Arena preclinical data

Arena and partner Eisai Co. Ltd. (Tokyo:4523; Osaka:4523, Tokyo, Japan) reported data from a re-adjudication of female rat mammary tumor diagnoses for lorcaserin in a 2-year carcinogenicity study showing that the percentage of malignant tumors was lower for all dose groups of the obesity candidate than in the initial report included in Arena's 2009 NDA. The companies hope the data will address FDA's concerns about an increased rate of mammary tumors in female rats exposed to the serotonin (5-HT2C) receptor agonist. FDA raised the issue in a complete response letter last October and asked for a blinded re-adjudication of all mammary and lung tissues by a panel of 5 pathologists to better classify between benign and malignant tumors (see BioCentury, Nov. 1, 2010). The initial review of the tissues was conducted by only 1 pathologist. Arena plans to respond by year end.

According to the blinded re-adjudication, 32.3%, 36.9% and 68% of rats receiving 10, 30 and 100 mg/kg/day lorcaserin, respectively, had malignant tumors vs. 40% for undisclosed control-treated rats. In the initial report, 52.3%, 53.9% and 80% of rats receiving low-, mid- and high-dose lorcaserin, respectively, had malignant tumors vs. 43.1% for controls. Additionally, the incidence of benign mammary tumors was higher for all dose groups of lorcaserin compared to Arena's initial report. Specifically, the re-adjudication showed that 83.1%, 84.6% and 68% of rats receiving 10, 30 and 100 mg/kg/day lorcaserin, respectively, had benign tumors vs. 36.9% for controls. In the initial report, 72.3%, 81.5% and 60% of rats receiving low-, mid- and high-dose lorcaserin, respectively, had benign tumors vs. 30.8% for controls. The re-adjudication was conducted by a group of 5 pathologists contracted by Arena in consultation with FDA. The agency has not conducted its own review of the data, according to the company. ...