Malone_1998_IDrugs_1_232

Orlistat (Xenical) is a lipase inhibitor developed by Roche for the treatment of obesity, which has been approved in New Zealand [288631], and several countries in Latin America and the Far East. Roche expects to introduce Xenical in its first markets later this year [287131] Analysts predict that it will be a $$1 billion drug for Roche [247775]. In May 1998, the US FDA issued a letter of approval for orlistat but final approval is still subject to certain conditions, including submission of follow-up safety data from the ongoing clinical trials and agreement on final labeling. Roche expects that this will be achieved by the first quarter of 1999 [287131]. In March 1998, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee tied, 5 to 5, on recommending approval of orlistat [281197]. The EC's Committee on Proprietary Medicinal Products has given positive opinions to orlistat submitted under the centralized approvals procedure [283245]. It was also noticed that further clinical trials would be needed to rule out any links between breast cancer and the drug. In phase III studies, nine female patients taking orlistat developed breast neoplasms compared to one patient in the placebo group. After the 18-month follow-up, Roche found that two more women treated with 120 mg tid, and one more on placebo, developed breast cancer. Roche has estimated the relative risk of acquiring breast cancer through orlistat therapy to be 5.9-fold greater than through placebo, or 3.6-fold greater, including post-treatment follow-up; this risk has been shown to be statistically significant [282157]. In August 1997, Roche withdrew its NDA in order to gain more time to submit further analyses of available data to secure approval. The FDA reported that the data submitted supports orlistat's efficacy, but asked Roche to gather further information on breast cancer cases observed in clinical trials [260694]. The NDA for orlistat was resubmitted by Roche in November 1997 [269450].