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FDA panel recommends approval of new emergency contraceptive pill
Ulipristal acetate pill already available in 22 European countries
American women might have another option in emergency contraception (EC) if the Food and Drug Administration (FDA) follows the recommendation of its reproductive health panel in approving ulipristal acetate (UPA). Members of the FDA's Advisory Committee for Reproductive Health Drugs voted 11 to 0 during a June 2010 meeting that the material presented by prospective manufacturer HRA Pharma of Paris, France, indicates the drug is effective and safe for use as an emergency contraceptive.
The drug, marketed overseas as ellaOne, was approved in May 2009 by the European Commission for use as an emergency contraceptive within 120 hours of unprotected sexual intercourse or contraceptive failure. Launched overseas in October 2009, the drug is now marketed in 22 European countries. If approved, the drug will be sold in the United States as ella by Watson Pharmaceuticals of Corona, CA. Watson entered into a licensing agreement with HRA Pharma to market the prospective emergency contraceptive.
If approved, ella would represent the first selective progesterone receptor modulator available in the United States for the indication of EC. It also would be the first EC drug product indicated for use up to 120 hours after unprotected intercourse. Both Plan B One-Step (Teva Women's Health, Woodcliff Lake, NJ) and Next Choice (Watson Pharmaceuticals) are indicated to be taken as soon as possible within 72 hours after unprotected intercourse.
While the committee's vote might be considered by the federal agency, the FDA is not bound to follow its recommendation. Family planning advocates may recall that in December 2003, a similar advisory committee recommended approval to move the emergency contraceptive Plan B to over-the-counter status. Final agency approval did not come forth until August 2006. HRA Pharma is not requesting non-prescription access to ella.
There are about 3 million unintended pregnancies each year in the United States, states Kirsten Moore, and chief executive officer of the Reproductive Health Technologies Project, a Washington, DC-based advocacy organization. Despite the many highly effective birth control options women now have to choose from, none are 100% perfect, she notes. "Sometimes, a woman needs a backup birth control method. A condom breaks. A diaphragm slips. A woman forgets to take her pill," states Moore. "There also are cases when sex is unplanned or, unfortunately, unwanted. Every woman's circumstances are different. Ella gives a woman another emergency contraceptive option to prevent unintended pregnancy."
Data indicates efficacy
The 2010 committee's vote followed a review of data from the ulipristal acetate preclinical and clinical development program. The data included the experiences of more than 4,000 women from the United States and Europe, representing the largest development program ever conducted in the emergency contraceptive field, according to HRA Pharma.
In a statement following the committee's vote, Vanessa Cullins, MD, vice president for medical affairs at the New York City-based Planned Parenthood Federation of America (PPFA), said, "Ella, or UPA, is safe and effective at preventing ovulation and, therefore, pregnancy in the five days after unprotected intercourse. Given the fact that half of all pregnancies in the U.S. are unintended, it is vital that women have an array of choices available to prevent unplanned pregnancy."1
The committee reviewed data from two Phase 3 trials. One investigation was an open-label trial conducted in the United States. Its primary objective was to evaluate the efficacy of a single 30 mg dose of ulipristal for EC when used between 48 to 120 hours after unprotected intercourse.2 The other study was a randomized, single-blind trial conducted in the United States and Europe. Its primary objective evaluated the efficacy of a single 30 mg dose of ulipristal for EC, taken 0-72 hours after unprotected intercourse, compared to that of a single dose of 1.5 mg of levonorgestrel.3
Findings from both studies demonstrate that treatment with ulipristal acetate administered within 120 hours after unprotected intercourse is effective. Adverse events reported by at least 5% of women in the two clinical trials were headache, nausea, dysmenorrhea, abdominal pain, fatigue, and dizziness, similar to those experienced by women who use levonorgestrel EC.
How does it work?
According to background documentation filed by HRA Pharma prior to the FDA committee meeting, ulipristal acetate appears to inhibit or delay ovulation, depending on the time of administration in the follicular phase. Administration of ulipristal in the luteal phase also alters the endometrium.4
"Based on the findings of the pharmacodynamic studies, ulipristal appears to exert an anti-progesterone contraceptive effect on both the ovary and endometrium, depending on the dose and time of drug administration during the menstrual cycle," the documentation states. "The Summary of Product Characteristics (the basis for European labeling) currently states that 'the primary mechanism of action is thought to be inhibition or delay of ovulation, but alterations to the endometrium may also contribute to the efficacy of the product.'"4
It is important to point out that ulipristal acetate suppresses LH (luteinizing hormone) surge after it starts, whereas levonorgestrel emergency contraception works up to point of LH rise, says Anita Nelson, MD, professor in the Obstetrics and Gynecology Department at the David Geffen School of Medicine at the University of California in Los Angeles.
Advocates seek approval
The vote by the FDA advisory committee that ella is safe and effective as a form of emergency contraception is a common sense recommendation made by scientific experts, said Cecile Richards, PPFA president of Planned Parenthood Federation of America.
"There are many reasons why a woman may face the risk of unintended pregnancy from failure or improper use of birth control, to sexual assault and every woman deserves every option available to prevent an unplanned pregnancy," Richards stated.
PPFA, along with 19 other reproductive health groups, have submitted a letter to the committee urging approval of the drug. By having two types of safe and effective emergency contraception, the likelihood would increase that a woman can access a product that works for her situation.
Ella meets the FDA standards for drug approval, said Moore in comments before the FDA committee.5 "We ask the FDA not to fall victim once again to political pressure and subject this safe, effective product to unnecessary restrictions that may limit a woman's access to a time-sensitive method of backup birth control," said Moore.
Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta, says he is not particularly excited about this new emergency contraceptive pill, even though it is somewhat more effective. The reason? Emergency IUD insertions (E-IUDs) are more effective as emergency contraception and might provide long-term pregnancy protection, Hatcher states. In one study, more than 80% of women receiving a copper IUD for EC continued use of the IUD as their ongoing contraceptive.6