Breast cancer patients taking Abraxane in a Phase III trial responded almost twice as well as they did when taking a marketed product - providing American BioScience Inc. and American Pharmaceutical Partners Inc. (APP) the data they needed to file a new drug application.

The companies said Monday that they completed the NDA filing for Abraxane as a treatment for metastatic breast cancer. With fast-track designation and a potential priority review, the companies could receive approval in six months and launch the product in the fourth quarter.

The NDA filing is based on Phase I and II trials, as well as a pivotal, randomized, controlled Phase III trial that compared Abraxane at 260 mg/m2 with Taxol at 175 mg/m2. The higher dose of Abraxane was possible because of its delivery mechanism, which allows more of the active compound to reach patients without added toxicities.

"It's a different way of addressing how we approach cancer chemotherapy," said Patrick Soon-Shiong, chairman, president and CEO of both American BioScience and APP.

Soon-Shiong is a co-inventor of the nanoparticle technology that makes Abraxane unique.

Abraxane combines the active drug paclitaxel with a natural protein called albumin. Using the nanoparticle technology, Abraxane is formed into a nanoparticle one-hundredth the size of a red blood cell, eliminating the need for a solvent.

Soon-Shiong said with Abraxane the target is shifted from the tumor itself to the specific albumin receptor on the blood vessel wall of the tumor neovasculature.

"The albumin locks onto this receptor, and that triggers the pathway," Soon-Shiong told BioWorld Today. "Nobody has really hijacked or used this pathway."

Abraxane initially was developed to address toxicities associated with the solvents Cremophor-EL and alcohol, which are used in Taxol - a product that received approval in December 1992 and was licensed to New York-based Bristol-Myers Squibb Co. from the National Institutes of Health.

"The trouble is these solvents are toxic and they actually inhibit or trap the drug in the plasma blood space," Soon-Shiong said.

The toxicities require patients to be premedicated with corticosteroids and to receive extended infusion times of Taxol. They also limit the dose and demand the need for specialized intravenous tubing sets to avoid leaching of plasticizers into the patients.

In the Phase III trial, Abraxane and Taxol were administered every three weeks in 460 metastatic breast cancer patients. Phase III data released in December showed an almost doubling of the response rate in Abraxane-treated patients, as well as a slower time to tumor progression in first- and second-line patients. The study also showed Abraxane was administered safely over 30 minutes without the need for steroid premedication.

Abraxane also has been found effective in Taxol-refractory patients. The NDA is seeking approval of Abraxane as a second-line therapy.

Privately held American BioScience, of Santa Monica, Calif., developed Abraxane, while its majority-owned APP subsidiary, of Schaumburg, Ill., holds exclusive North American manufacturing and marketing rights. Last fall, APP formed Abraxis Oncology, which includes a 50-person sales force, to prepare for the launch of Abraxane. If the FDA accepts the Abraxane NDA for review, APP is required to make a $10 million milestone payment to American BioScience. Upon final FDA approval, the company would make another $15 million payment.

The company has not yet decided on pricing for the product.

"The market opportunity is relatively large," Soon-Shiong said. "The taxane market is in excess of $1.8 billion in the U.S., and $2.5 billion to $3 billion worldwide."

A research note put out last week by CIBC World Market Corp. analysts Elliot Wilbur and Colleen Lahey stated that the total U.S. taxane market for metastatic breast cancer is about $2 billion, assuming a usage of 40 percent to 45 percent.

"We continue to believe Abraxane has multi-hundred-million-dollar potential," the note stated. "With only 40 percent penetration of the [metastatic breast cancer] setting, we believe Abraxane sales could exceed $300 million."

Hoping to expand Abraxane into other indications, American BioScience is conducting other studies: a Phase I/II study for non-small-cell lung cancer and a Phase II trial in metastatic melanoma. It also is being studied in head and neck cancer.

Soon-Shiong said the companies will file for regulatory approval in other countries this year in the breast cancer indication.

"We think we will probably make a submission in Canada three months from now, and probably submit in Europe three to six months from now," he said.

Taxol is harvested from the bark of the Pacific yew tree, found mainly in old-growth forests in the Pacific Northwest. The product, which is approved for various cancer indications, including ovarian, breast and non-small-cell lung cancer, had about $1.2 billion in worldwide sales in 2002.

In addition to Taxol, Abraxane would compete with Strasbourg, France-based Aventis SA's Taxotere, which generated about $1.2 billion in worldwide sales in 2002.

APP's shares (NASDAQ:APPX) closed unchanged Monday at $38.04.