EXECUTIVE SUMMARY

While the 20th century yielded new contraceptives in the form of pills, rings, patches, intrauterine devices, and implants, it is time for new exploration into further birth control options. The United Nations predicts that the human population will reach 9 billion by 2050, and almost 11.2 billion by the end of the century.

Evofem has resubmitted a New Drug Application for its contraceptive gel, Amphora. It uses lactic acid to maintain an acidic pH in the vagina, creating an environment hostile to sperm and bacteria.

The International Partnership for Microbicides has developed a vaginal ring containing the antiretroviral drug dapivirine and the contraceptive hormone levonorgestrel in an effort to provide protection against HIV/AIDS and unintended pregnancy. Results of an initial clinical trial noted no safety issues.


Brace for continued population growth: The United Nations predicted that the human population will reach 9 billion by 2050, and almost 11.2 billion by the end of the century.1 While the 20th century yielded new contraceptives in the form of pills, rings, patches, intrauterine devices, and implants, it is time for new exploration into further birth control options, said Deborah Anderson, PhD, professor of obstetrics/gynecology, microbiology, and medicine at Boston University School of Medicine. Anderson wrote a perspective on the matter in a recent issue of the New England Journal of Medicine.2

“With approximately 40% of pregnancies being unplanned, the time seems ripe for another contraception revolution to provide options for the diverse populations that are not currently being served by modern contraception,” Anderson said in a statement.3

Reproductive health clinicians may see a new contraceptive product in 2020, as San Diego-based Evofem has resubmitted a New Drug Application for its contraceptive gel, Amphora. It uses lactic acid to maintain an acidic pH in the vagina, creating an environment hostile to sperm and bacteria.

Amphora has been tested in a multicenter Phase III clincal trial. The Phase III AMPOWER study was designed as a confirmatory single-arm, open-label trial to evaluate the safety and efficacy of Amphora in 1,400 healthy women age 18-35 years. Top-line data analysis indicates a cumulative pregnancy rate of 14% over seven cycles of use (95% confidence interval [CI] 10.0-18.0). In women who correctly used Amphora, the cumulative pregnancy rate was 1.3% over seven cycles of use (95% CI 0.4-2.1).4

Amphora also is being tested for the prevention of urogenital Chlamydia trachomatis infection in women, and for the prevention of urogenital Neisseria gonorrhoeae infection in women. Scientists are evaluating its use in the prevention of recurrent bacterial vaginosis.

Science Focuses on Dapivirine

Researchers have developed a vaginal ring containing the antiretroviral drug dapivirine and the contraceptive hormone levonorgestrel to provide protection against HIV/AIDS and unintended pregnancy. The results of an initial clinical trial noted no safety issues.5

The Silver Spring, MD-based International Partnership for Microbicides is seeking regulatory approval of a 25 mg dapivirine vaginal ring, which would be the first biomedical HIV prevention method developed specifically for women. If approved, it would allow the European Medicines Agency, in cooperation with the World Health Organization, to provide a scientific opinion on the ring’s use in low- and middle-income countries. The ring also would provide an HIV prevention option besides oral pre-exposure prophylaxis (PrEP) Truvada, which consists of the anti-HIV drugs emtricitabine and tenofovir disoproxil fumarate. Truvada is the only medication currently approved for HIV PrEP.

The need for a means of HIV prevention controlled by women is great. Despite impressive strides in prevention and treatment, AIDS-related illnesses remain the leading cause of death worldwide among women of reproductive age.6

Scientists are investigating Ovaprene, a nonhormonal monthly ring, as a potential contraceptive. Ovaprene is designed to work through a combination of a permeable mesh in the center of the ring that creates a partial barrier to sperm, with the ring’s release of locally acting spermiostatic agents to create an inhospitable environment for sperm. Daré Bioscience has received a grant providing up to $1.9 million for research of the ring from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

New Study Shows Promise

Daré Bioscience initiated a postcoital clinical trial in 2018 to assess general safety and effectiveness in preventing sperm from reaching the cervical canal following intercourse. Initial topline results indicate that the device prevented almost all sperm from entering the cervical canal, a surrogate marker for highly effective contraception. Daré Bioscience officials say data from this study will be used to support an investigational device exemption filing with the Center for Devices and Radiological Health at the FDA. If approved, the company plans to initiate a pivotal contraceptive effectiveness and safety study of Ovaprene in the second half of 2020.7

Currently available contraceptive rings offer effectiveness rates that are similar or slightly better than the pill, ease of use without the need to remember a daily routine, and user ability to control initiation and discontinuation.8 Two contraceptive rings are available in the United States: Annovera and NuvaRing. Annovera is a soft, reusable, flexible silicone ring containing segesterone acetate and ethinyl estradiol. Left in place for 21 days and removed for seven days each cycle, it is indicated to prevent pregnancy for up to a year. Clinicians are more familiar with NuvaRing, which was approved in 2001. NuvaRing releases a combination of etonogestrel and ethinyl estradiol from a ring made of ethylene-vinyl acetate copolymers. Each ring is designed for three weeks of continuous use, with a one-week break, followed by insertion of a new ring.

Topical Treatment Under Microscope

Researchers at the Boston University School of Medicine and Mapp Biopharmaceutical, Inc. are leading a new Contraceptive Research Center funded by an $8 million grant from the NICHD. Through this consortium of academic and for-profit entities, scientists are examining a topical antisperm monoclonal antibody as a basis for contraception methods. Antibodies against sperm commonly occur in infertility patients; scientists believe such antibodies may cause infertility due to sperm agglutination and mucus trapping.

Researchers also are developing a contraceptive antibody formulated into a vaginal film that will be tested for safety in toxicology studies. If successful, the film will be tested for safety and efficacy in Phase I clinical trials.

Due to their versatility, specificity, and safety profile, monoclonal antibodies may serve as candidates for multipurpose prevention technology (MPT) that block both pregnancy and sexually transmitted infections. A contraceptive antibody could be used alone or in combination with antibodies directed against sexually transmitted pathogens to enhance the acceptability, efficacy, and marketability of contraceptive MPT products.

REFERENCES

  1. United Nations Department of Economic and Social Affairs, Population Division. World Population Prospects 2019: Highlights. New York City; 2019.
  2. Anderson DJ. Population and the environment — time for another contraception revolution. N Engl J Med 2019;381:397-399.
  3. Boston University School of Medicine. BU researcher asks, ‘Is it time for another contraception revolution?’ July 18, 2019. Available at: https://bit.ly/2RMPxuu.
  4. Evofem Biosciences. Evofem Biosciences announces positive top-line results of phase 3 study evaluating Amphora for hormone-free birth control. Dec. 17, 2018. Available at: https://prn.to/2EfHvly.
  5. Achilles S. Safety and pharmacokinetics of dapivirine and levonorgestrel vaginal rings for multipurpose prevention of HIV and pregnancy. Presented at the HIV Research for Prevention conference, Madrid, October 2018.
  6. UNAIDS. Global AIDS Monitoring 2017: Indicators for monitoring the 2016 United Nations Political Declaration on HIV and AIDS. Geneva: UNAIDS, 2017.
  7. Daré Bioscience. Daré Bioscience announces positive findings from a postcoital test clinical study of Ovaprene hormone-free contraceptive candidate. Nov. 12, 2019. Available at: https://bit.ly/34l7ZwZ.
  8. Brache V, Payán LJ, Faundes A. Current status of contraceptive vaginal rings. Contraception 2013; 87:264-272.