Largest Phase 3 Pivotal Hormonal IUD Trial Conducted Exclusively in U.S. Supports FDA Approval of LILETTA for Women
DUBLIN and SAN FRANCISCO – Actavis plc (NYSE: ACT), a leading global pharmaceutical company and leader in women’s health care, and Medicines360, a nonprofit women’s health pharmaceutical company, announced that the initial results of ACCESS IUS (A Comprehensive Contraceptive Efficacy and Safety Study of an IUS) were published online today in the medical journal Contraception.
The study found that LILETTA™ (levonorgestrel-releasing intrauterine system) 52 mg, is 99.45% effective for the prevention of pregnancy for up to three years of use in women aged 16-35 regardless of race, parity (previous births), or body mass index (BMI). The ACCESS IUS trial is still ongoing and will evaluate the efficacy and safety of LILETTA for up to seven years of use.
“The rate of unintended pregnancy in the U.S. remains unacceptably high at more than 50% and is even higher amongst women with lower incomes. Only a small percentage of contracepting women (7.7%) are using IUDs which are among the most effective methods. Importantly, not all women have been able to access IUDs due to lack of awareness and cost barriers,” said Mitchell Creinin, MD, Professor and Director of Family Planning in the Department of Obstetrics and Gynecology at the University of California, Davis and senior author of the published study report.
The multicenter clinical trial was conducted by Medicines360 and is the first and only FDA-approval study for an IUD conducted exclusively in the U.S. ACCESS IUS was performed at 29 sites including public health clinics, private offices and University centers The study enrolled 1,751 women aged 16-45, including nearly 60% who had not previously given birth (nulliparous), the largest group of such women ever included in an IUD approval study. Demographics mirrored the 2010 U.S. census; most women were Caucasian (78.4%) or Black/African American (13.3%), and 14.7% were of Hispanic ethnicity. The study had no upper BMI limit for enrollment and 25% of participants were obese.
The primary study outcome was pregnancy rate in women aged 16-35 years. Pregnancies occurred in two nulliparous (never given birth) and four parous (previously given birth) participants. The pregnancy rate (measured as a Pearl Index) for LILETTA was 0.15 (95% CI 0.02, 0.55) per 100-women years during year one and 0.22 (95% CI 0.08, 0.49) per 100-women years through year three. The cumulative life-table pregnancy rate was 0.55 (95% CI 0.24, 1.23) through 3 years.
The most common adverse events leading to discontinuation were expulsion (3.5%), bleeding complaints (1.5%), acne (1.3%) and mood swings (1.3%). Most expulsions occurred in the first year, consistent with expulsion timing seen with other IUDs. Of the 68 women followed for fertility after LILETTA discontinuation, 48 (70.6%) conceived spontaneously within six months and 59 (86.8%) within 12 months; the median time to conception was four months.
“ACCESS IUS underscores the importance of increasing our knowledge of the benefits of IUDs and for expanding access to one of the most effective, reversible and well-tolerated forms of birth control for women,” said Kathleen Reape, MD, Senior Vice President, Clinical Development, Global Brands R&D, Actavis. “With our partner Medicines360, we’re proud to make newly-launched LILETTA accessible to all IUD-appropriate women through their health care provider, including public health clinics enrolled in the 340B Drug Pricing Program. Now, more women will have more choices for highly effective contraception.”
About LILETTA™
LILETTA is a small, flexible plastic T-shaped system which is 32 mm x 32 mm in size. It works to prevent pregnancy by slowly releasing levonorgestrel (LNG), a progestin, at an initial release rate of 18.6 mcg/day with an average in vivo release rate of LNG of approximately 15.6 mcg/day over a period of three years. Generally, LILETTA can be inserted at any time if the provider is reasonably certain that the woman is not pregnant. While LILETTA is intended for use up to three years, it can be removed by a healthcare professional at any time. LILETTA can be replaced at the time of removal with a new LILETTA, if continued contraceptive protection is desired.
LILETTA™ 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; known or suspected breast cancer or other progestin-sensitive cancer, now or in the past; known or suspected uterine or cervical neoplasia; liver disease, including tumors; untreated acute cervicitis or vaginitis, including lower genital tract infections (eg, bacterial vaginosis) until infection is controlled; postpartum endometritis or infected abortion in the past 3 months; unexplained uterine bleeding; current IUD; acute pelvic inflammatory disease (PID) 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 headache; marked increase of blood pressure; or severe arterial disease such as stroke or myocardial infarction. Consider removing the intrauterine system if these or the following arise during use: uterine or cervical malignancy or jaundice. If LILETTA™ is displaced (e.g., 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
IUDs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. Inform women about the possibility of PID and that PID can cause tubal damage leading to ectopic pregnancy or infertility, or infrequently can necessitate hysterectomy, or cause death. PID is often associated with sexually transmitted infections (STIs); LILETTA™ does not protect against STIs, including HIV.
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.
Be aware of other serious complications and most common adverse reactions
Some serious complications with IUDs like LILETTA™ are expulsion, sepsis, and perforation. Perforation may reduce contraceptive efficacy. The risk of perforation is higher if inserted in lactating women and may be higher if inserted in women who are less than 6 weeks postpartum or when the uterus is fixed retroverted.
Ovarian cysts may occur and are generally asymptomatic, but may be accompanied by pelvic pain or dyspareunia. Evaluate persistent ovarian cysts.
In clinical trials of LILETTA™ the most common adverse reactions (≥5% users) are vaginal infections (13.6%), vulvovaginal infections (13.3%), acne (12.3%), headache or migraine (9.8%), nausea or vomiting (7.9%), dyspareunia (7.0%), abdominal discomfort or pain (6.8%), breast tenderness or pain (6.7%), pelvic discomfort or pain (6.1%), depression or depressed mood (5.4%) and mood changes (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.
About Medicines360
Medicines360 is an innovative nonprofit global women’s health pharmaceutical company with a mission to expand access to medicines for all women regardless of their socioeconomic status, insurance status, or geographic location. By partnering with pharmaceutical companies, Medicines360 will demonstrate that taking a socially responsible approach is good for business. For more information, visit www.medicines360.org.
About Actavis
Actavis plc (NYSE: ACT), headquartered in Dublin, Ireland, is a unique, global pharmaceutical company and a leader in a new industry model – Growth Pharma. Actavis is focused on developing, manufacturing and commercializing innovative branded pharmaceuticals, high-quality generic and over-the-counter medicines and biologic products for patients around the world.
Actavis markets a portfolio of best-in-class products that provide valuable treatments for the women’s health, central nervous system, eye care, medical aesthetics, gastroenterology, urology, cardiovascular and anti-infective therapeutic categories, and operates the world’s third-largest global generics business, providing patients around the globe with increased access to affordable, high-quality medicines. Actavis is an industry leader in research and development, with one of the broadest development pipelines in the pharmaceutical industry and a leading position in the submission of generic product applications globally.
With commercial operations in approximately 100 countries, Actavis 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.
Actavis intends to adopt a new global name – Allergan – pending shareholder approval in 2015.
For more information, visit Actavis’ website at www.actavis.com.
Forward-Looking Statement
Statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Actavis’ current perspective of existing trends and information as of the date of this release. Except as expressly required by law, Actavis disclaims any intent or obligation to update these forward-looking statements. Actual results may differ materially from Actavis’ current expectations depending upon a number of factors affecting Actavis’ 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 Actavis’ products; risks associated with acquisitions, mergers and joint ventures; difficulties or delays in manufacturing; and other risks and uncertainties detailed in Actavis’ periodic public filings with the Securities and Exchange Commission, including but not limited to Actavis’ Annual Report on Form 10-K for the year ended December 31, 2014. Except as expressly required by law, Actavis disclaims any intent or obligation to update these forward-looking statements.
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