On June 18, 2010, the US Food and Drug Administration (FDA)'s Reproductive Health Drugs Advisory Committee voted unanimously in favor of approving the new drug application (NDA) for ulipristal acetate tablets, 30 mg (ellaOne; Laboratoire HRA Pharma), for use as an emergency contraceptive.

The 11-member committee voted unanimously that sufficient information was available about the efficacy of ulipristal. They also agreed that the safety profile appeared to be acceptable for the proposed indication.

The committee's vote was based on a review of data from the ulipristal acetate preclinical and clinical development program including more than 4000 women from the United States and Europe. The panel agreed that there is no scientific evidence that at the dose recommended, ulipristal causes abortion

BACKGROUND

On October 15, 2009, the US Food and Drug Administration (FDA),s received a request for approval for ulipristal acetate, a selective progesterone receptor modulator, as an emergency contraceptive indicated for the prevention of pregnancy following unprotected intercourse or a known or suspected contraceptive failure.

The proposed dosing regimen is one 30-mg tablet taken orally as soon as possible within 120 hours (5 days) after unprotected intercourse or a known or suspected contraceptive failure. As a method of emergency contraception (EC), ulipristal acetate is not intended for routine use as a contraceptive.

Progesterone plays a pivotal role in reproduction in many species. It is involved in the control of ovulation, implantation, and maintenance of pregnancy. Progesterone mediates its physiological effects through interaction with the progesterone receptor, a member of the superfamily of nuclear receptors.

The recognition of the important role of progesterone in reproduction led to the development of synthetic progesterone receptor ligands, also known as selective progesterone receptor modulators.

Also known as CDB-2914, ulipristal acetate was originally synthesized by Research Triangle Institute (RTI) under contract with the National Institute of Child Health and Human Development (NICHD). NICHD carried out the initial preclinical and clinical development of the compound until HRA Pharma licensed-in the molecule in 2000 and took over its development.

Ulipristal acetate (17α-Acetoxy-11β-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione) is a derivative of 19-norprogesterone that binds with high affinity to the progesterone receptor. A new molecular entity, it is the first member of a new pharmacological class of selective progesterone receptor modulators (SPRMs) designated by the “pristal” suffix.

Ulipristal acetate was approved in May 2009 by the European Commission for marketing as an emergency contraceptive within 120 hours (5 days) of unprotected sexual intercourse or contraceptive failure. The product was launched in October 2009 and is marketed today in 22 countries in Europe.

With the information obtained in clinical studies including four efficacy trials in which over 4,000 women at risk of pregnancy from unprotected sexual intercourse or failure of a contraceptive method received ulipristal acetate for EC, it is concluded that:

• ulipristal acetate reduces pregnancy risk when used up to 120 h after intercourse
• ulipristal acetate has a well-characterized safety profile, with the most frequently reported adverse events (headache, nausea, dysmenorrhea and abdominal pain) being those commonly reported in studies of EC and similar to those described for approved products
• ulipristal acetate would offer women and healthcare professionals an important new treatment option for reducing the risk of unintended pregnancy