Six-Year, Multi-Center, Pivotal Clinical Trial Data of LILETTA® (levonorgestrel-releasing intrauterine system) 52 mg Presented at 2019 ACOG Meeting
SAN FRANCISCO and DUBLIN, May 6, 2019 /PRNewswire/ -- Medicines360, a nonprofit women's health pharmaceutical company with a mission of expanding access to quality medicines, and Allergan plc (AGN), a leading global pharmaceutical company, presented new six-year data from Medicines360's 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) 2019 Annual Clinical and Scientific Meeting in Nashville, Tenn.
Investigators shared six-year pregnancy rates (by Pearl Index and life-table analysis) and safety outcomes from the ongoing ACCESS IUS (A Comprehensive Contraceptive Efficacy and Safety Study of an IUS) trial, the largest ongoing Phase 3 clinical trial of an IUS in the United States. The Pearl Index in the first year was 0.15 among women who were 16 to 35 years old when they enrolled in the study. At six years, the cumulative life-table pregnancy rate was 0.87. LILETTA is currently approved for up to five years for the prevention of pregnancy. The U.S. Food and Drug Administration (FDA) is currently reviewing an application requesting approval of LILETTA for up to six years of use based on data from ACCESS IUS.
The ACCESS IUS trial evaluates a diverse population of women: women aged 16 to 45, women who have and have not given birth, as well as obese and non-obese women. Data from women in the U.S. ranging in ages from 16 to 45 years were collected throughout the study. Women aged 36 to 45 received the IUS for safety evaluation only.
Two perforations following IUS placement were diagnosed within the first year, and no additional perforations have been reported in the trial to date. Expulsion occurred in 68 participants (4.0 percent). Most expulsions (73.5 percent) were diagnosed during the first year, with two diagnosed in year six. Pelvic infection was diagnosed in 15 women (0.9 percent), with most occurring (73.3 percent) after six or more months of use. Forty women (2.3 percent) discontinued due to bleeding complaints. Three quarters of these discontinuations (75.0 percent) occurred in the first two years.
"Our mission is to increase access to effective contraception for all appropriate women. These latest clinical findings from ACCESS IUS are encouraging as they further reinforce LILETTA's effectiveness and safety for pregnancy prevention in a broad range of women," said Jessica Grossman, M.D., CEO of Medicines360. "These data were included in our recent U.S. regulatory submission requesting approval of LILETTA for up to six years of use."
The poster was presented by Carolyn Westhoff, MD, MSC, Chief, Division of Family Planning, Sarah Billinghurst Solomon Professor of Reproductive Health, Department of Obstetrics and Gynecology, Professor of Population and Family Health and Epidemiology, Columbia University, on Saturday, May 4, 2019.
LILETTA® is a sterile, levonorgestrel-releasing intrauterine system indicated for prevention of pregnancy for up to 5 years. The system should be replaced after 5 years if continued use is desired.
IMPORTANT SAFETY INFORMATION
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 or endometritis
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.
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 also occur at any time during use. 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 4 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 (18.6%), vulvovaginal mycotic infections (18.6%), acne (14.9%), nausea or vomiting (9.8%), dyspareunia (9.1%), headache (8.9%), breast tenderness or pain (8.3%), pelvic discomfort or pain (8.3%), anxiety (8.1%), abdominal discomfort or pain (7.8%), depression (6.9%), dysmenorrhea (6.1%), mood changes (5.8%), increased weight (5.7%), back pain (5.5%), and vaginal discharge (5.4%).
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 health care 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. 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.
Allergan plc (AGN), headquartered in Dublin, Ireland, is a bold, global pharmaceutical leader. 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 primarily focused on four key therapeutic areas including medical aesthetics, eye care, central nervous system and gastroenterology.
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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.
Statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Allergan's current perspective on existing trends and information as of the date of this release. Actual results may differ materially from Allergan's current expectations depending upon a number of factors affecting Allergan's business. These factors include, among others, the difficulty of predicting the timing or outcome of FDA approvals or actions, if any; the impact of competitive products and pricing; market acceptance of and continued demand for Allergan's products; the impact of uncertainty around timing of generic entry related to key products, including RESTASIS®, on our financial results; risks associated with divestitures, acquisitions, mergers and joint ventures; risks related to impairments; uncertainty associated with financial projections, projected cost reductions, projected debt reduction, projected synergies, restructurings, increased costs, and adverse tax consequences; difficulties or delays in manufacturing; and other risks and uncertainties detailed in Allergan's periodic public filings with the Securities and Exchange Commission, including but not limited to Allergan's Annual Report on Form 10-K for the year ended December 31, 2018. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.
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