By Rebecca Bowers

EXECUTIVE SUMMARY

Annovera, a soft, reusable, flexible silicone ring containing segesterone acetate and ethinyl estradiol, has been approved by the U.S. Food and Drug Administration.

  • The ring measures 2 ¼ inches in diameter and is indicated for pregnancy prevention for up to one year. Women can insert and remove the ring by themselves. They leave the device in place for 21 days and then remove it for seven days during each cycle.
  • Each ring contains 103 mg of segesterone acetate and 17.4 mg ethinyl estradiol, which releases on average 0.15 mg/day of segesterone acetate and 0.013 mg/day of ethinyl estradiol.

Get ready to add a new vaginal contraceptive ring to the currently available birth control options in the United States. Annovera, a soft, reusable, flexible silicone ring containing segesterone acetate and ethinyl estradiol, has been approved by the U.S. Food and Drug Administration (FDA).

The ring measures 2 ¼ inches in diameter and is indicated for pregnancy prevention for up to one year. Women can insert and remove the ring by themselves. They leave the device in place for 21 days and then remove it for seven days during each cycle. Developed by the Population Council, Annovera has been licensed to TherapeuticsMD. The company anticipates that the ring will be available commercially in the third quarter of 2019, with launch later that year.

As part of its licensing agreement with the Population Council, TherapeuticsMD will provide significantly reduced pricing for the device to family planning clinics with federal Title X designation that serve lower-income women.

“This approval is a key first step toward introducing this product globally and better meeting the sexual and reproductive health needs of women, men and young people in the U.S. and around the world,” said Jim Sailer, executive director of the Center for Biomedical Research at the Population Council. “We are grateful to the dozens of researchers who have worked on this product, the donors who have funded its development, and most of all, to the thousands of women who volunteered to participate in clinical trials and made this all possible.”

Anita Nelson, MD, professor and chair of the obstetrics and gynecology department at Western University of Health Sciences, says she is “delighted” that a new option is available for women who want more choice, convenience, and control in family planning.

“The Population Council has been a leader in creatively and collectively addressing women’s contraceptive needs,” said Nelson, a principal investigator of the Phase 3 trials, in a statement. “It is exciting they are continuing to help empower women with another contraceptive choice.”

Research Backs Efficacy

Each ring contains 103 mg of segesterone acetate and 17.4 mg ethinyl estradiol, which releases on average 0.15 mg/day of segesterone acetate and 0.013 mg/day of ethinyl estradiol.

In awarding approval to the device, the FDA reviewed the results of 17 clinical trials, which included two Phase 3 trials for safety and efficacy. The advanced trials involved 2,308 women at 27 study sites in the United States, Latin America, Europe, and Australia. Study participants included healthy women ages 18 to 40 years who were instructed to use the device for 13 menstrual cycles, or one year. Based on the results of the research, approximately two to four women out of 100 may become pregnant during the first year of use.

The device carries a boxed warning regarding cigarette smoking and serious cardiovascular events. Women older than 35 years of age who smoke should not use Annovera, according to the package labeling.

The Annovera ring should not be used by women who have:

  • A high risk of arterial or venous thrombotic diseases;
  • Current or history of breast cancer or other estrogen- or progestin-sensitive cancer;
  • Liver tumors, acute hepatitis, or severe (decompensated) cirrhosis;
  • Undiagnosed abnormal uterine bleeding;
  • Hypersensitivity to any of the components of the device; or
  • Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.

The side effects of the new ring are similar to those of other combination hormonal birth control methods. These include headache/migraine, nausea/vomiting, yeast infections, abdominal pain, dysmenorrhea, breast tenderness, irregular bleeding, diarrhea, and genital itching.

Postmarketing studies will be conducted to evaluate the risks of venous thromboembolism associated with device use, as well as to examine the effects of CYP3A-modulating drugs and tampon use on the device’s pharmacokinetics.

Will New Method Be Accepted?

According to the approved package labeling, Annovera is to remain in the vagina continuously for 21 days, and then is removed for a one-week dose-free interval. Counsel women that withdrawal bleeding usually occurs during this time. Clinicians should instruct users to clean the ring with mild soap and warm water, pat it dry with a clean cloth towel or paper towel, and place it in its case during the dose-free interval. At the end of the dose-free interval, the ring should be cleaned prior to being placed back in the vagina for another 21 continuous-day cycle.

In acceptability research, 89% of women gave Annovera high marks for convenience, ease of use, and satisfaction with the device.1

Women may insert the ring either lying down, squatting, or standing. A woman inserts the ring by pressing the sides of the device together for insertion into the vagina. When the device is inserted properly, the vaginal system should be entirely in the vagina and behind the pelvic bone. Instruct women to note the day and time of insertion so that they may remove the ring three weeks later at approximately the same time and on the same day. A woman can remove the device by hooking an index finger into the ring inside the vagina, and gently pulling out the device.

The efficacy of the contraceptive ring depends on correct, consistent use. During a 28-day cycle, if a deviation causes the ring to be out of the vagina for less than seven days, pregnancy risk will not increase. However, if a deviation leads to the ring being out for more than seven days, pregnancy risk is increased and backup contraception is recommended.

How to Use the Device

A woman who wishes to use Annovera who has not used hormonal contraceptives or had a copper intrauterine device removed in the previous menstrual cycle may initiate device use during days two through five of her menstrual cycle. No backup contraception is needed. If a woman has irregular menstrual cycles or if the start is more than five days from the last menstrual bleeding, an additional barrier method of birth control, such as a male condom or spermicide, should be used during coitus for the first seven days.

How about women switching from combined hormonal contraception? Use of Annovera may be initiated on any day of the method’s cycle (day 1-28) without the need for backup contraception. However, no more than seven hormone-free days should occur before starting Annovera.

Women who previously have used progestin-only methods, such as the contraceptive shot, implant, pill, or intrauterine device, may use Annovera if they have no contraindications to ethinyl estradiol. For patients switching from progestin-only pills, Annovera should be initiated at the time of the next pill. For those switching from an injection, the ring should be initiated at the time of the next scheduled injection. If moving from an implant or a progestin-only intrauterine device, Annovera should be started at the time of implant or device removal. In all such cases, an additional barrier method, such as a male condom or spermicide, should be used during coitus for the first seven days of ring use.

In new mothers, Annovera should not be started earlier than four weeks after childbirth, and only in those women who choose not to breastfeed. When device use is initiated four weeks or more postpartum, women should use an additional contraception method, such as male condoms or spermicide, during coitus for the first seven days if no period has yet been recorded. For new mothers who choose to breastfeed, Annovera should not be used until weaning.

REFERENCE

  1. Merkatz RB, Plagianos M, Hoskin E, et al. Acceptability of the Nestorone®/ethinyl estradiol contraceptive vaginal ring: Development of a model; implications for introduction. Contraception 2014;90:514-521.