GAITHERSBURG, MD. — A Food and Drug Administration advisory panel unanimously agreed that the selective progesterone receptor modulator ulipristal acetate is an effective emergency contraceptive with an acceptable safety profile, when used within 5 days of unprotected intercourse or a known or suspected contraceptive failure.
The FDA's Reproductive Health Drugs Advisory Committee voted 11 to 0 that the manufacturer, HRA Pharma, had provided enough information to conclude that the proposed 30-mg dose of micronized ulipristal “reduces the likelihood of pregnancy” when taken as soon as possible within 120 hours after unprotected intercourse or a known or suspected contraceptive failure. The primary mechanism of action of ulipristal, which has a potent affinity for the progesterone receptor, is presumed to be the inhibition or the delay of ovulation, according to the company.
If approved by the FDA, the company plans to market it as a prescription-only product under the trade name “ella.” Ulipristal was approved as an emergency contraceptive in Europe in May 2009 and has been marketed there since October, under the trade name “ellaOne.”
The FDA usually follows the recommendations of its advisory panels.
Currently, the levonorgestrel-based emergency contraceptive marketed as Plan B or Next Choice, is the only available emergency contraceptive in the United States.
Plan B is recommended for use for up to 72 hours within unprotected intercourse or contraceptive failure; it is available by prescription and—for women aged 18 years and older—over the counter, in a 1.5-mg single-dose (Plan B One-Step) and two 0.75-mg doses to be taken 12 hours apart (Plan B or Next Choice).
Ulipristal was evaluated in two phase III prospective, multicenter studies of women aged 18 years and older (in the United States) or aged 16 years and older (in Europe), who received 30 mg of micronized ulipristal within 48-120 hours of unprotected intercourse.
The first trial was an open-label study conducted in the United States of 1,241 women, who were give a dose of ulipristal within 48-120 hours after unprotected intercourse. The pregnancy rate was 2.10%, which was significantly lower than the expected pregnancy rate of 5.53%.
The second study was a randomized, controlled, inferiority study in which ulipristal was compared with levonorgestrel in women in the United States and Europe. Among the 1,694 women who took either medication within 72 hours of unprotected intercourse, the pregnancy rate was 1.78% among those who took ulipristal, which was significantly lower than the expected pregnancy rate of 5.54%. The pregnancy rate among those who received the levonorgestrel emergency contraceptive was 2.59%.
The pregnancy rate was higher among women with a higher body mass index (BMI), in a pooled analysis of the two studies: The pregnancy rate was 3.13% among those with a BMI above 30 kg/m
Among more than 4,700 women in ulipristal studies who received single doses up to 200 mg, including 2,700 women who received the 30-mg proposed dose, the most common side effects reported were headache, nausea, dysmenorrhea, and abdominal pain, according to the company. The one serious adverse event associated with ulipristal was in an 18 year old, who experienced severe dizziness after taking the drug. No ectopic pregnancies were reported; two ruptured ovarian cysts were reported in women who received the 30-mg dose in phase II/III and phase III studies.
The limited data on pregnancies exposed to ulipristal suggest that the miscarriage rate is not increased with exposure, according to the company. Only 21 exposed pregnancies have been reported to date; of those, 14 are ongoing normal pregnancies, 2 were elective terminations, 1 was a miscarriage and 4 were lost to follow-up. The company is planning a postmarketing study in Europe, which will follow up with 1,000 health care practitioners to collect detailed clinical data on the course of pregnancies and outcomes among patients who get pregnant despite treatment with ulipristal. The FDA has proposed that if ulipristal is approved, this program should be expanded to include health care providers in the United States.
Disclosures: Members of FDA advisory panels have been cleared of potential conflicts of interest by the FDA prior to the meeting, but occasionally, the FDA grants a waiver to a panelist with a conflict of interest.