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New Morning-After Pill Safe, Effective Panel Says 5 Days After Intercourse
 
 
  MedPage Today
Published: June 17, 2010
 
"women taking the drug five days after intercourse were no less likely to get pregnant than women who took the drug one day after intercourse"
 
GAITHERSBURG, Md. -- An FDA advisory committee voted unanimously that the investigational emergency contraceptive pill ulipristal (ella) is both safe and effective at preventing pregnancy when taken up to five days after unprotected sex or contraception failure.
 
The two 11 to 0 votes of the Advisory Committee for Reproductive Health Drugs -- a panel of outside medical experts amount to a recommendation that the FDA should approve the drug. The FDA does not have to follow the advice of its advisory committees, but it usually does.
 
If approved, ulipristal -- which works by blocking or delaying ovulation -- would be the first selective progesterone receptor modulator (SPRM) available in the U.S for emergency contraception.
 
It also would be the first emergency contraception indicated for use up to 120 hours after unprotected sexual intercourse. Levonorgestrel (Plan B One-Step) must be taken within 72 hours after intercourse.
 
The panel's recommendation for approval was based on data from two phase III clinical trails performed by the manufacturer, HRA Pharma.
 
In the first trial, 1,200 women were given a single dose of either ulipristal or levonorgestrel within 72 hours of unprotected sexual intercourse.
 
There were nine pregnancies among 596 women in the ulipristal group, resulting in an observed pregnancy rate of 1.51%, with a 95% confidence interval from 0.62% to 3.32%.
 
That compared with 17 pregnancies among the 604 women in the levonorgestrel group, resulting in an observed pregnancy rate of 2.81% (with a confidence interval of 95% from 1.54% to 4.97%.)
 
The observed pregnancy rate in each treatment group was significantly lower than the estimated expected pregnancy rate (ulipristal: 5.63%; levonorgestrel: 5.88%).
 
The second study enrolled 1,241 women 18 or older with regular cycles who sought emergency contraception between 48 and 120 hours after unprotected intercourse. The women were treated with a single dose of ulipristal.
 
Pregnancy resulted in 26 of the women for a rate of 2.1%, with a 95% confidence interval from 1.4% to 3.1%, which met both of the study's main objectives.
 
Unlike levonorgestrel, ulipristal remained equally effective over time, so women taking the drug five days after intercourse were no less likely to get pregnant than women who took the drug one day after intercourse.
 
"The efficacy data is convincing," said committee member Melissa Gilliam, MD, MPH, chief of Family Planning at the University of Chicago.
 
Each day, 1 million women who do not want to become pregnant engage in unprotected intercourse, said James Trussell, PhD, director of the Office of Population Research at Princeton. Trussell is an unpaid consultant for HRA Pharma.
 
"Every woman deserves a last chance to prevent pregnancy after unprotected intercourse," Trussell told the panel Thursday morning.
 
Half of all pregnancies in the U.S. are unintended, and four in 10 will end in abortion, Chelsea Bernhardt Polis, PhD, of the Department of Population, Family and Reproductive Health at Johns Hopkins Bloomberg School of Public Health told the panel during a public hearing portion of Thursday's meeting.
 
Emergency contraception is no silver bullet to eliminate unwanted pregnancies, she said, but having another product available will benefit women.
 
Despite the politically contentious issues surrounding emergency contraception, only a few speakers voiced opposition to FDA approval of ulipristal.
 
One speaker, Donna Harrison, MD, president of the American Association of Pro-Life Obstetricians and Gynecologists, said the drug should not be approved because there is insufficient data in the company's trials to conclude what effect, if any, ulipristal has on pregnancy outcomes if a woman becomes pregnant despite taking the drug.
 
In clinical trials and during follow-up surveillance, 110 women have become pregnant despite taking ulipristal within five days from unprotected intercourse.
 
The main cause for the pregnancies was likely having unprotected sex again shortly after taking ulipristal, said Erin Gainer, PhD, MPH, CEO of HRA Pharma.
 
"This is emergency contraception. It's intended to work for the act that occurred a few days before," Gainer said. "If unprotected intercourse occurs again, that's a whole other act," said Gainer.
 
Several members of the public also urged the FDA to avoid adding extra restrictions to prescribing ulipristal, such as requiring pregnancy tests in order to obtain a prescription.
 
"The stipulation is unnecessary because it doesn't apply to other emergency contraceptive products," said Kirsten Moore, president and CEO of Reproductive Health Technologies Project. "We ask the FDA to not once again fall victim to political pressure and subject this product to unnecessary restrictions."
 
The panel agreed with Moore that the labeling should not require doctors to perform a pregnancy test before prescribing ulipristal.
 
"If a woman comes into my office and says she wants emergency contraception, I can pretty much guarantee any physician is going to do a urine pregnancy test to make sure she's not already pregnant," said Valerie Montgomery Rice, MD, dean of the Center for Women's Health Research at Meharry Medical College in Nashville, Tenn.
 
Specifically requiring a pregnancy test is unnecessary, Montgomery Rice said.
 
The committee was concerned with data from the trials that seemed to indicate ulipristal was less effective in women with a body mass index greater than 30. However, data on obese women were lacking -- just 16% of study participants were defined as obese. Panelists were split on whether ulipristal's label should carry a warning that the drug might not be as effective in heavier patients.
 
On the one hand, a number of committee members didn't want to punish the drugmaker for looking specifically at the drug's efficacy in obese women, but others felt women should be told there is a chance the drug won't work as well in obese patients.
 
The most common adverse events in the trials were headache, nausea, dysmenorrhea, abdominal pain, fatigue, and dizziness, which were reported by at least 5% of all women in the studies. The safety profile is similar to that of levonorgestrel.
 
Following years of controversy over levonorgestrel -- which is a popular target of religious conservatives and was the subject of a protracted battle in the FDA under the Bush administration -- the FDA approved Plan B for over-the-counter use in 2006 for women 18 and older. In June of 2009, it approved a one-dose formulation called Plan B One-Step.
 
HRA Pharma applied for approval for ulipristal only as a prescription product.
 
"We currently have no plans to request over-the-counter status for this drug," Gainer said.
 
 
 
 
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