GLAXO's ETHAMOLIN AND OXISTAT ARE AMONG FDA's LATE DECEMBER APPROVALS; BRISTOL-MYERS IFOSFAMIDE, ASTA's MESNA & AMERSHAM's CERETEC ALSO CLEARED

Ethamolin (ethanolamine), an orphan product for prevention of rebleeding of esophageal varices, was one of at least two Glaxo drugs approved at year end. The injectable sclerosing agent cleared FDA Dec. 22 as a 1B drug, a new molecular entity representing a modest therapeutic gain. "Ethamolin is not indicated for the treatment of patients with esophageal varices that have not bled [and] there is no evidence that treatment of this population decreases the likelihood of bleeding," approved labeling states. "Sclerotherapy with Ethamolin has no beneficial effect upon portal hypertension, the cause of esophageal varices, so that recanalization and collateralization may occur, necessitating reinjection." Glaxo submitted its NDA in September 1984. The company began development of the drug in 1982 at the request of FDA, which had noted in the Federal Register that there were sufficient published and unpublished data to invite an NDA submission. Glaxo said that a first quarter 1989 launch of the product was likely. Ethamolin will be available in 2 ml ampules packaged in boxes of 10. Ethamolin was reviewed by FDA's Gastrointestinal Drugs Advisory Committee in late 1986. The panel agreed that ethanolamine was beneficial in treating initial bleeding and re-bleeding of esophageal varices, but was divided on an approval recommendation; four voted in favor of approval, two voted against and one abstained. One problem observed by the committee was the lack of data comparing the efficacy and toxicity of ethanolamine with the two more commonly used sclerosing agents, sodium tetradecyl sulfate and sodium morrhuate. One panel member voting for approval concluded that the drug was better than no treatment at all, and recommended that FDA re-examine the available data. A second Glaxo drug, the antifungal product Oxistat, (oxiconazole) was approved Dec. 30. The drug was given a 1C rating by FDA, representing a new molecular entity with little or no therapeutic gain. Oxiconazole was originally developed by the Swiss firm Siegfreid AG and licensed to Glaxo. Siegfried also licenses oxiconazole to VLI, now a part of American Home, which is developing a vaginal sponge product for treating yeast infections. Among the other late December approvals are Bristol-Myers' Ifex (ifosfamide) and Frankfurt-based Asta's Mesnex (mesna). The products, administered together for testicular cancer, have been available under a Treatment IND since December 1987 ("The Pink Sheet" Jan. 4, p. 10). FDA's Oncologic Drugs Advisory Committee recommended approval of ifosfamide at its April 19 meeting, stating as a condition that the drug be labeled only for use with the protective agent mesna. Ifex "is indicated for third line chemotherapy of germ cell testicular cancer," approved labeling states. "It should ordinarily be used in combination with a prophylactic agent for hemorrhagic cystitis, such as mesna." Labeling for mesna states that the injectable agent "has been shown to be effective as a prophylactic agent in reducing the incience of ifosfamide induced hemorrhagic cystitis." Mesna was classified by FDA as a 1B drug, and ifosfamide was classified as a 1C drug. The year-end approvals include two imaging agents: Amersham's Ceretec (technetium 99m HMPAO or exametazine) and Mallinckrodt's Optiray (ioversol). Ceretec, reviewed by FDA's Oncologic Drugs Advisory Committee in November, is indicated for "use as an adjunct in the detection of altered regional cerebral perfusion in strokes." Cerectec was approved as a 1B drug. Optiray, according to approved labeling, is indicated "for angiography throughout the cardiovascular system." Optiray is also indicated for "contrast enhanced computed tomographic imaging of the head and body, and intravenous excretory urography." The product received a 1C rating from FDA. A late December approval was also granted to Takeda's cephalosporin Ceradon (cefotiam). At the close of business hours Dec. 30, FDA had approved 20 new molecular entities throughout the year, 13 in December.