Approval of mifepristone (RU 486) in Europe

The discovery of mifepristone (ex-RU486) was the achievement of a large research programme on steroidal compounds with antihormone properties conducted at Roussel Uclaf in partnership with the INSERM unit of Pr. E. E. Baulieu. Mifepristone exhibited a strong affinity to the progesterone and the glucocorticoid receptors. Consequently, it exerted competitive antagonism to these hormones both in in vitro and animal experiments. The identification of the antiprogesterone activity led to propose mifepristone use for the termination of early human pregnancy. Mifepristone at the dose of 600 mg initially used alone, was then used with a subsequent low dose of prostaglandins that led to a success rate of 95% as a medical method for early termination of pregnancy. In parallel, other indications were extended to the cervical dilatation prior to surgical termination of pregnancy in the first trimester, in the therapeutic termination of pregnancy for medical reasons beyond the first trimester, and for labour induction in case of fetal death in utero. The efficacy and safety of that treatment have been confirmed on the basis of more than 10 years of use with close adherence to the approved recommendations. Besides the political and philosophical hurdles that delayed clinical research with this molecule, other potential indications either in gynecological or cancer areas should be further developed.