Arena Pharmaceuticals, Inc. and Eisai Inc. announced results from a Pathology Working Group's (PWG) re-adjudication of female rat mammary tumour diagnoses from a two-year rat carcinogenicity study of lorcaserin. Arena convened the PWG in response to the lorcaserin Complete Response Letter (CRL), which questioned the certainty of the female rat mammary tumour classifications. The PWG reviewed relevant tissues and reported that mammary fibroadenomas (benign tumours) were distinguishable from mammary adenocarcinomas (malignant tumours).

The PWG reported shifts in the numbers of both tumour types from the initial report included in the lorcaserin New Drug Application (NDA) and that adenocarcinomas were no longer numerically higher than the control group in the lorcaserin low- and mid-dose groups.

“We believe the PWG's report should further clarify the female rat mammary tumour diagnoses which, in combination with other data, may be helpful in assessing human risk,” said William R Shanahan, MD, Arena's senior vice president and chief medical officer.

The PWG's re-adjudication is one of the activities intended to address the observation of mammary tumours in female rats and is part of the overall plan to submit a response to the lorcaserin CRL. Additional activities intended to address the CRL are ongoing.

The PWG consisted of five pathologists contracted by Arena. Arena consulted the US Food and Drug Administration (US FDA) in selecting these pathologists. According to the PWG's re-adjudication, the incidence of adenocarcinomas was numerically lower than the control group in both the lorcaserin low (10 mg/kg/day) and mid (30 mg/kg/day) dose groups and was statistically higher than the control group in the lorcaserin high (100/kg/day) dose group, and the incidence of fibroadenomas was statistically higher than the control group for all three lorcaserin dose groups. The incidences of adenocarcinomas and fibroadenomas from the initial report and the PWG report are summarized below.

In addition, the PWG reported that the incidence of mammary adenomas (benign tumours) was 1.5%, 3.1%, 7.7%, 5.3%, the incidence of mammary carcinosarcomas (malignant tumours) was 0%, 0%, 0%, 1.3%, the incidence of lung metastases of mammary gland origin was 0%, 1.5%, 7.7%, 6.7%, and the incidence of lung metastases of non-mammary gland origin was 0%, 4.6%, 6.2%, 2.7% for the control and lorcaserin low-, mid- and high-dose groups, respectively. No mammary adenomas were diagnosed in the initial report, the incidence of mammary carcinosarcomas did not change from the initial report, and the incidence of lung metastases of both mammary and non-mammary origin were reported together in the initial report as 0%, 6.2%, 13.8% and 8.0% for the control and lorcaserin low-, mid- and high-dose groups, respectively.

It is important to note that the US FDA may have a different interpretation of the re-adjudication and subsequent conclusions of the PWG. There may be other factors in addition to incidence that may contribute to the FDA's assessment of human risk for the finding of mammary tumours in female rats. The information reported in this press release summarizes a report containing voluminous and detailed data that will be reviewed by the FDA. The FDA may analyse or weigh the importance of data from the report differently than the PWG or Arena.

Lorcaserin is an investigational drug candidate intended for weight management, including weight loss and maintenance of weight loss, in patients who are obese (BMI > 30) or patients who are overweight (BMI >27) and have at least one weight-related co-morbid condition. Lorcaserin is a new chemical entity that is believed to act as a selective serotonin 2C receptor agonist. The serotonin 2C receptor is expressed in the brain, including the hypothalamus, an area believed to be involved in the control of appetite and metabolism. Arena has patents that cover lorcaserin in the United States and other jurisdictions that in most cases are capable of continuing into 2023 without taking into account any patent term extensions or other exclusivity Arena might obtain.

Arena submitted a NDA for lorcaserin to the FDA in December 2009, and the FDA issued a CRL in October 2010. Arena's wholly owned subsidiary, Arena Pharmaceuticals GmbH, has granted Eisai Inc. exclusive rights to market and distribute lorcaserin in the United States subject to FDA approval of the NDA for lorcaserin.

Arena is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral drugs that target G protein-coupled receptors, an important class of validated drug targets, in four major therapeutic areas: cardiovascular, central nervous system, inflammatory and metabolic diseases.