General Information

Osphena (ospemifene) is an estrogen agonist/antagonist with tissue selective effects. It binds to estrogen receptors, resulting in the activation of estrogenic pathways in some tissues and the blockade of estrogenic pathways in other tissues.

Osphena is specifically indicated for:

• the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.
• the treatment of moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy, due to menopause. 

Osphena is supplied as a tablet for oral administration. The recommended dose is one 60 mg tablet with food once daily. Use of Osphena should be for the shortest duration consistent with treatment goals and risks. For postmenopausal woman with a uterus, the addition of a progestin should be considered to reduce the risk of endometrial cancer. A woman without a uterus does not need a progestin.

Mechanism of Action

Osphena (ospemifene) is an estrogen agonist/antagonist with tissue selective effects. Its biological actions are mediated through binding to estrogen receptors. This binding results in activation of estrogenic pathways in some tissues (agonism) and blockade of estrogenic pathways in others (antagonism).

Side Effects

Adverse events associated with the use of Osphena may include, but are not limited to, the following:

• hot flush
• vaginal discharge
• muscle spasms
• headache
• hyperhidrosis
• vaginal hemorrhage
• night sweats

The Osphena drug label comes with the following Black Box Warning: Osphena is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, Osphena has estrogen agonistic effects. There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adequate diagnostic measures, including directed and random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. Estrogen-alone therapy has an increased risk of stroke and deep vein thrombosis (DVT). Osphena 60 mg had cerebral thromboembolic and hemorrhagic stroke incidence rates of 1.13 and 3.39 per thousand women years, respectively vs. 3.15 and 0 per thousand women years, respectively with placebo. For deep vein thrombosis, the incidence rate for Osphena 60 mg is 2.26 per thousand women years (2 reported cases) vs. 3.15 per thousand women years (1 reported case) with placebo.

Clinical Trial Results

The FDA approval of Osphena was based on three placebo-controlled clinical trials (two 12-week efficacy trials and one 52-week long-term safety trial).
Trial One
This 12-week, randomized, double-blind, placebo-controlled, parallel-group study enrolled 826 generally healthy postmenopausal women between 41 to 81 years of age with at least one moderate to severe vaginal symptom. Treatment groups included 30 mg or 60 mg Osphena or placebo. All women were assessed for improvement in the mean change from Baseline to Week 12 for the co-primary efficacy variables of: most bothersome symptom (MBS) of vulvar and vaginal atrophy (defined by each individual), percentage of vaginal superficial and vaginal parabasal cells on a vaginal smear, and vaginal pH.
Trial Two
This 12-week, randomized, double-blind, placebo-controlled, parallel-group study enrolled 919 generally healthy postmenopausal women between 41 to 79 years of age with moderate to severe vaginal dryness (dryness cohort) or moderate to severe dyspareunia (dyspareunia cohort). The subjects received 60 mg Osphena or placebo. Primary endpoints and study conduct were similar to those in Trial 1.
Trial Three
This 52-week, randomized, double-blind, placebo-controlled, long-term safety study enrolled 426 generally healthy postmenopausal women between 49 to 79 years of age with an intact uterus. Treatment groups included 60 mg Ospehna or placebo.
Study Results
In the 1st and 2nd clinical trial, the modified intent-to-treat population of women treated with Osphena when compared to placebo, demonstrated a statistically significant improvement (least square mean change from Baseline to Week 12) in the moderate to severe MBS of dyspareunia (1st trial p=0.0012, 2nd trial p<0.0001). A statistically significant increase in the proportion of superficial cells and a corresponding statistically significant decrease in the proportion of parabasal cells on a vaginal smear was also demonstrated (p<0.0001 for both). The mean reduction in vaginal pH between baseline and Week 12 was also statistically significant (p<0.0001). In the long-term safety study daily doses of 60mg of Ophena were well-tolerated with most treatment-emergent adverse events being mild or moderate in severity.