Prepared Remarks of Dr. Donna Harrison President, American Association of Pro Life Obstetricians & Gynecologists Presented to FDA’s Advisory Committee for Reproductive Health Drugs Regarding Ulipristal Acetate (“ulipristal”) Tablets (NDA 22-474) June 17, 2010 Good Afternoon. I am Dr. Donna Harrison, board-certified OBGYN. On behalf of the American Association of Pro-Life Obstetricians and Gynecologists I want to thank you for allowing us to address this committee. Our concerns regarding the lack of safety studies for ulipristal are detailed in our written submission in your folder. I will limit comments to the lack of reproductive toxicology information, without which ulipristal should not be approved for use in women of childbearing potential. The European Medicines Agency noted that, “As expected, ulipristal acetate is embryotoxic at low doses.” The EMEA also noted, “Ulipristal acetate prevents progesterone from occupying its receptor, thus the gene transcription normally turned on by progesterone is blocked, and the proteins necessary to begin and maintain pregnancy are not synthesized.” Ulipristal’s embryolethal and fetocidal action is identical to mifepristone, from which ulipristal is derived. Both act at the level of the ovary-inhibiting granulosa cell production of progesterone needed to maintain pregnancy through the first 10 weeks of gestation. Both also directly block progesterone receptors at endometrial glands and stroma, destroying maternal placental tissues. Information on this embryotoxic and fetotoxic mechanism of action is critical to informed consent for women. Many women have ethical qualms about using a drug capable of aborting an early pregnancy. Clear information about the embryotoxic and fetotoxic potential must be included on the product label for adequate informed consent. It is predictable that progesterone blockade will have profound embryolethal and developmental effects on the embryo fetus exposed to ulipristal. Yet, reproductive toxicology studies were never completed. The effect of ulipristal on fetal development is unknown, highlighting the failure of the European voluntary pregnancy registry to provide answers to this critically important question, and illustrating the need for a mandatory fetal registry such as the one now utilized for accutane. Since fetal safety information is lacking, the EMEA label states “Ella One is contraindicated during an existing or suspected pregnancy.” However, in use as an emergency contraceptive, it is impossible to prevent ulipristal use in pregnancy, as illustrated by the clinical trials which support this NDA. In each trial, there were women whose urine pregnancy tests were negative prior to use of ulipristal, but were later found by pre-administration serum pregnancy tests to have been already pregnant at the time of ulipristal use, so under the best circumstances of a clinical trial, pre-existing pregnancy could not be excluded. The European Medicines Agency noted that ulipristal can be detected in reproductive tissues up to 14 days after administration. In the real world, it is inevitable that women who are already pregnant will unknowingly take ulipristal. In addition, ulipristal’s 2% failure rate means that 2 out of every 100 women who use this drug will carry a fetus exposed to ulipristal, a drug known to interfere with placental development. It is irresponsible that basic reproductive toxicology studies called for by the ICH GCP Guidelines, for drugs designed for use in women of childbearing potential, have not been completed for ulipristal. Voluntary fetal registration from Europe has proven to be inadequate to answer basic questions of safety. Since use of ulipristal as emergency contraception will inevitably result in women using the drug in pregnancy, approval of ulipristal will put the FDA in the untenable position of approving a drug which is contraindicated in pregnancy for an indication in which use in pregnancy is inevitable, and for which inadequate safety information is available. This reason alone is sufficient for the FDA to deny approval of ulipristal for use as emergency contraception. Our other concerns are detailed in our written submission. Thank you.