Providing new hope for breast cancer patients, Abraxane soon will offer the antitumor benefits, without the toxic solvent side effects, of paclitaxel.

The FDA approved the product developed by American Bioscience Inc., of Santa Monica, Calif. It will be manufactured and marketed through the company's 70 percent-owned subsidiary American Pharmaceutical Partners Inc. (APP), of Schaumburg, Ill.

"What this means to the breast cancer patient and to the physician is they can now provide the full potential of this drug paclitaxel," said Patrick Soon-Shiong, chairman, president and CEO of privately held American Bioscience and executive chairman of APP.

APP's stock (NASDAQ:APPX) soared 28.4 percent, or $11.01, on Monday to close at $49.72.

Abraxane is indicated to treat breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. With the approval, the FDA has designated a new group of protein-bound particle drugs in which Abraxane is the first in the class. The product consists of albumin-bound paclitaxel nanoparticles, which are one-hundredth the size of a single red blood cell.

"What is exciting now about Abraxane is it is the first of a new class of drug products, and second, it is the first taxane that is free of solvent," Soon-Shiong told BioWorld Today. "As a result, it can be given without premedication and without a black box warning of severe hypersensitivity reactions.

"It can be given at a 50 percent higher dose of chemotherapy," he said, "and the outcome is an almost doubling of the response rate when compared to Taxol."

Another benefit of Abraxane: It is infused over 30 minutes, compared to the three hours required for Taxol, Soon-Shiong said.

The approval is a significant milestone for APP, said analyst Steven Gerber, of Los Angeles-based Wedbush Morgan Securities.

He believes the product, APP's first proprietary approval, will double the company's sales and profit levels. APP, which has gained several approvals for generic drugs, has annual revenues of about $400 million.

"We think this could be a $500 million product for them within three years," Gerber told BioWorld Today.

The approval triggered a $15 million milestone payment from APP to American Bioscience. The companies have a 50/50 revenue-sharing agreement.

"This is not a cure for cancer. This is not a revolutionary new treatment," Gerber said, "but in our view, it's a substantial improvement in a valuable, but very flawed, treatment option, which is paclitaxel."

With Taxol, paclitaxel is dissolved in the solvent Cremophor-EL and delivered intravenously. Another cancer drug, Taxotere (Sanofi-Aventis Group) consists of docetaxel dissolved in the solvent Tween 80. In addition to causing neutropenia and other allergic reactions, solvents can leach plasticizers from the standard IV tubing. They also might minimize antitumor activity by trapping the active compound in the bloodstream.

Toxicities caused by solvents include hypersensitivity reactions, severe myelosuppression and prolonged peripheral neuropathy, such as severe edema. While paclitaxel has long been the most effective cancer compound ever discovered, it has been limited by its need for solvents.

American Biosciences has kept a relatively low profile since its 1994 founding, but the company is ready to tell its story, Soon-Shiong said, highlighting how its nanoparticle albumin-bound (NAB) technology can lead to drugs like Abraxane. NAB taps into the albumin protein, which carries hydrophobic nutrients, vitamins, steroids and other compounds. Albumin regulates the delivery of essential molecules across the blood vessel wall into tissues by activating albumin receptors on blood vessels. The technology binds water-insoluble compounds with albumin in a nanoparticle state through a manufacturing process that retains the full biological properties of albumin. That allows for a product to be readily bioavailable once it is administered to patients.

"This, we believe, could change how we deliver cancer chemotherapy drugs," Soon-Shiong said. "The exciting opportunity is we've discovered that albumin recognizes a receptor on the vessel wall called gp60."

When the albumin-bound nutrient docks with gp60, it triggers the formation of a sac, which then is transported from the blood vessel wall to the underlying tumor tissue.

Tumors associated with a variety of cancers also secrete a specific protein called SPARC, which binds to albumin. That knowledge could lead to a variety of applications for American Biosciences' technology in the areas of head and neck cancer, melanoma, prostate cancer, esophageal cancer and others.

"The ubiquitous nature of this biological pathway from the bloodstream across the blood vessel wall to the tumor has never been exploited before," Soon-Shiong said.

APP has hired about 100 experienced sales representatives who will begin marketing Abraxane within the next 45 days.

American Bioscience is conducting clinical trials in China, and it is preparing to file for European approval, as it searches for partners outside of North America.

The companies filed the new drug application for Abraxane last March. The NDA included data from 106 patients in two single-arm, open-label studies, and from a randomized Phase III study comparing Abraxane with New York-based Bristol-Myers Squibb Co.'s Taxol. (See BioWorld Today, March 9, 2004.)

Soon-Shiong said the approval of Abraxane marks the culmination of more than a decade of research in the science of albumin-bound nanoparticles. The company is expanding the technology with other hydrophobic insoluble compounds. It is studying nanoparticle paclitaxel in Phase II trials for the prevention of coronary artery restenosis.

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