EXECUTIVE SUMMARY

Lyndra Therapeutics has received a $13 million grant from the Bill & Melinda Gates Foundation to develop a once-a-month oral contraceptive to provide women with a discreet, noninvasive, reversible option.

• Forgetting one to three pills per cycle is a frequent problem among 15-51% of users, particularly among adolescents. It is estimated that nine out of every 100 women will experience an unintended pregnancy within the first year of typical use of oral contraceptives.

• Scientists are developing a drug delivery platform that slowly releases medication in the stomach over a set period of time. This platform will help to make daily pills a thing of the past, researchers say.


Many scientific strides have been made in the past 25 years when it comes to combined oral contraceptives (OCs). Scientists have addressed the estrogen component, lowering the dose of ethinyl estradiol to reduce such side effects as bloating, breast tenderness, and nausea. Progestin doses, as well as associated endocrine and metabolic characteristics, also have changed. By improving originally manufactured progestins, such as those derived from 19-nor-progesterone, and developing new progestins, side effects such as acne and effects on high-density lipoprotein cholesterol levels have been reduced.1,2

Although lowering side effects plays an important role in oral contraceptive compliance, one of the biggest challenges for patients is adhering to the daily schedule of the pill. Forgetting one to three pills per cycle is a frequent problem among 15-51% of users, particularly among adolescents.3 It is estimated that nine out of every 100 women will experience an unintended pregnancy within the first year of typical use of oral contraceptives.4

Lyndra Therapeutics has received a $13 million grant from the Bill & Melinda Gates Foundation and is setting out to remove the daily pill compliance challenge. The company is in early development of a monthly oral contraceptive to provide women with a discreet, noninvasive, reversible contraception option.

“This grant is special because it extends our focus on meeting unmet therapeutic need into women’s health,” said Amy Schulman, JD, chief executive officer and co-founder of Lyndra Therapeutics, in a statement. “We are proud to be part of the foundation’s effort to improve lives and ensure better health outcomes by making it easier to access and benefit from family planning.” (View the statement online at: https://bit.ly/2ztNEIx.)

Changing the Mechanics

Lyndra Therapeutics is developing a drug delivery platform that slowly releases medication in the stomach over a set period of time. This platform will help to make daily pills a thing of the past, according to company officials.

All current commercially available gastric resident dosage forms, and most in development, are limited to gastric residence of less than one day, according to Lyndra Therapeutics researchers.5 The company is partnering with Gilead Sciences to develop and commercialize ultra-long-acting oral HIV therapies. Gilead’s anti-HIV drug combination, Truvada, is the cornerstone of pre-exposure prophylaxis (PrEP) against HIV. The U.S. Preventive Services Task Force now recommends that PrEP be offered to all people at high risk of HIV.6,7

Lyndra’s technology is based on a star-shaped structure with six arms, loaded with drug molecules. The arms fold inward, encasing the structure in a smooth capsule. After the capsule is swallowed, stomach acid dissolves the capsule’s outer layer, unfolding the arms and releasing its drug molecules. Once the structure is expanded, it is large enough to stay in the stomach and resist being pushed down the digestive tract without blocking other items. Its arms are designed to break off eventually so that all pieces are expelled naturally.

Scientific tests in pigs indicate that a pill with such a structure could continue to release medicine in the stomach for two weeks.8 Lyndra scientists are developing new versions of the capsule to provide one dose per month.

Researchers will conduct preclinical evaluation of the oral contraceptive in collaboration with Routes2Results, a nonprofit social and public health research organization based in the United Kingdom, through additional funding from the Gates Foundation. The foundation also awarded Lyndra Therapeutics a grant to develop a long-acting malaria drug. The company is using recently raised funding for Phase II clinical trials, expansion of its Phase I pipeline, and manufacturing scale-up.

Will Women Use It?

Family planning clinicians seek to offer women the full range of contraceptive options in an effort for birth control success. As Contraceptive Technology points out, “the best method of contraception for an individual is one that is safe and that will actually be used correctly and consistently.”9

Use of methods such as the contraceptive injectable, the vaginal contraceptive ring, and the transdermal contraceptive patch has grown over the past 20 years. The number of women who receive the injection grew from 5% in 1995 to 23% in 2006-2010. Ever-use of the contraceptive patch grew from less than 1% in 2002 to 10% in 2006-2010. Six percent of women in 2006-2010 reported using the contraceptive ring.10

In 2014, about 14% of women using a contraceptive reported using a long-acting reversible contraceptive (LARC) method — 12% used intrauterine devices, while 3% used the contraceptive implant.11 Use of LARCs has grown from 2% in 2002 to 6% in 2007 and 9% in 2009.12,13

The increase in LARC usage has come in part due to the success of research demonstrating its effect on unintended pregnancy and abortion. In the Contraceptive CHOICE project, 9,256 women ages 14-45 years were offered their choice of contraceptive method without charge. About 75% of women chose long-acting methods, with significant results. The project identified a notable reduction in unintended pregnancies and abortion rates of study participants compared with a similar population from the same geographic area.14 In the Zika Contraception Access Network (Z-CAN) — a program designed to prevent unintended pregnancies and reduce birth defects during the height of the 2016-2017 Zika virus outbreak in Puerto Rico — 67.5% of 21,124 women chose and received a LARC method at their initial visit.15 In the Colorado Family Planning Initiative, investigators provided access to LARCs at no cost to clients in Title X-funded clinics in 37 of Colorado’s 64 counties. Data indicate LARC use increased from 5% to 19% among low-income teenagers and young women. The increase in LARC use was accompanied by decreases in birth rates and abortion rates in both age brackets, results indicated.16

REFERENCES

  1. De Leo V, Musacchio MC, Cappelli V, et al. Hormonal contraceptives: Pharmacology tailored to women’s health. Hum Reprod Update 2016;22:634-646.
  2. Gebel Berg E. The chemistry of the pill. ACS Cent Sci 2015;1:5-7.
  3. Chabbert-Buffet N, Jamin C, Lete I, et al. Missed pills: Frequency, reasons, consequences and solutions. Eur J Contracept Reprod Health Care 2017;22:165-169.
  4. Trussell J. Contraceptive failure in the United States. Contraception 2011;83:397-404.
  5. Altreuter DH, Kirtane AR, Grant T, et al. Changing the pill: Developments toward the promise of an ultra-long-acting gastroretentive dosage form. Expert Opin Drug Deliv 2018;15:1189-1198.
  6. U.S. Preventive Services Task Force, Owens DK, Davidson KW, Krist AH, et al. Preexposure prophylaxis for the prevention of HIV Infection: U.S. Preventive Services Task Force recommendation statement. JAMA 2019;321:2203-2213.
  7. Chou R, Evans C, Hoverman A, et al. Preexposure prophylaxis for the prevention of HIV infection: Evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA 2019;321:2,214-2,230.
  8. Traverso G, Schoellhammer CM, Schroeder A, et al. Microneedles for drug delivery via the gastrointestinal tract. J Pharmaceutical Sci 2015;104:362-367.
  9. Guthrie KA, Trussell J. Choosing a contraceptive: Efficacy, safety, and personal considerations. In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 21st revised edition. New York. Ayer Company Publishers, 2018.
  10. 10. Daniels K, Mosher WD, Jones J. Contraceptive methods women have ever used: United States, 1982-2010. National Health Stat Report 2013;62:1-15.
  11. Kavanaugh ML, Jerman J. Contraceptive method use in the United States: Trends and characteristics between 2008 and 2014. Contraception 2018;97:14-21.
  12. Kavanaugh ML, Jerman J, Finer LB. Changes in use of long-acting reversible contraceptive methods among U.S. women, 2009-2012. Obstet Gynecol 2015;126:917-927.
  13. Finer LB, Jerman J, Kavanaugh ML. Changes in use of long-acting contraceptive methods in the United States, 2007-2009. Fertil Steril 2012;98:893-897.
  14. Peipert JF, Madden T, Allsworth JE, et al. Preventing unintended pregnancies by providing no-cost contraception. Obstet Gynecol 2012;120:1291-1297.
  15. Lathrop E, Romero L, Hurst S, et al. The Zika Contraception Access Network: A feasibility programme to increase access to contraception in Puerto Rico during the 2016-17 Zika virus outbreak. Lancet Public Health 2018;3:e91-e99.
  16. Ricketts S, Klingler G, Schwalberg R. Game change in Colorado: Widespread use of long-acting reversible contraceptives and rapid decline in births among young, low-income women. Perspect Sex Reprod Health 2014;46:125-132