Investigational Contraceptive Patch Clears FDA Panel Vote
EXECUTIVE SUMMARY
Twirla, an investigational combined hormonal contraceptive patch, is under review by the FDA. In an October 2019 meeting, the patch received a 14 to 1 vote from the FDA’s Bone, Reproductive, and Urologic Drugs Advisory Committee.
• A combined hormonal contraceptive patch containing ethinyl estradiol and levonorgestrel, Twirla is designed to be applied once weekly for three weeks, followed by a week without a patch.
• Although the investigational patch is as effective as conventional oral contraceptives, the amount of estrogen released from the patch is substantially lower than that associated with the currently marketed patch. The risk of venous thromboembolism with Twirla may be lower than with the currently available patch.
When it comes to combined hormonal contraception, there are only three nondaily options available: two contraceptive vaginal rings (Annovera, containing segesterone acetate and ethinyl estradiol, and NuvaRing, containing etonogestrel and ethinyl estradiol), and the Xulane contraceptive transdermal system, formulated with norelgestromin and ethinyl estradiol.
A second transdermal system, the investigational combined hormonal contraceptive patch Twirla, is under review by the FDA. In an October 2019 meeting, the patch, manufactured by Agile Therapeutics, received a 14 to 1 (with one abstention) vote from the FDA’s Bone, Reproductive, and Urologic Drugs Advisory Committee. A combined hormonal contraceptive patch containing ethinyl estradiol and levonorgestrel, Twirla is designed to be applied once weekly for three weeks, followed by a week without a patch. Research suggests the efficacy and safety of the Twirla patch are comparable to those of a combined pill.1
Women are interested in nondaily options. The results of an international survey indicate that nearly half of respondents said they would prefer such an option. About half of respondents said they would like to conceive in the near future, suggesting that they are unlikely to favor long-acting options.2
Although the investigational patch is as effective as conventional oral contraceptives, the amount of estrogen released from the patch is substantially lower than that associated with the currently marketed patch; accordingly, the risk of venous thromboembolism with Twirla may be lower than with Xulane, says Andrew Kaunitz, MD, associate chair of the department of obstetrics and gynecology at the University of Florida College of Medicine-Jacksonville and medical director of the UF Health Women’s Specialists — Emerson.
“Accordingly, if it receives FDA approval, the lower dose Twirla patch will be a welcome addition for U.S. clinicians who prescribe contraceptives, and our patients,” says Kaunitz.
Check Weight Data
Results from the Twirla clinical trial indicate the overall Pearl Index in the primary efficacy population (women ages 35 or below, regardless of body mass index [BMI] or weight) was 5.83 (95% confidence interval [CI]: 4.45-7.21). In women with BMI below 30 kg/m2, the Pearl Index was 4.34 (95% CI: 2.86-5.82), while in women with BMI equal or above 30 kg/m2, the Pearl Index was 8.64 (95% CI: 5.79-11.50).3
Many women in the United States are classified as overweight. In an analysis of 5,900 women participating in the National Survey of Family Growth, 24.5% of women ages 20-44 years were overweight (BMI 25.0-29.9 kg/m2) and 23% were obese (BMI 30.0 kg/m2 or higher).4 Agile Therapeutics has proposed that a Limitation of Use statement be included in the product labeling regarding lower efficacy in women with a BMI equal or above 30 kg/m2 and weight equal or above 92 kg.
Side effects with the proposed patch may be of concern: In the clinical trial, about 40% of women reported unscheduled vaginal bleeding after 13 cycles of treatment.3
The FDA extended its review of the patch’s New Drug Application from Nov. 16, 2019, to Feb. 16, 2020. The review extension was issued after Agile Therapeutics submitted additional information to the FDA following the Oct. 30, 2019, committee meeting.
Will Patch Use Catch Up?
Combined oral contraceptives remain the most widely used combined hormonal contraceptive product in women of reproductive age in the retail setting nationwide. Data indicate that current use of the transdermal system is low, and prescription estimates have fallen steadily since 2006.
In 2018, an estimated 12.7 million patients filled combined hormonal prescriptions at retail pharmacies. About 36% were age 25-34 years, followed by women ages 17-24 years (35%), 35 years or older (25%), and teens age 16 years or younger (5%). Data indicate that the transdermal system accounted for 3.5% of use among teens age 16 or younger, and 3% or less among patients age 17 years or older.3
Patch use may have fallen off with concerns about its use and risk of venous thromboembolism (VTE). Labeling for the original transdermal contraceptive, Ortho Evra, was edited to address issues relating to VTE risk and exposure to contraceptive hormones as compared to combined oral contraceptives. In March 2011, the boxed warning was edited to include information about the potential risk of VTE, and the pharmacokinetics profile of ethinyl estradiol associated with the Evra patch, which made it more prominent to healthcare providers. Janssen Pharmaceuticals discontinued production in 2014; Mylan received FDA approval to market a generic version in the same year.
REFERENCES
- Kaunitz AM, Portman D, Westhoff CL, et al. Low-dose levonorgestrel and ethinyl estradiol patch and pill: A randomized controlled trial. Obstet Gynecol 2014;123:295-303.
- Mansour D. International survey to assess women’s attitudes regarding choice of daily versus nondaily female hormonal contraception. Int J Womens Health 2014;6:367-375.
- Food and Drug Administration. FDA Briefing Document NDA 204017 levonorgestrel and ethinyl estradiol transdermal system. Presented at the Bone, Reproductive, and Urologic Drugs Advisory Committee (BRUDAC) Meeting, Oct. 30, 2019. Available at: https://bit.ly/2RNpgMj.
- Vahratian A. Prevalence of overweight and obesity among women of childbearing age: Results from the 2002 National Survey of Family Growth. Matern Child Health J 2009;13:268-273.
Twirla, an investigational combined hormonal contraceptive patch, is under review by the FDA. In an October 2019 meeting, the patch received a 14 to 1 vote from the FDA’s Bone, Reproductive, and Urologic Drugs Advisory Committee.
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