Arzoxifene is a selective estrogen receptor modulator. It is a potent estrogenantagonist in mammary and uterine tissue while acting as an estrogen agonist to maintain bone density and lower serum cholesterol. Arzoxifene is a highly effective agent for prevention of mammary cancer induced in the rat by the carcinogen nitrosomethylurea and is significantly more potent than raloxifene in this regard. Arzoxifene is devoid of the uterotrophic effects of tamoxifen, suggesting that, in contrast to tamoxifen, it is unlikely that the clinical use of arzoxifene will increase the risk of developing endometrial carcinoma.
In a phase 3 clinical study in postmenopausal women, arzoxifene was shown to increase bone spine and hip mineral density and had no effect on the uterus and endometrium.
Lilly announced in August 2009 that preliminary results from a five year clinical study showed that arzoxifene met its primary endpoints of reduction in vertebral fractures and breast cancer in postmenopausal women. However arzoxifene failed to meet secondary endpoints of reduction in non-vertebral fractures and cardiovascular events and improvements in cognitive function. Based on these results, Lilly announced they are discontinuing further development of the drug and would not seek regulatory approval.
^Overk CR, Peng KW, Asghodom RT; et al. (2007). "Structure-activity relationships for a family of benzothiophene selective estrogen receptor modulators including raloxifene and arzoxifene". ChemMedChem2 (10): 1520–6. doi:10.1002/cmdc.200700104. PMID17654759.
^Bolognese M, Krege JH, Utian WH, Feldman R, Broy S, Meats DL, Alam J, Lakshmanan M, Omizo M (July 2009). "Effects of arzoxifene on bone mineral density and endometrium in postmenopausal women with normal or low bone mass". J. Clin. Endocrinol. Metab.94 (7): 2284–9. doi:10.1210/jc.2008-2143. PMID19351734.