FUJISAWA GANITE GALLIUM NITRATE SHIPMENTS BEGAN JAN. 25

FUJISAWA GANITE GALLIUM NITRATE SHIPMENTS BEGAN JAN. 25 eight days after FDA approval of the product for treatment of hypercalcemia in cancer patients. Ganite, an orphan drug, was given a "1B" rating by FDA, designating a new molecular entity offering a modest therapeutic advantage. An NDA for gallium nitrate, originally called Calstat, was filed March 17, 1989 by Lyphomed prior to its acquisition by Fujisawa. Ganite will be marketed to oncologists by Fujisawa's 100- person hospital sales force. Fujisawa has hired about 15 oncology specialists to lead in detailing the product and intends to add about nine more. The price to wholesalers will be $ 80 per vial -- each vial will contain enough product for a five-day infusion. The recommended dose is 200 mg/m/day for five days. The product will be officially unveiled at a Feb. 5 press conference in New York City. Following the recommendation of FDA's Endocrinologic and Metabolic Drugs Advisory Committee, the approved indication restricts the product to use "for the treatment of clearly symptomatic cancer-related hypercalcemia that has not responded to adequate hydration" ("The Pink Sheet" Oct. 16, 1989, T&G-9). The product was reviewed by the FDA advisory committee in October 1989, 14 months prior to approval, Fujisawa estimates a patient population for the drug of between 100,000 and 150,000. Final labeling also reflects the committee's concerns about gallium nitrate's nephrotoxicity: the package insert includes a boxed warning that "concurrent use of gallium nitrate with other potentially nephrotoxic drugs (e.g., aminoglycosides, amphotericin B) may increase the risk for developing severe renal insufficiency in patients with cancer-related hypercalcemia." The warning also advises physicians that "Ganite therapy should be discontinued if the serum creatinine level exceeds 2.5 mg/dL." Additional precautions include recommendations for daily serum calcium testing and twice weekly phosphorus determinations to check for hypocalcemia and hypophosphatemia. "Adverse renal effects . . . have been reported in about 12.5% of patients treated with Ganite," the labeling says. Ganite is contraindicated in patients "with severe renal impairment (serum creatinine >2.5 mg/dL)." The company is committed to performing four Phase IV studies: (1) "a pharmacokinetics study in hypercalcemic patients with varying degrees of renal dysfunction"; (2) "a pharmacokinetics study at different doses and schedules"; (3) a "comparative study with etidronate" [MGI Pharma's Didronel I.V.]; and (4) a "comparative study with pamidronate [Ciba-Geigy's Aredia]." Didronel I.V. U.S. sales were $ 3.2 mil. in 1990, up from $ 2.1 mil. in 1989, MGI Pharma reported Jan. 22. The company also announced that Knoll Canada will launch the product in Canada in March. Didronel was approved in Canada in December. Ciba-Geigy's Aredia was recommended for U.S. approval for hypercalcemia use on Oct. 22 by the Endocrinologic and Metabolic Drugs Advisory Committee. An NDA for Aredia was filed in December 1989 ("The Pink Sheet" Oct. 29, p. 11). The two pharmacokinetic studies will be used "to discuss whether any of the doses and schedules should be studied for safety and efficacy" in addition to the approved dose. "Also to be discussed at the completion of these studies will be safety and efficacy in patients who have relapses or who require a second course of treatment," FDA's approval letter specifies. The company says that the results of the comparative study to etidronate I.V. are ready for submission. FDA requested that data by March 1. FDA's approval letter also says that "we reserve comment as to the adequacy of the methods validation package for bulk gallium nitrate until the results of our laboratory tests on the samples submitted are available and have been evaluated." Johnson Matthey (West Chester, Pa.) will be the bulk supplier of the drug.