Executive Summary

Scientists are looking at development of longer-acting injectable contraceptives. More than 40 million women worldwide use injectable contraceptives to prevent pregnancy.

  • Injectables on the global market are effective for 1-3 months, depending on the formulation. Such shots require women to return to providers 4-12 times per year. An important reason for discontinuation of the method is missed reinjections.
  • With funding from the Bill & Melinda Gates Foundation, FHI 360 has launched a project to support early testing of innovative approaches toward the goal of developing an injectable contraceptive that would last for six months. The selected four candidates look at different methods of drug delivery, including microspheres, microparticles, and polymeric suspension.

With the trend toward increased use of long-acting reversible contraceptives (LARCs) such as the intrauterine device and contraceptive implant, science is looking at development of longer-acting injectable contraceptives.1 More than 40 million women worldwide use injectable contraceptives to prevent pregnancy.2

While LARCs offer top-tier effectiveness, for many women around the world, they are unaffordable or don’t meet individual needs or preferences.3 New reversible injectable products with durations between the three-month injectable contraceptives and the contraceptive implants and intrauterine devices would fill an important gap in the existing contraceptive method mix and would increase choices for women, say researchers.1

Injectables on the global market are effective for 1-3 months, depending on the formulation. These injectables therefore require women to return to providers 4-12 times per year. An important reason for discontinuation of the method is missed reinjections, says Vera Halpern, MD, scientist at FHI 360 in Durham, NC.

“Women find it difficult to comply with reinjection schedules whether it is difficult because they forget or it is difficult for them to get to the clinical facility in time, especially in areas where the access is not simple or easy,” notes Halpern, who served as the lead author of a current analysis on development of longer-acting injectables. “An injection that would last longer and require less frequent visits for reinjection seems like a very good option to have in the method mix, and it does not exist.”

According to the table of U.S. contraceptive effectiveness/continuation rates in Contraceptive Technology, depot medroxyprogesterone acetate (DMPA, Depo Provera, Pfizer, New York City) has the lowest continuation rate of all modern contraceptives; 56% of women continue use of the method at the end of the first year.4

Research in the pipeline

With funding from the Bill & Melinda Gates Foundation of Seattle, FHI 360 has launched a project to support early testing of innovative approaches toward the goal of developing an injectable contraceptive that would last for six months. This project is a first step toward bringing a game-changing injectable contraceptive to market, says FHI 360.

In 2012, FHI 360 issued a Request for Proposals for proof-of-concept testing of candidates that have the potential to be developed into a longer-acting injectable. Proposals were received from lead drug delivery research groups in the United States, Europe, India, and China, and represented a wide range of innovative approaches. (Contraceptive Technology Update reported on the search. See “Longer-acting method that is injectable probed,” March 2013, and “The search has begun for long-acting contraceptives,” December 2013.)

Four proposals were selected to move forward for proof-of-concept testing and are collecting data in support of this initiative:

  • poly(lactide) and poly-lactic-co-glycolic acid microspheres releasing levonorgestrel, (Shanghai [China] Institute of Planned Parenthood Research);
  • poly-lactic-co-glycolic acid microspheres releasing etonogestrel, (Orbis Biosciences in Kansas City);
  • nanostructured porous silicon microparticles releasing various contraceptive steroids, (University of California, San Diego in La Jolla);
  • a biodegradable polymeric gel formulation releasing levonorgestrel, (University of Tennessee Health Science Center in Memphis).

The goal is to develop and bring to market a six-month injectable within 10-15 years and possibly sooner, say researchers.1

Longer duration desired

Previous investigations have shown that injectable contraceptives with a longer interval between injections lead to better adherence and continuation rates when compared to those with shorter intervals, notes Halpern.

A study that looked at the three-month injectable depot medroxyprogesterone acetate and one-month injectable medroxyprogesterone acetate/estradiol cypionate (Cyclofem, not available in the United States) found that the one-year continuation rate was higher for the longer-acting drug.5 The main difference stated by study participants was logistical difficulty in making frequent clinic visits. In a study comparing DMPA 150 mg given every three months versus DMPA 450 mg given every six months, findings indicate a significantly better acceptability of the six-month regimen, primarily due to convenience and reduced travel costs.6 Research on the acceptability of longer-acting injectables in other therapeutic areas also points to acceptability of a longer-acting shot, notes Halpern.7

“That’s our main rationale and reason for investing in developing a longer-acting injectable contraceptive,” says Halpern. “We think that compliance will be better and, therefore, the effectiveness will be better.”

REFERENCES

  1. Halpern V, Stalter RM, Owen DH, et al. Towards the development of a longer-acting injectable contraceptive: Past research and current trends. Contraception2015; doi:doi.org/10.1016/j.contraception.2015.02.014.
  2. United Nations Department of Economic and Social Affairs, Population Division. World Contraceptive Use. Accessed at http://bit.ly/1JvErN6.
  3. Darroch JE, Sedgh G, Ball H. Contraceptive Technologies: Responding to Women’s Needs. New York: Guttmacher Institute; 2011.
  4. Trussell J, Guthrie KA. Choosing a contraceptive: Efficacy, safety and personal considerations. In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 20th revised edition. New York: Ardent Media; 2011.
  5. Ruminjo JK, Sekadde-Kigondu CB, Karanja JG, et al. Comparative acceptability of combined and progestin-only injectable contraceptives in Kenya. Contraception 2005; 72:138-145.
  6. Castle WM, Sapire KE, Howard KA. Efficacy and acceptability of injectable medroxyprogesterone. A comparison of 3-monthly and 6-monthly regimens. S Afr Med J1978; 53:842-845.
  7. Abouelfadel Z, Crawford ED. Leuprorelin depot injection: Patient considerations in the management of prostatic cancer. Ther Clin Risk Manag 2008; 4:513-526.

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