FDA Advisory Committee: benefits of lasofoxifene outweigh risks

The committee voted on issues related to benefits, risks and safety and the quality of available data.

The FDA Advisory Committee for Reproductive Health Drugs voted nine to three that the benefits of lasofoxifene are likely to outweigh the risks when used in a subgroup of postmenopausal women with osteoporosis.

The committee assembled on Monday to review data available for the osteoporosis drug, lasofoxifene (Fablyn, Pfizer).

“The data demonstrated that the medication met its primary objective: to lower the risk for new or worsening vertebral fractures,” Julia V. Johnson, MD, professor and vice chair of gynecology at the University of Vermont College of Medicine and panel member, told Endocrine Today.

However, most panel members agreed that there was not enough data available to determine whether all-cause mortality reflected a true increase in the number of lasofoxifene-related deaths.

Available data

According to a briefing document, the advisory committee considered results from the PEARL study, a prospective, randomized, double-blind, placebo-controlled phase-3 trial, to determine lasofoxifene’s efficacy. Two doses of lasofoxifene were administered in the trial: 0.25 mg and 0.5 mg.

At three years, researchers found that lasofoxifene 0.5 mg reduced radiographic vertebral and nonvertebral fractures in postmenopausal women, including those with severe osteoporosis. Researchers also reported a reduced frequency of multiple new or worsening radiographic vertebral fractures for both dose groups, compared with placebo. Two safety issues found in the study were an increase in venous thromboembolic events and an increased incidence of diagnostic uterine procedures.

Benefits and risks

Compared with approved hormonal products currently available for the treatment of postmenopausal osteoporosis and menopausal symptoms, most committee members voted that the increased risk for venous thromboembolism related to treatment with lasofoxifene was not of great concern.

However, the adverse effects associated with lasofoxifene, like endometrial thickening and vaginal bleeding, did concern some experts.

“I really do think that it is going to put women at an increased risk for gynecologic procedures. If this does go forward, significant education, regarding the interpretation of ultrasound and endometrial biopsies, for gynecologists, primary care providers and pathologists will be critical, otherwise we’ll see a marked increase in procedures done to women,” Johnson said during the discussion.

Nine out of thirteen members voted that the benefits of treatment with lasofoxifene outweigh the risks in postmenopausal women with osteoporosis at high risk for fractures and those who are unable to use bisphosphonates. Almost all committee members agreed that head-to-head drug trials are needed to make concrete decisions.

“I’m really dismayed that we don’t have a head-to-head trial. Without head-to-head trials, we really can’t make absolute definitions about which drugs work and which do not. Trying to hold this drug to the same standard as the first drug that was approved in this category requires head-to-head trial data,” said committee member Clifford Rosen, MD, director of the Maine Center for Osteoporosis Research and Education Laboratory, St. Joseph Hospital and professor at The Jackson Laboratory. – by Stacey L. Adams