A technology evaluation of Annovera: a segesterone acetate and ethinyl estradiol vaginal ring used to prevent pregnancy for up to one year

ABSTRACT

Introduction

The segesterone acetate and ethinyl estradiol contraceptive vaginal ring (SA/EE CVR) was FDA-approved in August 2018 and is now available in the U.S. The CVR is placed vaginally for 21 days followed by a 7-day ring-free interval, when withdrawal bleeding typically occurs. One ring can be used for up to a year (13 cycles).

Areas covered

This review summarizes this novel method of contraception, including the delivery system and the hormonal components. We describe the potential market, how it is used, the pharmacokinetic properties of the device, and results of clinical trials including efficacy, bleeding profile, acceptability, and safety.

Expert opinion

The SA/EE CVR represents the first long-lasting user-controlled hormonal contraceptive device. The bleeding pattern is highly favorable and consistent over the entire year and is associated with very low discontinuation. Efficacy and safety are similar to other methods of combined hormonal contraceptives. Unscheduled ring removals increase the risk of failure. Further studies are needed to evaluate continuous use of the ring for greater than 21 days, and potential non-contraceptive benefits of the ring such as reduced menstrual bleeding.

KEYWORDS:

• Annovera
• combined hormonal contraception
• vaginal ring contraception

Article highlights

• The segesterone acetate and ethinyl estradiol contraceptive vaginal ring (SA/EE CVR) is the first user-controlled long-lasting method of hormonal contraception. It is used in a 21-day in and 7-day out regimen, and each ring lasts for up to one year (13 cycles).

• SA is a 19-norprogesterone derivative designed to specifically target the progesterone receptor with substantially reduced or no binding to the androgen receptor, estrogen receptor, and mineralocorticoid receptor.

• Two Phase III studies included 2,265 participants and forty pregnancies occurred among women under 35 years, leading to a calculated Pearl Index of 2.98 per 100 woman-years. The Pearl index was 2.10 among women who did not report any unscheduled ring removals greater than 2 hours.

• The bleeding pattern was highly consistent over the course of the year-long Phase III studies, and only 1.8% of participants discontinued the CVR due to unacceptable bleeding.

• In clinical studies, the incidence of adverse events and changes in lipids, metabolic markers, and other laboratory values were as expected for a combined estrogen/progestin hormonal contraceptive method. Ring expulsions were common, occurring in half of clinical trial participants, but this led to discontinuation in only 1.5%.

Declaration of interest

EA Micks has received research funding from Sebela and is a Nexplanon trainer for Merck. JT Jensen has received payments for consulting from Abbvie, Cooper Surgical, Bayer Healthcare, Merck, Sebela, TherapeuticsMD and the Population Council. OHSU has received research support from Abbvie, Bayer Healthcare, Daré, Estetra SPRL, Medicines360, Merck, and Sebela. These companies and organizations may have a commercial or financial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a consultant in clinical development and provide services to other companies producing contraceptive products. As a former co-worker of the company Organon, they have contributed to the clinical development of NuvaRing. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.