Drug decisions upset biotech community An FDA advisory committee's decision to not recommend approval of two drugs sent tremors through the b i o t e c h n o l o g y community last week. Amid high expectations about new biotechnology drugs coming of age, the committee's decision to not clear two of the four up for approval disappointed and surprised many in the industry and led to falling stock prices for the unsuccessful applicants. At an approval rate of only a few per year, only 11 biotechnology drugs have been approved since 1986. The industry and investors have been growing anxious, with dozens of drugs now in various stages of clinical trials or with applications pending. Already well established with profitable products on the market, the decision allowed Genentech and Schering-Plough to come out even further ahead. The Biological Response Modifiers Advisory Committee recommended approval for Genentech's 7-interferon for treating chronic granulomatous disease, a rare, inherited immune-related disorder. And, Schering-Plough's a-interferon, which has been approved for treatment in three other diseases, got a positive vote for use in certain forms of hepatitis. Cetus and Immunex, two smaller biotechnology companies that have yet to market their first proprietary drug products in the U.S., did not receive favorable recommendations. In both cases, the committee asked for additional information and further analysis of data from drug trials. Having just filed in February, comments Alan Frazier, Immunex's chief financial officer, the company was delighted to be up for approval with its granulocyte macrophagecolony stimulating factor (GM-CSF) for use in treating graft failure in bone marrow transplant patients. Because of its apparent benefit and limited toxicity, the committee has recommended FDA allow Immunex, and its licensee Hoechst-Roussel, to make the drug available to patients while review continues. Immunex is
expected to be able to satisfy the request with data from ongoing trials by November, when the committee is next scheduled to meet. Cetus has been asked to look into data from trials on interleukin-2 (IL2) in the treatment of metastatic renal cell carcinoma to determine which patients may be expected to respond. As the only available treatment, IL-2 shows some benefit in up to 20% of patients treated but has rather severe, yet reversible, side effects, says Robert A. Fildes, president and chief executive officer of Cetus. Whereas a license was filed with FDA about two years ago, Cetus' IL-2 product has been approved in nine European countries. Fildes says he was "surprised and disappointed" that the recommendation did not come through, in light of what he sees as ample evidence of
the drug's effectiveness and of its presenting no greater danger than many chemotherapeutic drugs. The company has been working on the product for about eight years and has invested in excess of $100 million. Both Cetus and Immunex have been building up manufacturing, sales, and marketing capabilities in anticipation of launching new products, while reporting losses in 1989 of nearly $50 million and just over $14 million, respectively. The announcement of the committee's findings caused Cetus' stock prices to drop $5*6 to $10 3 i and Immunex's to fall $4.00 to $27. Amgen and Genetics Institute, two other biotechnology companies that have their own GM-CSF and IL-2 products in the regulatory pipeline, also saw their stock prices drop. Ann Thayer
EPA forced to act on Los Angeles clean air plan The Environmental Protection Agency has proposed an ambitious plan for curbing air pollution in the Los Angeles area, the nation's most polluted. But reluctant agency officials say they are advancing the socalled federal implementation plan for southern California only because a court order has forced EPA to do so. Under the terms of settlement of a lawsuit brought against EPA in 1988 by the Sierra Club and the Coalition for Clean Air, the agency had until July 31 to propose a plan for the Los Angeles basin. The environmental groups sued EPA under a provision of the Clean Air Act that says the federal government must act if regional authorities do not develop an approved plan to clean up their pollution problems. However, says William G. Rosenberg, EPA assistant administrator for air and radiation, state and local authorities in southern California have developed a far-reaching cleanup strategy. But because many of the provisions of the California plan do not yet have the force of law, EPA cannot formally approve it. Furthermore, Rosenberg says, Congress is currently negotiating major amendments to the Clean Air Act that likely will change the law about federal
plans as well as give certain exemptions to Los Angeles. "We don't need EPA to hold the hand of local government in [Los Angeles]," Rosenberg says. "We hope Congress will relieve us of this obligation. We would prefer to have [Los Angeles] work under its own plan under the new bill than have us enforce the old law." Accordingly, EPA's proposal anticipates many of the provisions of the new Clean Air Act and dupli-
Smog controls must make "reasonable progress" % emissions reductions needed 3 100 - ^ S ^ — Reasonable further progress11 ^^v. 80
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a Reductions in emissions of volatile organic compounds required to lower ozone levels to meet federal health standards, b Minimum reductions that California must meet to avoid EPA-imposed control measures, c Likely actual emissions, d Schedule of reductions proposed by California. Source: Environmental Protection Agency
August 6, 1990 C&EN 5
News of the Week cates many of the California plan's sweeping strategies to reduce ozone and carbon monoxide levels. Much of the EPA plan would go into effect only if the Los Angeles area fails to make "reasonable progress" toward meeting federal health standards under the state and local regulations. The largest single source of air pollution in the Los Angeles region is emissions from motor vehicles, so both plans include requirements for cleaner gasoline. Both also would mandate "ultraclean" cars—powered by electricity, natural gas, alcohol fuels, or reformulated gasoline—early in the next century. "We're pretty confident that our local plan will do the job and that [EPA] won't have to implement the federal plan," says Claudia Keith, spokesman for the California South Coast Air Quality Management District. The Sierra Club says it is pleased with the EPA plan for Los Angeles but opposes the proposed amendments to the Clean Air Act that would remove the requirement that EPA implement cleanup plans if states fail to do so. "EPA is like a gorilla in the closet that ensures states will take action," says Daniel Weiss, director of the Sierra Club's environmental quality program. "Unfortunately, proposals in Congress would turn the gorilla into a monkey. They would leave cleanup to the states, and history has shown us they don't have the muscle to do it." Pamela Zurer
Farm bills forbid export of banned pesticides There are major differences between the recently approved Senate and House versions of the 1990 five-year reauthorization of the nation's agricultural programs. But these differences don't extend to provisions on pesticide export, agricultural research, and sustainable farming. For example, the Senate bill, S. 2830, passed on July 27, contains provisions designed to break the socalled circle of poison in which pesticides banned in the U.S. are exported for use in other countries and return to the U.S. in the form of residues on food. 6
August 6, 1990 C&EN
Those provisions, strongly championed by Agriculture, Nutrition & Forestry Committee chairman Patrick J. Leahy (D.-Vt.), would prohibit the export of any pesticide that either has been banned or does not have a food tolerance (an allowable residue) level in the U.S. The bill also would require the Environmental Protection Agency Administrator to cancel or suspend a pesticide's food tolerance at the same time its registration is canceled or suspended for dietary reasons. S. 2830 would make several other changes in pesticide export requirements, including establishment of procedures providing foreign governments an opportunity to make an informed decision regarding the import of a pesticide whose use is restricted in the U.S., and to refuse that import if they so wish. It would also require that labels on an exported pesticide contain the same information as the U.S. label, and that the label be written in the official language of the country of use.
The House bill, H.R. 3950, contained no such provision when it was reported out by the Agriculture Committee. However, an amendment offered by Rep. Mike Synar (D.-Okla.) to add export provisions to H.R. 3950 similar to those contained in the Senate bill was approved during the House floor debate on the agriculture bill. Both bills also contain provisions, with minor variations, aimed at fostering research and education on sustainable agriculture technologies and practices; authorizing a major, $500 million expansion of the U.S. Department of Agriculture's competitive research grants program; establishing a new minority research fellowship effort; and defining precisely what foods can and cannot be labeled "organic." House and Senate conferees will begin negotiating a compromise version of the farm bill after Congress returns from its month long August recess. Janice Long
Public concern exceeds action on environment A major public opinion poll finds that U.S. residents are very aware of the country's environmental problems, but most aren't doing anything about them. The poll did find that income, education, and gender correlate most strongly with environmental concern and behavior. The poll was commissioned by S. C. Johnson & Son, manufacturers of a large variety of consumer products. It was performed by Roper Organization of New York. Only 22% of those surveyed are actively working toward environmental solutions, notes Burns Roper, chairman of Roper Organization. But 78% of Americans say major efforts are needed to improve the environment. "This shows a fairly large gap between popular attitudes and daily behavior," he adds. The public puts the blame for environmental problems on several groups, but pollution by manufacturers ranks highest. The public thinks the environmental laws could be enforced better. Industrial plant emissions are considered the worst air pollution problem, while
industrial discharges are seen as the worst water pollution problem. But the worst solid waste problem is perceived to be disposable diapers. Many (13%) also see aerosols as a problem, believing chlorofluorocarbons are still widely used in them. In general, the poll finds that the most environmentally active people are women (twice as many as men), highly educated (twice as many with college degrees), who earn relatively high incomes. The public overwhelmingly gets its information on environmental issues from television and newspapers. Major corporations are ranked last as major sources of information. In fact, the poll shows the public seeks more government regulation of business. Jane Hutterly, director of environmental actions for S. C. Johnson & Son, says, "It is clear . . . that a significant education effort on the real causes affecting the environment is needed. Otherwise, it is very likely that the public policymakers will make decisions driven by inaccurate perceptions rather than reality." David Hanson
