Persistence Brought Abortion Pill to U.S.

The long and tangled journey of the abortion pill to the United States--expected to culminate with its introduction here later this month--began with the zeal of two women, who marshaled a force of moneyed activists to do for themselves what the major pharmaceutical companies would not.

In a highly unusual twist on the way most medications find their way to market, this cobbled-together group took on roles usually reserved for corporate executives and marketing experts, picking its way through the minefields of abortion politics to win federal approval this fall of the drug compound, mifepristone, commonly known as RU-486.

The pill’s 11-year journey to the United States included a cloak-and-dagger scheme to hide the identities of participants from anti-abortion activists; allegations of fraud; a dozen lawsuits; and a price tag of at least $50 million.

The company set up to distribute the drug, Danco Laboratories, has gone through four incarnations and at one point was registered as an offshore enterprise. Citing fear that anti-abortion activists might foment violence against those who make and distribute the drug, Danco refuses to release the names of its executives and investors. The company even persuaded the Food and Drug Administration to keep secret the location of the factory where the abortion drug will be produced, despite several published reports that it will be made in bulk at the state-owned Hua Lian Pharmaceutical Co. in Shanghai.

But the real story goes beyond all that. It is what happens when a group of true believers finds the financial means and the political support to use the private sector to its own ends.

Longtime feminist activists Peg Yorkin and Eleanor Smeal; scientists at the nonprofit Population Council; liberal organizations such as the David and Lucille Packard Foundation; abortion rights activists; and even the president of the United States all played a part.

“What united us, the interested individuals and nonprofits and foundations, was the desire to make this very safe, early option available for women,” said Sarah Clark, who directs the population program for the Packard Foundation. “Abortion is such a toxic subject that the ordinary channels for this drug were not available.”

The existence of the coalition--and its ultimate success on Sept. 28 when the FDA approved mifepristone for use in the United States--has confounded and outraged abortion opponents.

“It’s a whole movement to try to transform the image of abortion,” said Randall K. O’Bannon, director of education and research for the National Right to Life Committee. “To make it from something that’s intimidating and invasive, to make it into just a pill to make the baby go away.”

It was 1989 when Smeal, a former president of the National Organization for Women, and Yorkin, a Hollywood producer with a history of putting her money behind feminist projects, took 700,000 petitions and a team of scientists to France, where mifepristone, then known as RU-486, had been on the market for about a year.

Their goal: to find out whether it really worked and to persuade the compound’s French manufacturer, Roussel Uclaf, to sell it in the United States.

“We had a formidable challenge,” Smeal recalled.

For many feminists, the drug represented an opportunity to make abortion safer, more private and more accessible. It would, to their thinking, disperse the ability to perform abortions throughout the medical community, thwarting anti-abortion activists who often focus their attention on clinics or on publicly identifying doctors who perform abortions.

But the Catholic Church in France had mounted a huge lobbying campaign against the drug, as had anti-abortion forces in the United States. The new corporate owners of Roussel Uclaf, German-based Hoechst AG, wanted nothing to do with the messy, sometimes violent, politics of abortion in America, and in 1988, it even tried to pull RU-486 off the market in France after protests there. But the Ministry of Health forbade it, and now it is used in about a third of French abortions.

“We’re going to have to do it ourselves,” Smeal told Yorkin; then they set about thinking of how that might be done.

Yorkin put up the first big chunk of money--$10 million to the Feminist Majority Foundation, an organization founded two years earlier by herself and Smeal. Much of the money, Yorkin said in an interview, was earmarked for the abortion pill.

“You get to be players at the table if you have the money to do it,” she said. “But it’s taken so long, I was beginning to wonder if it would happen in my lifetime.”

Activists Lobbied in Washington

Along with Katherine Spillar, who runs the Feminist Majority’s West Coast operations and is based in Los Angeles, Smeal and Yorkin launched an information blitz aimed at abortion rights activists, feminists and others who might have an interest in the drug. The group lobbied heavily in Washington, where the FDA, under then-President Bush, had put the pill on a list of medications banned from entering the United States. The group also continued to lobby Roussel Uclaf and Hoechst, which in 1999 became part of giant European drug maker Aventis SA, pleading with executives to cede or sell the rights to the drug in the United States if it did not intend to introduce it here.

Their big break came early in 1993, when newly elected President Clinton, on his third day in office, directed the Department of Health and Human Services to “promote the testing, licensing and manufacturing in the U.S. of mifepristone.”

Soon after, the administration began its own efforts to persuade Roussel Uclaf to either bring the drug to the U.S. or give up its patent rights here.

At one point, Health and Human Services Secretary Donna Shalala intervened personally, phoning company officials and asking them to cooperate.

By the next year, the deal was done. The company gave the patent on mifepristone to the Population Council, a family planning think tank in New York. The organization employs dozens of scientists worldwide to investigate and develop new forms of contraception and had twice been instrumental in finding investors to market controversial products.

“On May 16, 1994, at the request of U.S. authorities, Roussel Uclaf transferred without compensation its U.S. Patent rights on mifepristone [RU-486] to the Population Council, a not-for-profit organization,” reads an entry in Hoechst’s 1994 annual report. “The Population Council has since begun developing the product for use in voluntary termination of pregnancy.”

But then the job got harder.

Clinical trials of the drug had to be conducted in the U.S.--even though it had already been tested and approved in France--to get federal approval for its use here. And once it was approved, someone had to agree to market and manufacture it.

Moreover, the National Right to Life Committee and about 30 supporting organizations started a boycott of Roussel Uclaf and Hoechst for giving the Population Council the patent rights.

“We sent over a delegation to Roussel Uclaf and to Hoechst,” O’Bannon said. “We told them we did not want this pill imported to the United States. And they were told that if they did anything to make it available in the United States, they would be held accountable.”

In the end, Roussel Uclaf and Hoechst gave away their patent rights for France and the rest of Europe. And in the U.S., not a single pharmaceutical company stepped up to the plate to help research, make or manufacture the drug.

The Population Council raised $16 million from like-minded foundations, including the Open Society Institute of New York, which is the philanthropic arm of billionaire George Soros, and the California-based Kaiser Family Foundation.

The money was used to conduct new trials of the drug and to prepare the thousands of pages of documents necessary to win FDA approval. Population Council researchers began clinical trials in October 1994, just five months after Roussel Uclaf ceded the patent.

But more was needed. The council approached Joseph Pike, an investor and lawyer with whom it had worked years before on the development of an intrauterine contraceptive device, and suggested that he put together a group of investors whose money would go toward marketing and manufacturing the abortion pill.

He put in $6 million of his own funds, according to court papers filed in connection with a lawsuit, and approached wealthy abortion rights supporters. One of them was Yorkin, who agreed to invest an additional $250,000 in the distribution company.

By 1996, Pike had raised more than $27 million, according to court documents. Two years later, the Palo Alto-based David and Lucille Packard Foundation kicked in $10 million more in the form of a loan.

“Just think about the money,” said Felicia Stewart, a former Clinton administration family planning official who is now co-director of the Center for Reproductive Health Research and Policy at UC San Francisco. “If it hadn’t been for the willingness of nongovernmental organizations to put monumental money to the task, it wouldn’t have been possible to do it.”

But there were problems.

Pike had set up shop as a nonprofit, calling his organization Advances in Health Technologies. But the company also had two for-profit subsidiaries--Danco Laboratories Ltd. and Neogen Holdings. Another entity, listed in California state documents as Danco Investors Group LP, was registered in the Cayman Islands, where the identities of officers and partners are not required to be disclosed. The general partner for Danco Investors Group, N.D. Management Inc., also is based in the Cayman Islands.

According to documents, the decision to set up the investors’ group as an offshore enterprise came about because participants feared that they would be targeted by abortion opponents, some of whom have assaulted and even killed doctors who had performed abortions.

But even so, the structure was so unusual that one potential investor sent a letter to Pike suggesting that if the deal were to go through, it would be best if “the enterprise would be restructured to be a conventional corporation.”

But before the deal was finalized, the investor, KCC Delaware, discovered that Pike had pleaded guilty to forgery in a real estate deal in North Carolina in the mid-1980s and had been stripped of his license to practice law, according to court documents and an arrest warrant.

KCC Delaware sued, accusing Pike of hiding his past and mishandling the investment deal, which had not gone through. Pike countersued for defamation, naming KCC Delaware along with its executives, who included Hollywood producer turned turnaround specialist Burt Sugarman. He insisted that he had disclosed his history and claimed that the deal had not gone through because of KCC.

In that lawsuit, Pike also revealed something of the nature of his relationships with the Population Council, saying that the organization had the right to veto any investor and had nixed KCC’s involvement in the project.

Meanwhile, however, the word was out about Pike’s past, and by November 1996, the Population Council and its supporters were nervous.

The Population Council sued Pike, alleging that he had failed to disclose his North Carolina record and seeking to wrest control of the company from him.

Pike was forced to step down, and the company, whose name already had been changed once, was reconstituted, first as Neogen and then, after it turned out that another company had that name, as Danco Laboratories.

A new president, Jack Van Hulst, was hired, and a public affairs director was brought aboard.

But the organization’s troubles did not end there.

Van Hulst left in early 1997, though it is not clear exactly when or why.

And in the midst of the FDA approval process in 1997, an unidentified company that had been hired to manufacture the drug backed out.

With a federal deadline for finding a manufacturer looming, Danco moved quickly to sign up another manufacturer, Dutch pharmaceutical company Gedeon Richter.

At the last minute, that company also backed out, according to court papers, and Danco Laboratories was once again mired in litigation.

“On February 28, 1997, Gedeon Richter suddenly notified Danco that Gedeon Richter was terminating the manufacturing agreement,” Danco’s lawyers wrote in a lawsuit against the Dutch firm. The pharmaceutical company also notified the Population Council, according to the documents.

Finally, in 1998, Danco received the $10-million infusion from the Packard Foundation. Months before, the company had hired Roy Karnovsky, a 20-year marketing veteran of pharmaceutical giant Merck & Co., as its new president.

Dr. Richard Hausknecht, an obstetrician at Mt. Sinai Medical Center in New York who specializes in abortion, signed on as medical director.

“I came to it primarily out of conviction,” said Hausknecht, who had been involved in the abortion rights movement for years and had published a paper on a different drug sometimes used to induce abortion. “I had an enormous amount of experience with medical abortion . . . [and] I was at a point in my career where the anti-choice people were less in a position to do damage to my practice.”

Danco’s only other publicly identified employee, public affairs director Heather O’Neill, was fresh out of graduate school at Harvard and had been an intern at the Population Council. She too had joined the organization more out of personal conviction than a search for career advancement.

The little company hunkered down in its unmarked Midtown Manhattan offices, determined to see the rest of the process through.

It hired a manufacturer--reportedly Hua Lian Pharmaceutical Co.--to make the compound in bulk and an undisclosed U.S. company to shape it into pills, although no one at Danco will confirm that and the name has been sealed on FDA documents.

And it developed a marketing plan.

At last, despite cries of foul and accusations of conspiracy from the anti-abortion community, the FDA approved the pill for use in the United States on Sept. 28.

In a strange twist, the FDA acceded to Danco’s request that the name of its manufacturer be kept secret--and even shielded the names of the FDA researchers who had overseen the pill’s approval.

“We looked at the sorts of issues that this product raises and some of the threats and violence that have occurred around the issue of reproductive rights,” an agency spokesman said.

The FDA considered the personal safety of employees at the pharmaceutical plants producing mifepristone, as well as the effect of potentially violent protests on a manufacturer’s business, he said.

“If something were to happen to a manufacturing facility, it could put the company out of business,” he said.

Even FDA Officials’ Names Kept Secret

Even FDA spokesmen--the public relations specialists who field reporters’ calls to the agency--are keeping their names confidential as a condition of being interviewed about the drug.

The Right to Life Committee has concerns about the safety of mifepristone, saying that it can induce heavy bleeding or even hemorrhaging in some women, and raises questions about the secret nature of the U.S. distributor.

“What happens when you try to go back and find somebody who’s accountable and you’ve got all kinds of shell companies and you’ve got a secret manufacturer?” O’Bannon asked.

The FDA has rejected the argument that providing a cloak of secrecy for Danco and its manufacturer will make it difficult for women who might be harmed by the pill’s side effects from seeking a responsible party.

“As it does with all products that it’s considering approving, the FDA inspects the manufacturing facility,” said an FDA spokesman, who like other FDA officials involved with the abortion pill withheld his name.

Once the approval was final, Danco and the rest of the abortion rights community swung into action. The company, which had been so secretive before, suddenly started granting interviews; it hopes to put the pills on the market sometime this month.

The compound will be sold under the name Early Option, with the wholesale name of Mifeprex, said O’Neill, who serves as Danco’s spokeswoman.

It will be marketed not by a phalanx of salesmen, as are most pharmaceuticals, but through brochures sent to doctors and through presentations at medical conferences. With its Web site, which was ready to go when regulatory approval came through, Danco plans to reach out directly to women, she said.

Under FDA rules for the drug, it will not be available in pharmacies but rather through mail-order or other forms of direct marketing by Danco. The pills will be shipped directly to the doctor’s office.

A price has not yet been set, but several sources among those who have worked on the project said the cost has been targeted at around $80 per pill.

To use mifepristone for an abortion, a woman will have to make three visits to the doctor over two weeks.

During the first visit, she takes mifepristone, which acts against the hormone progesterone and prevents the embryo from adhering to the wall of the uterus. Then, two days later, she returns to the doctor’s office and takes another medication, misoprostol, which induces uterine contractions and is meant to ensure that the fetus is expelled. Twelve days later, she sees the doctor to make sure that the pregnancy has ended.

Most of the nation’s top health insurers have said that they will cover the procedure.

Concern over the volatility of the issues surrounding the pill--and fierce opposition on the part of abortion opponents--did not end with FDA approval, however.

The National Right to Life Committee has begun a campaign aimed at highlighting possible negative side effects of using mifepristone to induce miscarriage, which can include dangerously heavy bleeding, powerful cramps or an incomplete abortion.

And Pharmacia Corp.’s Searle unit, which makes the second pill, misoprostol, has attempted to dissociate itself from such use of the medication, which was developed to treat ulcers. Sold under the brand name Cytotec and recently eligible to be made as a generic drug, the medication carries a warning that it should not be taken by pregnant women.

Organizations backing mifepristone have been assigned new tasks as the pill makes its way toward the U.S. market.

The National Abortion Foundation, for example, has been tapped to develop ways to train doctors to administer the pill.

And other groups have taken on additional roles: Stewart at UC San Francisco is working with doctors who have not traditionally performed abortions to see whether some might wish to prescribe mifepristone.

Even the Feminist Majority has taken on a new, somewhat unusual, task. The organization is arranging for men and women with certain types of cancer to get the pill free, because it turns out that mifepristone, which inhibits the hormone progesterone, helps to treat tumors of the brain and other parts of the body.

The mifepristone investors and backers formed “a kind of cobbled-together group of interests to see this product through the marketing process in the United States,” said Michael Nichol, a pharmaceutical economist at USC.

“This is a very unusual way for a pharmaceutical product to come to market,” Nichol said. “The standard channels would have involved a large pharmaceutical company doing all of this.”

It is unlikely that the drug will be a blockbuster in the U.S., despite some published estimates that the market could be as big as $100 million.

In 1996, the most recent year for which there are statistics, American women had 1.2 million abortions. In France, the pill has replaced only about a third of all surgical abortions, probably because it can be used only through the seventh week of pregnancy.

And unlike most drug blockbusters, which are used repeatedly, mifepristone is a drug that most women will take only once, if at all.

“I don’t think anybody thinks they’re going to make a lot of money,” Yorkin said. “We’re just happy that it’s going to be happening.”