“The Blue Sheet” Vol. 36, no. 17

April 28, 1993

"The Blue Shoot"

- 9 -
RU 486 WILL BE MANUFACTURED BY U.S. COMPANY;
POPULATION COUNCIL TO CONDUCT CUNICAL TRIALS
Roussel-Uclaf and the New York City-based Population Council announced a licensing agreement April
20 in which the research group will conduct large-scale
clinical trials of the abortifacient RU 486 (mifepristone)
in the U.S. as a prerequisite to FDA approval of the
drug and a prostaglandin as an alternative to surgical
abortion. Under the agreement, RU 486 will be manufactured by a U.S. company for use in the U.S.
The Population Council is establishing criteria for
the selection of a U.S. firm to manufacture the product
upon FDA approval. Roussel-Uclaf will supply the
abortifacient for the clinical trials, which will include at
least 2,000 patients.
Roussel-Uclaf President Edouard Sakiz, Population
Council President Margaret Catley-Carlson, FDA Commissioner David Kessler and other interested parties met
at the agency's headquarters on April 20 to discuss the
basic elements of the agreement and what data would be
required from the trials and from Rbussel-Uclaf.
The groups agreed on 2,000 patients as a minimum
number. FDA will also require efficacy data from the
trial, although the agency noted that efficacy information
from French trials will help toward that requirement.
Roussel reported recently that it has been contacted
by 10 U.S. firms about manufacturing the drug in the
U.S.
Adeza Biomedical, Cabot Medical and Gynex all
have written to Rep. Wyden (D-Ore.) expressing interest
in licensing the drug. Cabot said it is still willing to
manufacture the compound and will "probably" contact
the council. Gynex also intends to contact the organization. Adeza said it is no longer interested in licensing
the drug. Groups that have expressed interest to
Roussel-Uclaf include small- to medium-sized companies, as well as a few venture capital groups, the firm
said.
The U.S. trials will collect efficacy data as well as
data to help determine what type of distribution might
be appropriate for RU 486 in the U.S. Trials may
include administration of the drug in different settings,
such as in existing women's health clinics, or by physicians not currently performing abortions, the Population
Council said. It "may be a necessity" for the organization to find an outside firm to assist with the trials,
the council remarked.
Roussel-Uclaf has agreed to submit European data,
including toxicology, pharmacology, chemistry, safety
and efficacy data, to FDA. The firm said it must first

reformat the data to FDA's specifications. Strict control
of distribution has been one of the firm's basic requirements for introducing the drug into a new market.
The Population Council is expanding its RU 486
advisory body to include groups such as women's health
advocates and physicians. The group will help determine
the details of the clinical trial or trials to be conducted
by the council. The Menlo Park, Calif.-based Henry
Kaiser Family Foundation has agreed to help the council
with the starting costs and to help raise funds for the
trials. The council's goal is to raise at least $4 mil. in
private funding.
Searle May Not Allow Testing Of Cytotec With RU 486
The council previously conducted Phase II clinical
trials of RU 486 as an abortifacient at the University of
Southern California and at clinics outside the U.S. The
organization plans to amend its existing IND (investigational new drug application), filed in 1982 and
amended in 1984, to cover the planned trials.
In the earlier U.S. trials, confirmed by tests in *
France begun in 1981, RU 486 showed a 65%-80%
effectiveness rate for pregnancy termination. The nonprofit group halted its study of RU 486 in 1990 when
Roussel cut off supplies of the drug. Later testing in
France showed that RU 486 followed by a prostaglandin
yields a 96% effectiveness rate ("The Blue Sheet," Mar.
24, p. 6).
RU 486 has been used by over 100,000 women in
Europe, and the drug is currently available in France,
Great Britain and Sweden. The antiprogestin is administered orally in three tablets of 200 mg each, followed
36-48 hours later by a prostaglandin.
The prostaglandin used with RU 486 in Europe is
Searle's misoprostol (Cytotec). In France, the Ministry
of Health directed Searle to change the labeling of the
drug, which is contraindicated in pregnancy, to allow for
its administration to pregnant women in specialized
hospitals.
Searle has tried to distance itself from any connection to abortion, emphasizing that the company has not
and does not plan to conduct trials of Cytotec as an aid
to abortion. Cytotec is indicated for the prevention of
NSAID-induced ulcers.
Upjohn also markets a prostaglandin, dinoprostone,
in a vaginal suppository dosage - Prostin E2. Upjohn's
drug is already indicated for the termination of pregnancy. Oral or intravaginal products are seen as preferable
to intravenous prostaglandin because of cardiovascular
side effects associated with the I.V. form.

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