TAXOL RAW MATERIAL: BRISTOL ACHIEVES FOUR-WAY AGREEMENT

TAXOL RAW MATERIAL: BRISTOL ACHIEVES FOUR-WAY AGREEMENT with the government but may face a further review by Rep. Wyden (D- Ore.). On June 18, Bristol-Myers Squibb concluded agreements for cutting rights to Pacific yew trees on government lands, with the Agriculture Department and Bureau of Land Management. Those agreements supplement an earlier development agreement for the anticancer compound with the National Cancer Institute. Together, the agreements constitute an unusual package of interrelated projects to permit the commercialization of the compound. In return for the right to cut on government lands, Bristol-Myers is providing funding for USDA and BLM to conduct inventories of Pacific yew, to conduct research on the ecology, silviculture, and management of the Pacific yew, and to support all phases of bark collection and delivery. Current estimates are that Pacific yew trees grow on 3 mil. acres of land under BLM's purview and on 9 mil. acres of Forest Service-controlled land. Wyden, who represents a state in the thick of the current forest-cutting debates, is raising environmental and drug development questions about the agreements. Wyden indicates he may hold a hearing on the agreements in late July before the House Small Business/Regulation Subcommittee. In a June 17 letter addressed to USDA Assistant Secretary James Moseley, Wyden raised four issues. He stated: "First and foremost, I want to make sure that we've got appropriate planning in place to make [the] best use of this rare tree. Secondly, I want to make sure that we guarantee survival of the species. Thirdly, I want to make sure that Bristol-Myers Squibb pays a fair price in return for their exclusive rights. And finally, I must be convinced that these agreements give the American public its best shot at getting an important, new anti-cancer drug." Wyden also raised the exclusive rights issue. He added "once these priorities are met, I am also concerned that small drug manufacturers have equitable access to the Pacific yew." At the June 19 signing, Bristol-Myers Squibb VP-Licensing Z. P. Horovitz noted that under the terms of the CRADA [cooperative research and development agreement] signed last January with NCI, Bristol-Myers' two major commitments are to provide taxol for NCI and researchers to conduct clinical trials, and to compile the resulting data for an NDA. "Our obligation to do this relates to doing it with minimal effects on the environment," he said. Horovitz stated that under the terms of the CRADA, "we will have some limited exclusivity in the marketplace, just based on filing for -- if we get approval -- for the new drug application. That is five years. We also have filed for ovarian cancer for orphan drug status, which could give us seven years of exclusivity." He added, however, that Bristol-Myers would withdraw the orphan drug application if "indeed we find other indications and the population expands." As of April 15, NCI's CRADA with Bristol-Myers was one of 25 ongoing, effective collaborations that the institute has negotiated. Throughout NIH, there are 90 active CRADAS. In addition, FDA has approved two; the Alcohol, Drug Abuse and Mental Health Administration has 12 and the Centers for Disease Control has 16. Regarding immediate plans for Pacific yew harvesting, Associate Forest Service Chief George Leonard stated June 19 that "we have no plans this year to enter into the habitat conservation areas. If we find as we go out two or three years that this is desirable, the only entry into the habitat conservation area would be that which is agreed upon through consultation with the Fish and Wildlife Service and [Northern] spotted owl experts." The spotted owl, which has been declared a threatened species, lives in old-growth forests in the Northwest, where Pacific yews grow. According to NCI, 750,000 pounds of yew bark from 38,000 trees will be needed this year to produce enough taxol for clinical trials. That amount of bark produces 25 kilograms of taxol, or enough to treat about 12,500 cancer patients. As of early May, Bristol-Myers had collected about 25% of its target goal. Under the CRADA, Bristol-Myers has committed to provide one kg of taxol for compassionate use this year.