MERCK/ICI PHASING OUT PONALRESTAT STUDIES

MERCK/ICI PHASING OUT PONALRESTAT STUDIES, begun to develop the drug for nerve and eye damage associated with diabetes. Clinical trials of Merck's Prodiax and ICI's Statil for the treatment of long-term complications associated with diabetes (neuropathy, retinopathy and nephropathy) "have shown that the drug is well tolerated at the doses studied, but it has not proved to be effective," the companies said Jan. 17. No new studies will be started. However, some late stage testing will be completed, the firms said, "and results [will be] reviewed to confirm that all opportunities to show clinical efficacy have been exhausted." ICI had high hopes for ponalrestat, despite setbacks. The company had told securities analysts in March 1989 that it expected to file an NDA in 1990 for Statil, and that Phase III trials on 360 patients for diabetic neuropathy were to have been completed in mid-1989. ICI studies and Merck's own studies (on retinopathy) resumed in late 1988, after FDA lifted a limited clinical hold on ponalrestat and other aldose reductase inhibitors. The holds were placed on the drug class in late 1987 because the agents appeared to exacerbate neuropathy in studies in diabetic rats. Pfizer in 1985 halted testing of its drug, sorbinil, while the company tried to overcome, via different dosages, a 10% allergic reaction rate. A separate set of sorbinil studies at the National Eye Institute have been completed. Pfizer is now concentrating on early stage follow-up tests of compounds without the hypersensitivity potential of sorbinil. * The only other aldose reductase inhibitor actively being studied is AHP's tolrestat (Alredase). However, Wyeth-Ayerst has had its own setbacks. AHP's chance to be first to the market with an aldose reductase inhibitor was shattered in September 1986 when FDA's Endocrine & Metabolic Drugs Advisory Committee rejected tolrestat pending further study. Wyeth-Ayerst has not given up on the U.S. market. Tolrestat is currently in four Phase III studies in the U.S. for retinopathy: two for prevention and two for treatment, the company said. Tolrestat currently is marketed in Ireland for peripheral neuropathy and will be launched shortly in Mexico and Italy. By the end of the first quarter, the firm says it will have filings for approval on record in 27 countries, including 17 new ones this quarter.