Options being eyed for transdermal contraception
Executive Summary
Transdermal contraception provides a family planning option that is not dependent on daily dosing. The only transdermal contraceptive approved in the United States is the Ortho Evra patch.
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An investigational combination hormonal contraceptive patch has been designed to deliver a low dose of ethinyl estradiol and levonorgestrel comparable to low-dose combination oral contraceptives. Developed by Agile Therapeutics as AG200-15, the drug is under U.S. regulatory review.
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Bayer HealthCare has submitted an application for marketing authorization in the European Union for a transparent low-dose contraceptive patch containing ethinyl estradiol/gestodene. Gestodene, while used in as a contraceptive agent in Europe for many years, is not available in any U.S.-approved contraceptive.
Transdermal contraception provides a family planning option that is not dependent on daily dosing. While potential options are in development, the only transdermal contraceptive approved in the United States is the Ortho Evra patch, marketed by Ortho Women's Health & Urology, Raritan, NJ.
Evra received Food and Drug Administration (FDA) approval in 2001. Since that time, its labeling has been edited to address issues relating to the risk of venous thromboembolism and exposure to contraceptive hormones seen with Ortho Evra as compared to certain combined oral contraceptives. (See the Contraceptive Technology Update article, "Set to change: Patch, drospirenone OC labels," February 2012, p. 13.)
Many women prefer using a weekly patch to having to remember daily oral contraceptive tablets, says Andrew Kaunitz, MD, professor and associate chair in the Obstetrics and Gynecology Department at the University of Florida College of Medicine — Jacksonville. The currently marketed ethinyl estradiol/ norelgestromin patch results in blood levels similar to those associated with use of high-dose 50 mcg ethinyl estradiol oral contraceptives, says Kaunitz.
An investigational combination hormonal contraceptive patch has been designed to deliver a low dose of ethinyl estradiol and levonorgestrel comparable to low-dose combination oral contraceptives. Developed by Agile Therapeutics of Princeton, NJ, as AG200-15, the drug is under review by the FDA. The company has registered the trademarked name Twirla for the investigational drug. It is designed to deliver 120 mg/day levonorgestrel with 25 mg/day ethinyl estradiol. (To read more about the drug, see the CTU articles "Check methods with combined hormones," April 2013, p. 40, and "Data out on potential contraceptive patch," August 2012, p. 88.)
In a phase III pivotal trial of AG200-15, results suggest the study drug had significantly greater compliance (defined as no missed days of contraception in the cycle) than an oral contraceptive.1
Of 1,328 women (mean age, 26.4 years; 60% new hormonal contraceptives users; 46% non-Caucasian; 33% obese), 998 received the patch and 330 received an oral contraceptive for the first six study cycles. Women in the study were treated for one year (13 cycles) with the patch or for six cycles with the Pill, followed by seven cycles of patch use. Subjects recorded patch application and pill-taking on diary cards. Cycles with perfect compliance were defined as cycles with 21 days of patch wear without missed days or any patch worn for more than seven days or cycles with 21 days of pill-taking without days of missed pills.
Over the first six cycles, the percentage of cycles with perfect compliance was significantly higher in the patch versus the pill group (90.5% vs. 78.8%, P less than .001). Compliance with the patch improved over the six treatment cycles, while compliance with the Pill worsened over the six cycles.1
Additional research indicates the investigational low-estrogen patch is as effective as conventional oral contraceptives; an additional finding of the trial is that the efficacy of the investigational patch did not decline in obese women.2
"Should this lower-estrogen patch receive FDA-approval, our patients would have access to a lower dose transdermal contraceptive system," says Kaunitz, who served as lead clinical investigator in the AG200-15 trials.
Potential option eyed
Berlin, Germany-based Bayer HealthCare submitted an application for marketing authorization in the European Union for a new transparent low dose contraceptive patch containing ethinyl estradiol/ gestodene in September 2012, confirms company spokesperson Marcy Funk. Named FC-Patch Low, the patch is transparent and contains 0.55 mg ethinyl estradiol and 2.1 mg gestodene. While gestodene has been in use as a contraceptive agent in European countries for more than 20 years, no U.S.-approved birth control method contains it.
In a 2013 study, a combined oral contraceptive containing 0.03 mg of ethinyl estradiol and 0.15 mg levonorgestrel and the Bayer patch showed comparable influence on hemostatic endpoints.3 Both treatments were well-tolerated by subjects.3
Earlier research indicates that the good skin absorption properties of gestodene, and the low absolute dose required for contraceptive efficacy, suggest it can be offered in a small patch size.4,5
REFERENCES
- Kaunitz A, Archer DF, Foegh M. Increased compliance with a low-dose combination contraceptive patch (AG200-15) compared with a low-dose combination oral contraceptive (COC) in a phase 3 clinical trial. Contraception 2012; 86(2):178.
- Kaunitz AM, Mishell DR, Foegh ML. Comparative Phase 3 Study of AG200-15, a Low-Dose Estrogen, and Levonorgestrel Contraceptive Patch. Presented at the 60th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists. San Diego; May 2012.
- Junge W, Heger-Mahn D, Trummer D, et al. Investigation of the hemostatic effect of a transdermal patch containing 0.55 mg ethinyl estradiol and 2.1 mg gestodene compared with a monophasic oral contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel: an open-label, randomized, crossover study. Drugs R D 2013; 13(3):223-233.
- Heger-Mahn D, Warlimont C, Faustmann T, et al. Combined ethinyl estradiol/gestodene contraceptive patch: two-center, open-label study of ovulation inhibition, acceptability and safety over two cycles in female volunteers. Eur J Contracept Reprod Health Care 2004; 9(3):173-181.
- Benagiano G, Primiero FM, Farris M. Clinical profile of contraceptive progestins. Eur J Contracept Reprod Health Care 2004; 9(3):182-193.
