Searle Cytotec Abortion Use Clears FDA - In Another Sponsor's Label

Pharmacia faces a delicate challenge in managing the political fallout from the FDA approval of the abortifacient Mifeprex (RU-486).

Mifeprex (mifepristone) will be marketed by Danco Labs under license from The Population Council. The medical procedure, however, relies on administration of Pharmacia/Searle's Cytotec (misoprostol).

Searle has worked to distance itself from the RU-486 debate over the past decade. As the deadline for action on Mifeprex neared in August, Searle issued a "Dear Health Care Provider" letter emphasizing that Cytotec is contraindicated for use in pregnant women and not approved for induction of labor or abortion.

Mifeprex labeling, however, states in the indication section that "patients taking Mifeprex must take 400 mcg of misoprostol two days after taking mifepristone unless a complete abortion has already been confirmed before that time." Mifepristone "sensitizes the myometrium to the contraction-inducing activity of prostaglandins," labeling states.

In France, where mifepristone has been available since 1989, the Ministry of Health directed Searle to change Cytotec labeling. However, given the August labeling change to strengthen the warning against use in pregnancy, Searle is unlikely to adjust Cytotec labeling to conform with Mifeprex.

Regardless of the labeling of Cytotec, Pharmacia is likely to face criticism from abortion opponents who will view it as profiting from the new procedure.

Cytotec sales in 1999 were approximately $120 mil., and the product was not a significant consideration in Pharmacia's acquisition of Monsanto in 2000. The use of Cytotec as an abortifacient will not add significantly to Pharmacia's revenues, since the product is priced for chronic use. The two-tablet dose indicated in Mifeprex labeling lists for less than $2 AWP.

The approval of Mifeprex brings a second pharmaceutical issue into the Presidential campaigns. For most brand name companies, a change of topic from the cost of drugs to seniors will be welcome.

The Sept. 28 approval came two days ahead of the well-publicized FDA user fee deadline for the application, allowing the agency to affirm that political motivations played no role in the approval.

However, the approval of RU-486 has been closely coordinated by FDA and the Clinton Administration since the transition process following the 1992 Presidential elections.

Former FDA Commissioner David Kessler publicly committed FDA to the position that an indication for medical abortion would be approvable during the last months of the Bush Administration. He worked with the Clinton Administration to encourage Hoechst to surrender patent rights to RU-486 in the U.S. Kessler is now dean of Yale Medical School and an advisor to Vice President Gore's Presidential campaign.

The Sept. 30 review deadline was six months after the sponsors filed a response to the most recent FDA "approvable" letter for the product.

The timing of the deadline was acute: by ensuring completion of the review within fiscal 2000, FDA was prepared for a potential appropriations rider that would deny funding for the review in fiscal 2001. Rep. Coburn (R-Okla.) tried unsuccessfully to attach such a rider to the agriculture appropriations bill this year.

With RU-486 now approved, the focus of legislative activity will switch to restricting use of the product. Coburn said Sept. 28 that he plans to introduce a bill that would overrule FDA's decision to allow physicians not trained in surgical abortion to prescribe the drug (¹ (Also see "Mifeprex Label Allows Use By Physicians Not Trained In Surgical Abortion" - Pink Sheet, 2 Oct, 2000.)).

From a presidential campaign point of view, the Sept. 28 approval will make RU-486 germane for discussion during the national debates. Danco's projection for a late October launch would suggest another round of publicity just before election day.

For FDA, the political risk from the approval depends on the outcome of Congressional elections. If the agency's oversight or appropriations committees are chaired by abortion opponents, FDA could face a difficult climate heading into the re-authorization cycle for the Prescription Drug User Fee Act.

The agency's release of information about Mifeprex represents sensitivity towards the possibility that individuals involved in the review could face retaliation. All the review materials released by the agency are anonymous, with individual reviewers' names redacted. FDA also redacted the signature and the name of the recipient from the approval letter.