When would a pharmaceutical corporation ever refuse to market an effective, potentially profitable drug? When it is connected to abortion, reports Kathleen Corkey
RU-486: A bitter pill to swallow
Several recent American studies have shown that, in the words of the United States Institute of Medicine, many people's contra-ceptive needs 'remain essentially unmet'. With more women putting off raising families, there is a sizeable gap in the reproductive health market as demand grows for new methods of fertility control. Yet one company involved in these studies, Hoechst Marion Roussel, has dropped just such a drug - RU-486 or mifepristone, the abortion pill.
RU-486 blocks the action of progesterone, the hormone responsible for maintaining pregnancy. This prepares the body for a miscarriage which can then be triggered using another drug, a prostaglandin - taken two days later. It was developed 15 years ago by Professor Etienne Baulieu for the pharmaceutical company Roussel-Uclaf, a subsidiary of Hoechst Marion Roussel. RU-486 is currently used in Britain, Sweden and France to carry out early medical, that is drug-induced, abortions - a safe and effective alternative to abortion done by surgical methods under general or local anaesthetic. The introduction of RU-486 makes late medical abortions significantly less painful and reduces side effects like nausea and vomiting.
Professor Allan Templeton of Aberdeen Hospital outlined some of the advantages to medical abortion for women: 'The largest benefit with RU-486 is that it does avoid the risks associated with anaesthesia and surgery. We have found that avoidance of anaesthetic comes high on the list of preferences for women. Women like to be in control of the situation and not feel as if they have "given up" their body to the surgeon. Also the infection rates are lower due to the lack of surgery, which again some women feel quite strongly about.' Professor Templeton now carries out two thirds of abortions using RU-486, prior to that they were all surgical.
If it were not for the Abortion Act, which specifies that abortion must be carried out in a place registered with the Department of Health, women in Britain seeking an abortion in early pregnancy could obtain RU-486 from a doctor and only attend a clinic or hospital to be treated with prostaglandin. It has even been suggested that women could go through the whole process at home, and simply arrange an examination afterwards with their doctor to make sure there were no retained products. A pill, a check-up at the local GP's surgery, and it would all be over without the need for hospital involvement.
RU-486 or mifepristone has other uses as well. Professor Templeton uses it in the management of miscarriage and for inducing labour. Now studies have shown that a low dose of mifepristone is as effective as the current post-coital contraceptive - the 'morning-after pill' - with fewer side effects. It could also be used to develop a 'once-a-week pill', which would give women the choice of using a pill which does not contain oestrogen or progestogen - the hormones that have traditionally been used and which cause side effects in some women. There is also a possibility of using RU-486 to develop a new form of male contraceptive.
Other potential benefits of mifepristone include possible treatment for endometriosis (a long-term, painful condition involving uterine bleeding), as well as future treatments for Cushing's disease, Multiple Sclerosis and HIV. Studies suggest that mifepristone could be used to treat 40 per cent of breast cancer tumours.
Despite all of this good news, however, mifepristone is being underused, and under-researched. It is only available in Britain, Sweden and France and then only when taken under supervision in hospitals and clinics (it is illegally manufactured and distributed in China). Hoechst Marion Roussel never marketed RU-486 with the enthusiasm or investment normally lavished on a potentially profitable drug. As a consequence, in 1996 the revenue from the product was just $3.4 million. In April 1997 Hoechst Marion Roussel dropped RU-486, and handed the patent rights over to the smaller Excelgyn Laboratoires.
Why did a normally profit-hungry corporation like Hoechst Marion Roussel pass up the opportunity to make a lot of money out of RU-486? The only plausible answer is that its board was afraid of the moral stigma attached to abortion, and put its sensitivities before the interests of patients and shareholders alike.
From the first, Roussel-Uclaf laid down strict criteria for the licensing of RU-486, and these were taken on by Hoechst Marion Roussel. Abortion not only had to be legal in the country concerned, but the right to abortion had to be accepted there by public, political and medical opinion. There had to be a strict medical follow-up of every patient as a part of the clinical protocol; the manufacturers prided themselves on being able to trace every pill produced.
Finally, the company decreed that there had to be a request from the national authorities that RU-486 should be licensed. This was especially sig-nificant. It meant that Roussel-Uclaf itself would not apply for a licence, but would leave it to the government concerned. In countries where abortion was a political issue, the authorities often chose not to license a new drug that might prove contentious. And in countries where abortion was not an issue, governments often chose not to risk starting the debate. The fact that nobody was promoting RU-486 meant that the public were unaware of the new techniques available. As a result, many women were denied the choice of a safe, non-surgical abortion.
When mifepristone was introduced in France in 1989, anti-abortionists made death threats against the staff of Roussel-Uclaf, who immediately stopped distribution and tried to stop production. The French minister of health and social affairs commendably ordered them to restart distribution of the drug, arguing that it was no longer the property of Roussel-Uclaf but was rather 'the moral property of women'. Roussel-Uclaf reinstated RU-486 in France (at that time the only market). However, as the drug was not promoted in any way, doctors were slow to introduce it. Today French medical staff remain reluctant to use this 'new' method, and it is still less well-used than other methods, even in France.
When RU-486 was approved in Britain in 1991 it also sparked anti-abortion protests, and threats to boycott other Hoechst and Roussel-Uclaf products. However, there was no widespread public reaction against RU-486. In fact the influence of those opposed to the abortion pill has consistently been exaggerated. In France, too, despite the threats, the anti-abortion response to RU-486 proved insignificant. Yet it had a disproportionate effect on Roussel-Uclaf, enough to make them end their involvement with the product.
The company stated that it was discontinuing sales of RU-486 because of a 'complete reassesment' of its 'priorities and portfolios'. Behind the corporate speak, regardless of the ineffective boycotts, the company wished to steer clear of a controversial issue like abortion.
The company which now holds the patent for RU-486, Excelgyn is small but determined. Headed by Dr Edouard Sakiz, (president of Roussel-Uclaf at the time of the original RU-486 trials and a 1994 recipient of the US Feminist Majority Foundation's Feminist of the Year), it will concentrate solely on the manufacture, marketing, distribution and development of RU-486.
Excelgyn is committed to research projects into labour induction and post-coital contraception, which were halted by Hoechst. The company also supports increased availability of RU-486. It has plans to request a licence for distribution in other European countries. However, the strict criteria for licensing and distribution used by Hoechst Marion Roussel will still apply. The head of medicine, research and development, Dr Regine Sitruk-Ware, explained that 'due to the controversy surrounding the drug, it needs to be delivered to the patient as safely as possible, in a strictly controlled environment'.
Why is there a need for such tight control of mifepristone? Far more dangerous drugs are subject to far less control. As Dr Sitruk-Ware says, it is all about the political and moral controversy that this drug attracts, not the safety of the drug itself.
After 30 years of legal abortion in Britain, and 22 in France, it is quite startling to find that a small 'pro-life' minority can influence major drug companies and prevent new developments in contraception reaching women. In the UK general election last year, the Pro-Life Alliance won two per cent of the vote. A 1997 Mori opinion poll again showed that only two per cent of the British population disapprove of abortion in all circumstances. Yet this tiny minority manage to retard the availability of RU-486.
Nobody should expect drug companies to make a stand for women's rights. They will only respond to the climate in society, the mood in the marketplace. A campaign by those who want abortion facilities to be expanded to de-stigmatise the procedure could open the way for innovative pharmaceutical solutions to unwanted pregnancies.
Reproduced from LM issue 108, March 1998