In postmenopausal women with osteoporosis, lasofoxifene at a dose of 0.5 mg per day was associated with reduced risks of nonvertebral and vertebral fractures, ER-positive breast cancer, coronary heart disease, and stroke but an increased risk of venous thromboembolic events.[3][4]
In studies of breast cancer prevention, lasofoxifene showed a 79% reduction in breast cancer incidence and an 83% reduction specific incidence ofestrogen receptor-positive breast cancers, which is significantly higher than reductions found with the related SERMstamoxifen andraloxifene.[5] In accordance, anetwork meta-analysis of SERMs for breast cancer prevention found the highest reduction in risk with lasofoxifene of all the drugs.[6] The reduction was even greater than that observed witharomatase inhibitors, which have generally been found to confer a greater risk reduction than SERMs.[6] It also has shown promise inESR1 mutant patients with 'approximately 40% of patients harboring this mutation'.[7]
Lasofoxifene selectively binds to bothERα andERβ with highaffinity.[8] ItsIC50 for ERα (1.5 nM) is similar to that ofestradiol (4.8 nM) and is at least 10-fold higher than those of tamoxifen.[3]
Effect:+ =Estrogenic /agonistic.± = Mixed or neutral.– =Antiestrogenic /antagonistic.Note: SERMs generally increase gonadotropin levels in hypogonadal and eugonadal men as well as premenopausal women (antiestrogenic) but decrease gonadotropin levels in postmenopausal women (estrogenic).Sources: See template.
In January 2008, Ligand Pharmaceuticals, through its marketing partner,Pfizer, submitted aNew Drug Application for lasofoxifene, which is expected to be marketed under the tradename Fablyn. Lasofoxifene was approved in the EU under the brand name Fablyn by the EMEA in March 2009.[11]
^Gennari L, Merlotti D, Martini G, Nuti R (September 2006). "Lasofoxifene: a third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis".Expert Opinion on Investigational Drugs.15 (9):1091–103.doi:10.1517/13543784.15.9.1091.PMID16916275.S2CID20693299.
^abGennari L (June 2006). "Lasofoxifene: a new type of selective estrogen receptor modulator for the treatment of osteoporosis".Drugs of Today.42 (6):355–67.doi:10.1358/dot.2006.42.6.973583.PMID16845439.
^Gennari L (September 2009). "Lasofoxifene, a new selective estrogen receptor modulator for the treatment of osteoporosis and vaginal atrophy".Expert Opinion on Pharmacotherapy.10 (13):2209–20.doi:10.1517/14656560903127241.PMID19640205.S2CID21020484.
^Lednicer D, Emmert DE, Lyster SC, Duncan GW (September 1969). "Mammalian antifertility agents. VI. A novel sequence for the preparation of 1,2-disubstituted 3,4-dihydronaphthalenes".Journal of Medicinal Chemistry.12 (5):881–5.doi:10.1021/jm00305a038.PMID5812203.
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