Effects of ospemifene on genitourinary health assessed by prospective vulvar-vestibular photography and vaginal/vulvar health indices

Abstract

This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.

Ospemifene for the treatment of menopausal vaginal dryness, a symptom of the genitourinary syndrome of menopause

“…A recent 12-week, randomized, double-blind, placebocontrolled phase 3 study (NCT02638337 [41]) reported the use of vulvar-vestibular photography and direct visual assessments as secondary outcomes in 631 postmenopausal women with moderate to severe vaginal dryness [55]. Women aged 40-80 years with vaginal dryness as their MBS, ≤5% superficial cells in VMI, and vaginal pH >5.0 took ospemifene or placebo [55].…”

“…A recent 12-week, randomized, double-blind, placebocontrolled phase 3 study (NCT02638337 [41]) reported the use of vulvar-vestibular photography and direct visual assessments as secondary outcomes in 631 postmenopausal women with moderate to severe vaginal dryness [55]. Women aged 40-80 years with vaginal dryness as their MBS, ≤5% superficial cells in VMI, and vaginal pH >5.0 took ospemifene or placebo [55]. Tissue changes from baseline to 12 weeks were assessed with the Vulvar Imaging Assessment Scale (VIAS; unvalidated 4-point scale) including 9 criteria (labia majora, labia minora, clitoris size, introital tissue elasticity, introital color, introital erythema, introital moisture, urethral glans prominence, and other findings; maximum score 27) [55].…”

“…Women aged 40-80 years with vaginal dryness as their MBS, ≤5% superficial cells in VMI, and vaginal pH >5.0 took ospemifene or placebo [55]. Tissue changes from baseline to 12 weeks were assessed with the Vulvar Imaging Assessment Scale (VIAS; unvalidated 4-point scale) including 9 criteria (labia majora, labia minora, clitoris size, introital tissue elasticity, introital color, introital erythema, introital moisture, urethral glans prominence, and other findings; maximum score 27) [55]. The Vaginal Health Index (VHI; unvalidated scale) assessed overall elasticity, fluid secretion, pH, condition of the epithelial mucosa, and moisture (each on a 5-point scale; maximum score 25), and the Vulvar Health Index (VuHI; unvalidated scale) assessed labia majora, labia minora, clitoris, introital tissue elasticity, color, discomfort and pain, and any other findings (each on a 4-point scale; maximum score 21) [55].…”

“…VIAS results showed significant improvements (decreases) from baseline to week 12 in vulvar-vestibular tissue appearance with ospemifene versus placebo (difference in least-square mean [LSM] change for total score, -1.0; p = 0.015) [55]. Both VHI and VuHI total scores also significantly improved (indicated by an increase and decrease, respectively) at week 12 (differences in LSM change: VHI, 2.8; VuHI, -1.2; both comparisons, p < 0.0001 vs placebo), and these changes were already apparent at week 4 [55].…”

“…VIAS results showed significant improvements (decreases) from baseline to week 12 in vulvar-vestibular tissue appearance with ospemifene versus placebo (difference in least-square mean [LSM] change for total score, -1.0; p = 0.015) [55]. Both VHI and VuHI total scores also significantly improved (indicated by an increase and decrease, respectively) at week 12 (differences in LSM change: VHI, 2.8; VuHI, -1.2; both comparisons, p < 0.0001 vs placebo), and these changes were already apparent at week 4 [55]. Representative vulvar-vestibular photographs from before and prospectively after ospemifene treatment showed increased tissue in the labia minora, decreased erythema of the distal urethral meatus, lesser prominence of the distal urethra, decreased vestibular petechiae and pallor, and improvement of introital stenosis, compared with no improvements in the placebo group (Figure 2) [55].…”