Medicines360 and Allergan Present Five-Year Multi-Center Pivotal Clinical Trial Data of LILETTA® (levonorgestrel-releasing intrauterine system) 52 mg at 2018 ACOG Meeting
SAN FRANCISCO and DUBLIN – Medicines360, a nonprofit women’s health pharmaceutical company with a mission of expanding access to quality medicines, and Allergan plc (NYSE: AGN), a leading global pharmaceutical company, presented five-year data from their ongoing multi-center U.S.-based pivotal clinical trial investigating its intrauterine system (IUS), LILETTA® (levonorgestrel-releasing intrauterine system) 52 mg, at the American College of Obstetricians and Gynecologists (ACOG) 2018 annual clinical and scientific meeting in Austin, Texas. The abstract presents five-year pregnancy rates (by Pearl Index and life-table analysis) and safety outcomes from the ongoing study. The Pearl Index in the first year, among women who were 16–35 years old when they enrolled in the study, was 0.15 (CI: 0.02, 0.55). The cumulative life-table pregnancy rate at 5 years was 0.92 (CI: 0.46,1.84).
LILETTA is currently approved for up to four years for the prevention of pregnancy. Data from women in the U.S. ranging in ages from 16–45 years were collected throughout the study. Women aged 36–45 received the IUS for safety evaluation only. The study collects data from a variety of women, ranging from women in their late teens to those in their mid-forties, obese and non-obese women, as well as women that have not previously given birth and those who have.
Perforation following IUS placement occurred in two (0.1%) women; both were diagnosed within the first year. Expulsion was reported in 63 (3.7%) participants, and most (50 [79.4%]) occurred during the first year of use. Pelvic infection was diagnosed in 11 (0.6%) women. There were 39 (2.3%) women who discontinued due to bleeding complaints over 5 years.
“We are encouraged by the presentation today at ACOG, which represents the data from our ongoing clinical trial used in our recent submission to the FDA requesting approval of LILETTA for up to five years of use. This will in turn help us deliver on our mission of providing appropriate women of all socioeconomic levels the option of an effective long-acting reversible contraception,” said CEO of Medicines360, Jessica Grossman, MD.
The poster presentation “Five-year efficacy and safety of the LILETTA® levonorgestrel intrauterine system” was presented by Dr. Thomas D. Kimble, M.D., Eastern Virginia Medical School, Norfolk, VA; on Saturday, April 28.
LILETTA® is a sterile, levonorgestrel-releasing intrauterine system indicated for prevention of pregnancy for up to 4 years. The system should be replaced after 4 years if continued use is desired.
Important Safety Information
(scroll to see additional Important Safety Information and full Prescribing Information link)
Who is not appropriate for LILETTA®
Use of LILETTA is contraindicated in women with: known or suspected pregnancy and cannot be used for post-coital contraception; congenital or acquired uterine anomaly, including fibroids, if they distort the uterine cavity and would be incompatible with correct IUS placement; known or suspected breast cancer or other hormone-sensitive cancer, now or in the past; known or suspected uterine or cervical neoplasia; acute liver disease or liver tumors; untreated acute cervicitis or vaginitis, including lower genital tract infections (eg, bacterial vaginosis) until infection is controlled; infected abortion in the past 3 months; unexplained uterine bleeding; current IUS; acute pelvic inflammatory disease (PID) or endometritis or history of PID (except with later intrauterine pregnancy); conditions increasing susceptibility to pelvic infection; or hypersensitivity to any component of LILETTA.
Clinical considerations for use and removal of LILETTA®
Use LILETTA with caution after careful assessment in patients with coagulopathy or taking anticoagulants; migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia; exceptionally severe or frequent headache; marked increase of blood pressure; or severe arterial disease such as stroke or myocardial infarction. Consider removing LILETTA if the following arise during use: uterine or cervical malignancy or jaundice. Because irregular bleeding/spotting is common during the first months of LILETTA use, exclude endometrial pathology (polyps or cancer) prior to the insertion of LILETTA in women with persistent or uncharacteristic bleeding. If the threads are not visible or are significantly shortened, they may have broken or retracted into the cervical canal or uterus. If LILETTA is displaced (eg, expelled or perforated the uterus), remove it.
Pregnancy related risks with LILETTA®
If pregnancy should occur with LILETTA in place, remove the intrauterine system because leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal or manipulation may result in pregnancy loss. Evaluate women for ectopic pregnancy because the likelihood of a pregnancy being ectopic is increased with LILETTA. Tell women about the signs of ectopic pregnancy and associated risks, including loss of fertility. Women with a history of ectopic pregnancy, tubal surgery, or pelvic infection carry a higher risk of ectopic pregnancy.
Educate her about PID
Insertion of LILETTA is contraindicated in the presence of known or suspected PID or endometritis or a history of PID unless there has been a subsequent intrauterine pregnancy. IUSs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. One woman diagnosed with PID developed the infection within a week of LILETTA insertion, while the remainder were diagnosed more than six months after insertion. Counsel women who receive LILETTA to notify a healthcare provider if they have complaints of lower abdominal or pelvic pain, odorous discharge, unexplained bleeding, fever, or genital lesions or sores. PID and endometritis are often associated with sexually transmitted infections (STIs); LILETTA does not protect against STIs, including HIV. PID or endometritis may be asymptomatic but still result in tubal damage and its sequelae. Inform women about the possibility of PID or endometritis and that these infections can cause tubal damage leading to ectopic pregnancy or infertility, or infrequently can necessitate hysterectomy, or cause death.
Expect changes in bleeding patterns with LILETTA
Spotting and irregular or heavy bleeding may occur during the first 3 to 6 months. Periods may become shorter and/or lighter thereafter. Cycles may remain irregular, become infrequent, or even cease. Consider pregnancy if menstruation does not occur within 6 weeks of the onset of previous menstruation. If a significant change in bleeding develops during prolonged use, take appropriate diagnostic measures to rule out endometrial pathology. If a significant change in bleeding develops during prolonged use, take appropriate diagnostic measures to rule out endometrial pathology.
Be aware of other serious complications and most common adverse reactions
Some serious complications with IUSs like LILETTA are sepsis, perforation, and expulsion. Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of other LNG-releasing IUSs. Aseptic technique during insertion of LILETTA is essential to minimize serious infections such as GAS.
Perforation (total or partial, including penetration/embedment of LILETTA in the uterine wall or cervix) may occur, most often during insertion, although the perforation may not be detected until sometime later. Perforation may reduce contraceptive efficacy. If perforation is suspected, locate and remove LILETTA as soon as possible. Surgery may be required. Delayed detection or removal of LILETTA in case of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses, and erosion of adjacent viscera. The risk of perforation is higher if inserted in lactating women and may be higher if inserted in women who are postpartum or when the uterus is fixed retroverted.
Partial or complete expulsion of LILETTA may occur, resulting in the loss of contraceptive protection.
Delay LILETTA insertion a minimum of 6 weeks or until uterine involution is complete following a delivery or a second trimester abortion. Remove a partially expelled LILETTA. If expulsion has occurred, a new LILETTA may be inserted within 7 days after the onset of a menstrual period after pregnancy has been ruled out.
Ovarian cysts may occur and are generally asymptomatic, but may be accompanied by pelvic pain or dyspareunia. Evaluate persistent ovarian cysts.
In the LILETTA clinical trial, the most common adverse reactions (≥5% users) were vaginal bacterial infections (17.9%), vulvovaginal mycotic infections (17.9%), acne (14.5%), nausea or vomiting (9.4%), dyspareunia (8.8%), headache (8.7%), breast tenderness or pain (8.0%), pelvic discomfort or pain (7.9%), anxiety (7.6%), abdominal pain or discomfort (7.4%), depression (6.4%), increased weight (5.6%), dysmenorrhea (5.6%), mood changes (5.5%), vaginal discharge (5.3%), and back pain (5.2%).
Teach patients to recognize and immediately report signs or symptoms of the aforementioned conditions. Evaluate patients 4 to 6 weeks after insertion of LILETTA and then yearly or more often if clinically indicated.
Please see full Prescribing Information.
Medicines360, located in San Francisco, California, is a nonprofit global women’s health pharmaceutical company with a mission to expand access to quality medicines for all women regardless of their socioeconomic status, insurance coverage, or geographic location. Medicines360 is committed to working with healthcare providers, advocacy groups and patients to deliver innovative and meaningful treatments that help women around the world have greater access to the medicines they need. For more information, visit www.medicines360.org.
About Allergan Women’s Healthcare
Allergan is a leader in women’s healthcare that is dedicated to developing and commercializing best-in-class pharmaceuticals to improve the health and wellness of women. Allergan takes a holistic and a best-in-class approach to women’s healthcare as it prioritizes educational partnerships with OB/GYNs and advocacy groups. The mission of Allergan Women’s Healthcare extends beyond its pharmaceutical products to ensure that all women can make informed decisions about their health and have access to high-quality medications. Allergan is committed to investing in programs that support the education and well-being of all women.
About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global pharmaceutical company and a leader in a new industry model – Growth Pharma. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine products for patients around the world.
Allergan markets a portfolio of leading brands and best-in-class products for the central nervous system, eye care, medical aesthetics and dermatology, gastroenterology, women’s health, urology and anti-infective therapeutic categories.
Allergan is an industry leader in Open Science, a model of research and development, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. With this approach, Allergan has built one of the broadest development pipelines in the pharmaceutical industry.
Allergan’s success is powered by our global colleagues’ commitment to being Bold for Life. Together, we build bridges, power ideas, act fast and drive results for our customers and patients around the world by always doing what is right.
With commercial operations in approximately 100 countries, Allergan is committed to working with physicians, healthcare providers and patients to deliver innovative and meaningful treatments that help people around the world live longer, healthier lives every day.
For more information, visit Allergan’s website at www.Allergan.com.
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