDA's contention that it needs the trial to support the efficacy and safety of Abraxane in this indication. The panel urged the agency and sponsor to collaborate in determining a suitable and reasonably sized patient population to provide the answers. "We intend to move as quickly as possible to discuss the next steps with FDA," said Michael J. Hawkins, MD, Abraxis' chief medical officer.
Abraxane is the first of a new class of protein-bound taxanes that uses albumin, a natural carrier of water-insoluble molecules, to transport the active drug (paclitaxel). Abraxane was developed to eliminate the hypersensitivity reactions induced by Cremophor, which serves as the paclitaxel carrier in Taxol. Abraxane won initial FDA approval in January 2005 for use after failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy.
Abraxis sought approval for the drug as an adjuvant therapy through a seldom used regulatory route known as Section 505(b)(2). Typically, drug sponsors support their applications with their own studies. However, 505(b)(2) applies to new formulations of existing drugs and allows FDA, "where appropriate," to base its approval entirely or partially on studies that the applicant did not conduct and for which it has not a obtained a right of use.
Taxol is approved for adjuvant use in node-positive breast cancer. In seeking supplemental approval of Abraxane under Section 505(b)(2), Abraxis wanted to use data from the preclinical genetic toxicology studies and the clinical trial submitted to FDA to support the approval of Taxol for adjuvant use, as well as the phase III trial it conducted comparing the two drugs in metastatic breast cancer, which served as the basis for the 2005 approval of Abraxane. Abraxis said it would willingly conduct a safety study of Abraxane as adjuvant therapy but saw no need for an efficacy trial.
Abraxane's formulation allows it to deliver a higher dose of paclitaxel than Taxol because it contains no Cremophor, and studies have shown that Abraxane has greater antitumor power in metastatic breast cancer than the older drug, Dr. Hawkins noted. "Therefore, there is no scientific basis to hypothesize that Abraxane will be less effective than Taxol as adjuvant therapy," he said.
FDA's medical review team challenged this assertion. For one thing, the use of albumin instead of Cremophor in Abraxane results in pharmacokinetics different from Taxol, said FDA pharmacologist Brian Booth, PhD.