WASHINGTON _ Although the FDA approved only a handful ofhigh-profile biotechnology products 1994, the agency was awhirlwind of activity. Regulators reduced the overdue applicationbacklog by 90 percent, proposed extensive new adverse eventreporting regulations, formalized the review process for geneticallyengineered whole foods and launched internal efforts to overhaul theagency's clinical and statistical review practices.
As always, FDA actions had a powerful impact on the biotechnologyindustry. Although companies developing therapeutic drugs endureda string of clinical trial disappointments and disasters in 1994,companies developing agricultural products truly had something tocheer about.
In therapeutic drug development, the major regulatory victories ofthe year were won by established biotechnology companies. Formost firms, product disappointments in 1994 came not from the FDAbut rather from the knowledge that clinical and statistical resultsachieved in studies would never pass muster at the agency.
According to BioWorld's records, the FDA approved just two trulynovel biologic therapeutics in 1994: Centocor Inc.'s ReoPro, an anti-blood clotting agent (to be marketed by Eli Lilly & Co.), and EnzonInc.'s Oncaspar, a treatment for acute lymphoblastic leukemia (to bemarketed by Rhone-Poulenc Rorer Inc.) Genzyme Corp. wonapproval for a second generation product, Cerezyme, a recombinantversion of its already-approved Gaucher's disease drug, Ceredase.
Genentech Inc. and Amgen Inc. both won expanded indications forexisting blockbuster products: Genentech's second generation humangrowth hormone product, Nutropin, can be sold to treat children withgrowth failure due to inadequate levels of natural hormone andAmgen's Neupogen (recombinant granulocyte-colony stimulatingfactor) can be sold to accelerate neutrophil recovery in cancerpatients receiving bone marrow transplants.
In 1994, the FDA rejected the synthetic carbohydrate drug,Therafectin, developed by tiny Greenwich Pharmaceuticals Inc. as atreatment for rheumatoid arthritis and the diagnostic imaging agent,ImmuRAID-CEA, developed by Immunomedics Inc.
FDA advisory committees made several recommendations in 1994that the agency has not yet acted upon formally, including: approvalof Univax Biologics Inc.'s WinRho SD, a drug to treat immunethrombocytopenic purpura and prevent Rh immunization; approvalof a new dosing regimen for Genentech's clot-buster drug, t-PA(tissue plasminogen activator); and rejection of U.S. Bioscience'sEthyol, a drug developed to protect against certain toxicities ofchemotherapy in ovarian cancer patients.
In the diagnostic arena, the FDA approved the first ultrasoundcontrast imaging agent, Molecular Biosystems Inc.'s Albunex, fordiagnosis of heart disease. The agent will be marketed in the U.S.under an agreement with Mallinckrodt Group Inc. In addition,BioWorld's records indicate that in 1994, the agency approved atleast nine other diagnostic tests, imaging agents and DNA probeassays developed by biotechnology companies.
In 1994 biotechnology companies filed about 40 investigational newdrug applications, six new drug applications, seven premarketapproval applications (for class 3 devices) and one product licenseapplication.
David Holveck, president and CEO of Centocor, told BioWorld thatthe FDA took a mere 12 months to review and approve ReoPro,evidence of the agency's commitment to "the more innovativeproducts." Holveck said that his company _ which experienced adisappointment when its first major drug for sepsis, Centoxin, failedto gain FDA approval _ has learned from its experiences.
"We've learned that the absolute objectivity and integrity of theapplication, the total package, is paramount to the FDA," saidHolveck.
Holveck said that the comprehensiveness of the FDA review processnow requires massive resources and expertise, resources that smallcompanies strapped for cash will have a "very, very tough time"finding.
Floodgates Opened For Ag-Bio In 1994
For agricultural biotechnology, 1994 will be remembered as the yearthe floodgates were opened. Last May, after four years or review anddeliberations, the FDA's Center for Food Safety and Nutrition(CFSAN) ruled that Calgene Inc.'s genetically engineered Flavr Savrtomato was safe. Shortly thereafter, Calgene won FDA approval(which it had sought voluntarily) for the Flavr Savr as a whole foodand for the kanamycin resistance gene as a food additive.
Five months later, CFSAN scientists completed their "consultationprocess" with companies on seven other genetically engineered foodproducts, concluding that there were no outstanding scientific orsafety concerns. The companies did not apply for or receive formalFDA approval. The products and foods cleared by the FDA inNovember included: a delayed-ripening tomato, a beetle-resistantpotato and a pesticide-resistant soybean plant, all developed byMonsanto Co.; a delayed-ripening tomato from DNA PlantTechnologies Corp.; a tomato from Zeneca Plant Sciences; aherbicide-resistant cotton plant developed by Calgene; and a virus-resistant yellow crookneck squash from Asgrow Seed Co., asubsidiary of The Upjohn Co.
"When we go from taking four years to approve one product toapproving seven products in a single day, we're talking about morethan a watershed year for ag-bio, we're talking about a tsunami,"Calgene CEO Roger Salquist told BioWorld. "In 1994, the processfor approval of genetically engineered foods was clearly defined andmade predictable."
In addition to regulatory actions, the FDA proposed major new rulesfor adverse event reporting in 1994 that have already been criticizedas overly burdensome. (See BioWorld Today, Oct. 31, 1994, p. 1.)The rules, a response to the fialuridine Phase II clinical trial tragedythat killed five hepatitis B patients in 1993, are currently undergoingpublic comment.
The agency also began a rewrite of the general regulations forbiologics in 1994. The overhaul and update of existing regulations isplanned as a massive effort to bring the agency's review proceduresup to "the state of the art" quality and will involve at least onepublic meeting to encourage industry participation at an early stage.n
-- Lisa Piercey Washington Editor
(c) 1997 American Health Consultants. All rights reserved.