Executive Summary

CIBA-GEIGY ACE INHIBITOR LOTENSIN SCHEDULED FOR JULY 23 LAUNCH, the firm announced, following the June 25 approval of the drug for hypertension. The agency gave Lotensin (benazepril) a "1C" therapeutic rating (new chemical entity representing little or no medical gain over existing therapies). The product is indicated for treatment of hypertension, either "alone or in combination with thiazide diuretics," approved labeling states. It will be available in tablets in concentrations of 5, 10, 20 and 40 mg. Lotensin has been approved in 13 other countries but to date is marketed only in France and Denmark. The company is emphasizing the product's potential for use in the elderly population. A Ciba-Geigy press statement notes that the physician insert for the product is "one of the first to reflect some of the FDA's new geriatric labeling requirements." Under the heading "Geriatric Use," the labeling states: "Of the total number of patients who received benazepril in U.S. clinical studies of Lotensin, 18% were 65 or older while 2% were 75 or older. No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out." Benazepril is the second angiotensin enzyme-converting inhibitor with labeling that carries information specifically on geriatric use. The package insert for fosinopril (Bristol-Myers Squibb's Monopril) also states that "no overall difference in safety or effectiveness" was found in the elderly, which constituted 13% of fosinopril subjects, versus younger patient populations. Fosinopril was approved in May; it will be copromoted by Boehringer-Ingelheim ("The Pink Sheet" May 20, T&G-1). There is no geriatric use section in labeling for captopril (Bristol-Myers Squibb's Capoten), lisinopril (Merck's Prinivil and Stuart's Zestril) or enalapril (Merck's Vasotec). There will soon be seven ACE brands on the U.S. market; three of the brands are new in 1991: Lotensin, Monopril and Hoechst's Altace (ramipril). FDA has set an impressive pace of new molecular entity approvals through the first half of this year. Only seven NMEs had gained approval by this time last year, compared to the 11 approved thus far in 1991. The agency's approval record has largely been overshadowed by the spotlight on enforcement actions. FDA is requiring further carcinogenicity study of Lotensin. In the June 25 approval letter to the firm, the agency's Office of Drug Evaluation I Director Robert Temple, MD, noted that Ciba- Geigy has "committed to repeat [a] 90-day dose range-finding study in rats." Temple added that the firm "further agreed" to repeat a two-year carcinogenicity study "using the [maximum tolerated dose(BRACKET)" if a two-year carcinogenicity study previously performed does not approach the maximum tolerated dose.