While drug makers Bristol-Myers Squibb Inc. and Rhone-PoulencRorer Inc. extol the virtues of yew tree-derived taxoids for treatingcancer, a Canadian start-up company has discovered the semi-synthetic compounds have angiogenesis inhibiting properties thatmay be effective against other diseases, such as arthritis.

"We were the first to identify paclitaxel for diseases other thanmalignancies," said Kennith Mellquist, senior vice president ofAngiogeneis Technologies Inc. (Angiotech), of Vancouver, BritishColumbia.

Later this year or in early 1997, Angiotech hopes to take paclitaxel_ the generic name for New York-based Bristol-Myers Squibb'sTaxol _ into the clinic as a treatment for rheumatoid arthritis, adisease that causes inflammation and degeneration of joints andstrikes about 150,000 people a year in the U.S.

Rather than administering the paclitaxel systemically, Angiotechintends to deliver it directly into joints in sustained-release polymericmicrospheres, which will reduce the dose needed and the side effectsseen in Taxol cancer treatments.

The company's preclinical work with paclitaxel suggests it impactsseveral events in the progression of rheumatoid arthritis. It inhibitsangiogenesis, the blood vessel formation needed to sustain the jointdamaging build-up of synovial cells, and prevents production ofdigestive enzymes, such as collagenase, which break down cartilage.The drug also combats proliferation of inflammatory cells.

With Angiotech, founded in 1992, moving from the research stage toclinical development, the board in January 1996 hired Robert Abbott,former head of San Diego-based Viagene Inc., as president and CEO.

Abbott _ also co-founder and former president and CEO of Seattle-based NeoRx Corp. _ was available for the job after the $95 millionbuyout in October 1995 of Viagene, a gene therapy company, byChiron Corp., of Emeryville, Calif.

Viagene's top executives were offered positions with Chiron, butAbbott declined. He and his family wanted to return to the Northwestcoast of the U.S.

Vancouver is less than 150 miles north of Seattle and when Abbottmet with Angiotech's scientific co-founder, William Hunter, theyrendezvoused on Abbott's 50-acre island, which is only a short hopby seaplane from the Canadian city.

"I was involved with two companies that were technology plays,"Abbott said. "It takes huge amounts of money and time to developproducts. Angiotech already is a product play."

He said the company has identified "clear mechanisms related todisease" and has a discovered a new use _ blocking inappropriateangiogenesis _ for a product that already is on the market.

In addition to arthritis, Abbott said, Angiotech is targeting paclitaxelfor neovascular disorders of the eye and other autoimmune diseases.

The rheumatoid arthritis study, he added, is one of three clinical trialsexpected to get under way during the next year.

Early in 1996 in England a trial is slated to begin using paclitaxel in apolymer coating for stents, which are tubular devices that keep openthe throats of esophageal cancer patients. The study will determine ifpaclitaxel, which would be released over months, can prevent tumorcell overgrowth of stents and lengthen the time between replacementof the devices.

In a third study Angiotech will evaluate vanadate as a cancertreatment. The vanadium-based compound is believed to possess cellproliferation and enzyme inhibiting properties similar to those ofpaclitaxel.

Angiotech can develop paclitaxel without compensation to Bristol-Myers because the pharmaceutical firm does not have a compositionof matter patent on Taxol. Rhone-Poulenc Rorer, of Collegeville, Pa.,makes a different version of paclitaxel, called docetaxel, whose brandname is Taxotere. Both Taxol and Taxotere are marketed foradvanced breast cancer.

Angiotech has filed patents in the U.S. covering its uses of paclitaxeland manufacture of the drug with the company's polymeric deliveryvehicles. n

-- Charles Craig

(c) 1997 American Health Consultants. All rights reserved.