ABI 007 [Abraxane™] is an albumin-stabilised nanoparticle formulation of paclitaxel designed to overcome insolubility problems encountered with paclitaxel. This then eliminates the need for toxic solvents like cremophor, which limits the dose of paclitaxel that can be administered and hence affect overall drug efficacy. Studies have shown that the albumin receptor-mediated paclitaxel-transport mechanism is analogous to the opening of a ‘trapdoor’ on the endothelial cell wall within blood vessels. This facilitates the passage of ABI 007 from the bloodstream via the blood vessels to the underlying tumour tissue.[1]ABI 007 is being developed for the treatment of a variety of tumour types by American Pharmaceutical Partners. In addition to the standard infusion formulation of ABI 007, oral and pulmonary delivery formulations are also being investigated.American Pharmaceutical Partners, a subsidiary of American BioScience, secured exclusive North American marketing and manufacturing rights to ABI 007 from American BioScience in November 2001.In anticipation of product launch within the fourth quarter of 2004, the company formed Abraxis Oncology and recruited an experienced sales and marketing team. The company has also accumulated approximately $US28 million of paclitaxel inventory. As such, American Pharmaceutical Partners anticipates pre-launch expenses to cost approximately $US40 million, incurred over 2004. In addition, the company expects to make two milestone payments worth $US10 million as well as $US15 million, based upon US FDA acceptance of NDA filing in the second quarter of 2004 and subsequent US FDA approval, respectively. The milestone for US FDA approval would be capitalised and amortised over the estimated life of the product.[2]Previously, American Pharmaceutical Partners reported that its rolling NDA submission for ABI 007 commenced in May 2003. In July 2003, the company announced that this was progressing on schedule and expected to have completed its entire NDA submission by the end of 2003. The company also began preparations to form a sales and marketing group in anticipation of product launch. In addition, production of commercial quantities of ABI 007 was expected to begin in the second half of 2003. The US FDA granted fast-track status to ABI 007 for this indication in January 2003.[3]The decision for NDA filing was based on the successful completion of a phase III trial evaluating ABI 007 versus standard paclitaxel among 460 patients with metastatic breast cancer in the US.[4,5]In September 2003, American Pharmaceutical Partners and American BioScience jointly announced positive interim results from the trial, which shows that the primary efficacy objective had been exceeded.[6]American BioScience completed this phase III trial in early 2003 with the results unblinded in mid-2003. The phase III study directly compared the efficacy of ABI 007 260 mg/m2versus paclitaxel 175 mg/m2. Both agents were administered every 3 weeks. ABI 007 was administered as a 30-minute infusion without steroid pretreatment. Paclitaxel-treated patients received steroid pretreatment and the drug was administered over 3 hours. Enrolment was completed in December 2002 with 460 first- and second-line metastatic breast cancer patients enrolled. A Data Monitoring Committee concluded in October 2002 that a sample-size adjustment of the phase III trial was not required and that the study could be continued to completion.A phase II trial of ABI 007 was also underway in metastatic breast cancer patients who have failed taxane therapy. The trial was evaluating a weekly rather than 3-weekly regimen of ABI 007.Also in February 2004, American BioScience initiated a multicentre phase II trial in patients with metastatic melanoma. The trial will evaluate both chemotherapy-naive patients (at a dose of 150 mg/m2administered weekly) and patients who have previously received chemotherapy (at a dose of 100 mg/m2administered weekly) as treatment for metastatic disease.[7]In May 2003, American Pharmaceutical Partners reported that ABI 007 is also being evaluated for the treatment of non-small cell lung cancer, ovarian cancer, melanoma and cervical cancers. Phase I/II trials have also been conducted in other solid tumours, including squamous cell cancer of the head and neck, and pelvis. Phase I trials have also been conducted in patients with solid tumours to evaluate the administration of ABI 007 on a weekly schedule.In September 2003, American BioScience was issued US patent No. 6 506 405, which has 89 claims covering compositions of matter and unit dosage forms. In addition, the patent covers methods of use without the requirement for pretreatment with steroid therapy or growth factor support.In July 2003, the US Court of Appeals for the Federal Circuit in Washington DC unanimously ruled that American BioScience is the true and rightful owner of patent No. 5 780 653. This patent covers three next-generation taxane anticancer compounds. This ruling overturned a lower court decision in a lawsuit brought in 1998 by Florida State University (FSU) and FSU Prof. Robert Holton's privately held company, Taxolog. In the lawsuit, FSU and Taxolog alleged that Prof. Holton and others at FSU were the true inventors of the compounds claimed under American BioScience's patent.