Lasofoxifene

Generic Name: Lasofoxifene

Drug Type: Small Molecule

Chemical Formula: C_₂₈H_₃₁NO_₂

CAS Number: 180916-16-9

Unique Ingredient Identifier: 337G83N988

Overview

Lasofoxifene is a non-steroidal 3rd generation selective estrogen receptor modulator (SERM) that selectively binds to both ERα and ERβ with high affinity. It is a naphthalene derivative marketed for prevention and treatment of osteoporosis and for the treatment of vaginal atrophy. It was initially developed as Oporia by Pfizer as a treatment for postmenopausal osteoporosis and vaginal atrophy, in which were both rejected for approval by FDA. Later Fablyn was developed as a result of a research collaboration between Pfizer and Ligand Pharmaceuticals with a newly submitted New Drug Application in 2008. It gained approval by European Commission in March 2009. Ligand Pharmaceuticals signed a license agreement with Sermonix Pharmaceuticals for the development and commercialization of oral lasofoxifene in the USA.

Background

Indication

Investigated for use/treatment in postmenopausal osteoporosis to reduce the risk of both vertebral and novertebral fractures, as well as address other postmenopausal conditions, including reduction in risk of breast cancer and treatment of vulvar and vaginal atrophy (VVA)

Associated Conditions

No associated conditions information available.

Research Report

Published: May 13, 2025

Lasofoxifene Report

Name: Lasofoxifene Name (English): Lasofoxifene DrugBank ID: DB06202 Type: Small Molecule CAS Number: 180916-16-9

Lasofoxifene is a non-steroidal, third-generation selective estrogen receptor modulator (SERM). It selectively binds to both estrogen receptor alpha (ER$\alpha$) and beta (ER$\beta$) with high affinity, exhibiting both estrogenic and antiestrogenic activity depending on the tissue.

Pharmacology: Lasofoxifene acts as an estrogen agonist in bone, mimicking the effects of estrogen to reduce bone resorption and increase bone mineral density. It acts as an antagonist in the uterus and mammary glands by suppressing estrogen signaling.

Indications: It is marketed in some countries for the prevention and treatment of osteoporosis and for the treatment of vaginal atrophy in postmenopausal women. Lasofoxifene is also being investigated for the treatment of estrogen receptor-positive metastatic breast cancer, particularly in patients with ESR1 mutations, and for dyspareunia associated with vaginal atrophy.

Pharmacokinetics: Lasofoxifene demonstrates higher oral bioavailability compared to other SERMs. Peak plasma concentrations are reached in approximately 6-7 hours. It is primarily metabolized by hepatic CYP3A4/CYP3A5 and CYP2D6 enzymes, followed by glucuronidation and sulfation. The elimination half-life is approximately 6 days, with primarily fecal excretion of metabolites.

Clinical Trials: Lasofoxifene has been evaluated in phase II and phase III clinical trials for osteoporosis and breast cancer. Studies like ELAINE 1 and ELAINE 2 investigated its efficacy in advanced or metastatic ER+/HER2- breast cancer with ESR1 mutations. The phase III ELAINE 3 trial is ongoing, comparing lasofoxifene plus abemaciclib to fulvestrant plus abemaciclib in patients with ER+/HER2- metastatic breast cancer harboring an ESR1 mutation.

Continue reading the full research report