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ORTHO GETS FIRST FDA OKAY FOR THERAPEUTIC MONOCLONAL: ORTHOCLONE OKT3 APPROVED FOR RENAL TRANSPLANTS, TARGET POPULATION OF 4,000 PER YEAR

Executive Summary

Ortho's Orthoclone OKT3 has an initial approved indication patient population of about 4,000 patients per year. The monoclonal product was approved by FDA on June 19 for "the treatment of acute allograft rejection in renal transplant patients." The 4,000-patient yearly estimate is based on HHS estimates of the total annual kidney transplant population (7,000) and the frequency of allograft rejection. In a statement on the approval of Ortho's treatment monoclonal, HHS said that "in about 60% of these transplants there is a rejection serious enough to require treatment by suppressing the body's immune system." Orthoclone OKT3 would reduce the amount of high dose steroid treatment if it is adopted by the medical community for the approved indication. With an initial target population of 4,000, the Ortho monoclonal could have greater immediate usage than alpha interferon, the other major biotechnology product approved by FDA earlier in June. At a June 19 press conference to announce the product approval, FDA Com. Young indicated a potentially larger use for the Ortho monoclonal in other forms of organ transplantation. Young was asked if Orthoclone OKT3 could be used in all organ transplant cases. The FDA commissioner noted that "theoretically that is true . . . and that is why this is exciting." Young noted, however, that approval applications for other transplants have not yet been reviewed by FDA. "I must emphasize," Young said, "that until we have controlled clinical data it is not appropriate" to use the product in accute rejection cases with other organs. The monoclonal is reportedly being used in early testing for other organ transplants. For example, the drug is being studied in a controlled pilot study at the University of Utah for prophylactic use to prevent rejections in heart transplants. Similarly, a liver transplant prophylactic study is being planned by three Boston groups (Massachusetts General, New England Deaconess, and New England Medical Center Hospital). The Boston groups are already conduting a liver treatment study. Ortho is planning further investigations of the prophylactic use of Orthoclone OKT3 in renal transplants. Commenting on the significance of the approval, the director of the Blood Products Division of FDA's Center of Drugs and Biologics, Thomas Zuck, MD, said Orhtoclone represents an important scientific step because "first of all, it's the first monoclonal and it's of animal origin in terms of cell line, and what it has permitted us to look at is safety and efficacy of a monoclonal made in an animal cell line for a specific therapeutic purpose." FDAer Zuck added that Orthoclone data "has proven that we can take a cell with a specific receptor, in this case a CD3, and we can target an antibody against one antigen on cells." The significance of that discovery, Zuck commented, is "that long term we may be able to selectively look at a receptor on many, many different kinds of cells, and regulate the immune system in some very, very exciting way." Orthoclone was approved after a 27-month review by FDA. The product has previously been approved in France and Switzerland. Highlighting FDA's involvement in the commercialization of biotech products, HHS Secretary Bowen stated in the approval press release that "like interferon, [Orthoclone] is a pioneer therapeutic product of our new world of biotechnology." The HHS release adds that Orthoclone "is the fourth therapeutic product of biotechnology to be approved by FDA. In addition to interferon, the other products are Lilly's Humulin (human insulin) and Genentech's Protropin (human growth hormone). Ortho Pharmaceutical received the first FDA approval for a therapuetic monoclonal approximately five years after Ortho Diagnostics was the first to get an FDA clearance for a monoclonal diagnostic. In May 1981, Ortho Diagnostics received clearance from FDA for Bioclone, a monoclonal version of Anti-C3d for the diagnosis of autimmune hemolytic anemia. Ortho noted in introductory press release material that it "introduced the first monoclonal antibodies for research diagnostic use in 1980." The company added that it "holds patents on ten different monoclonal antibodies and five biotechnology-derived products in various stages of clinical testing." Launch By End Of June: Product Could Be A $12 Mil. Drug Based On Estimated Population The company also pointed out that it is working with Sloan-Kettering Cancer Institute and the Scripps Research Foundation "on a number of promising projects, particularly in the area of cancer-specific monoclonal antibodies." Overall, Ortho's parent Johnson & Johnson reports having completed 10 licensing arrangements with outside firms for biotechnology products during the last five years. In the drug area, for example, the firm is working with Amgen on erythropoietin for chronic anemia ("The Pink Sheet" Feb. 17, pg. 13) and with Chiron on epidermal growth factor for wound healing products ("The Pink Sheet" Feb. 3, p. 8). Orthoclone will be launched by the end of June by the Biotech Div. of Ortho Pharmaceutical. The Biotech Div. was formed in January of this year; it has a staff of 150 to cordinate R&D and regulatory filings and for marketing. Ortho will detail organ transplant centers and will deliver the drug directly to transplant centers. The product has a short half-life. The drug is supplied in 5 mg ampules for bolus injection. The recommended course of therapy is 5 mg/day for 10-to-14 days. The company says that the cost of Orthoclone will be approximately $300 for a 5 mg. ampule, or $3,000 to $4,000 for the entire treatment period. With an estimated patient population of 4,000, Orthoclone could be a $12 mil.-$16 mil. year drug for the kidney transplant use alone. HHS did not address the costs of the drug compared to reinitiation of dialysis or a second implant. From that perspective, the drug could represent another test case of the cost effectiveness of drug therapy vs. other treatment technologies. HHS, however, noted that "the new treatment should reverse many acute kidney transplant rejections and presumably reduce the need for subsequent surgical procedures." Ortho's Orthoclone product license application was based on two clinical trials: one comparing the efficacy of the monoclonal to conventional steroid therapy in patients with acute kidney transplant rejection; and the other assessing the efficacy of the product in patients "for whom conventional methods of treatment had failed or were contraindicated." The second trials were conducted under a compassionate IND. The acute transplant rejection study involved 123 patients in 11 centers. The study found "that the drug reversed the initial rejection episode of the transplanted kidneys 94% of the time, a significant increase over the 75% achieved with treatment by conventional therapies," Ortho said. In the compassionate IND study, "the drug successfully reversed kidney rejection in 65%" of the patients. Commenting on the safety profile of the drug, Doug Norman, MD, associate professor of medicine at Oregon Health Sciences University, said that "the high doses of steroids that are currently used to fight rejection can have serious side effects. That's why Orthoclone OKT3 is so important. It reverses acute rejection -- but doesn't suppress the entire immune system in the process." The release adds that "the initial doses of orthoclone OKT3 may produce flu-like symptoms such as fever, chills, or -- less frequently -- nausea, vomiting or tremors. However, those symptoms generally do not occur with later doses."

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