FDA approves Imvexxy to treat moderate to severe dyspareunia due to menopause

The United States Food and Drug Administration (FDA) has approved TX-004HR: IMVEXXY (estradiol vaginal inserts) for the treatment of moderate-to-severe dyspareunia due to vulvar and vaginal atrophy (VVA) of menopause.

Imvexxy is the only product in its therapeutic class to offer a 4 mcg and 10 mcg dose, the 4 mcg representing the lowest approved dose of vaginal estradiol currently available in the market. The product will be available to the consumers in July.

Imvexxy should be administered intravaginally as follows: one vaginal insert daily for 2 weeks, followed by one insert twice weekly.

Brian Bernick, MD, Chief Clinical Officer of TherapeuticsMD, said in a press release, “Imvexxy is a bio-identical vaginal estrogen product that offers a fraction of the estrogen contained in the average doses of many existing products currently on the market.”

“Imvexxy is the only product specifically designed to be applicator-free. It dissolves completely without mess or additional cleanup and can be used any time of day. It allows women the freedom to immediately return to their normal daily activities. Studies showed that, in patients who used Imvexxy, systemic absorption of estradiol remained within postmenopausal range," he further added.

The product was approved following the results of Phase 3, randomized, double-blind, placebo-controlled study (REJOICE, NCT02253173), published in April 2017 issue of Journal Menopause. The study results showed that Imvexxy was safe and well tolerated in all three doses (4, 10, and 25 μg).

In 2 weeks there was considerable improvement in dyspareunia, even with the lowest dose of 4 μg and vaginal dryness as early as 6 weeks as compared to women who received placebo.

A substudy of the REJOICE trial evaluated the pharmacokinetics of the 4-μg and 10-μg inserts and placebo.

There was negligible or very low systemic absorption as evident by the serum levels with no accumulation of the drug as seen by the low endogenous values observed at day 84.

Other products like vaginal estradiol tablet, vaginal creams, and vaginal estrogen ring used for the treatment of VVA limit systemic estrogen absorption but does not completely eliminate it.

The Pharmacokinetics profile for Imvexxy (ie, negligible to very low systemic absorption) could allow clinicians to follow the recommendation of The North American Menopause Society (NAMS) to use low-dose vaginal estrogens without a concomitant progestin.

It could also be used for the treatment of vaginal symptoms in survivors of estrogen-dependent breast cancer as recommended by the American Congress of Obstetricians and Gynecologists (ACOG).

The most commonly reported side effect by the users of vaginal inserts was a headache but it was not statistically significant when compared to placebo users.

VVA affects an estimated 32 million postmenopausal women in the United States. Approximately 7% (2.3 million) of these women receive prescription treatment. In addition, nearly 1 out of 2 women will experience pain during intercourse due to VVA at some point during their lives.

Dr. Sheryl Kingsberg, President, North American Menopause Society, said in a statement issued by TherapeuticsMD, “Studies have shown that many women are not seeking treatment for VVA, and 81% are unaware that VVA is a treatable medical condition and part of a constellation of symptoms associated with loss of estrogens."

 "I am delighted that our patients will now have a convenient treatment option with IMVEXXY and hope that the excitement generated by this new option will encourage women to talk to their healthcare provider and get relief from their pain and discomfort due to VVA,” she further added.

The product comes with a boxed warning about the increased risk of endometrial cancer, stroke, deep vein thrombosis (DVT), and dementia when used as estrogen-alone therapy without progesterone therapy.

Imvexxy is contraindicated in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or history of breast cancer; known or suspected estrogen-dependent neoplasia; active DVT, PE, or history of these conditions; active arterial thromboembolic disease or a history of these conditions; known anaphylactic reaction or angioedema to Imvexxy; known liver impairment or disease; known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.

REJOICE Trial

TherapeuticsMD Press Release

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