Mifepristone comes to the pharmacy

The discovery of Mifepristone goes back to the sixties and the sexual revolution when a Dr. Gregory Pincus who is ironically referred to as the father of birth control. His first book The Eggs of Mammals was published in 1936 and his most famous work The Control of Fertility was published in 1965. Collaborating with Dr. John Rock who was a practicing gynecologist and OBGYN their work with hormones would lead to the first successful oral contraceptive pill called Enovid which was licensed in 1960. It was a combination of progesterone and estrogen that would change the world for better or worse.

Not long after in France Roussel Uclaf a Pharmaceutical company found while experimenting with the synthetic hormone norethindrone that placing a 4-dimethyl-amino-phenyl group at a particular position resulted in the greatest affinity for the progesterone receptor without activating it. That compound which the company coded as RU38486 is now known as mifepristone. It has been in the news recently as the FDA has updated their REMS (Risk Evaluation & Mitigation Strategies) guidance to allow pharmacies to dispense it pursuant to a prescription. CVS and Walgreens, never missing an opportunity to pile a little more on their staff's plate, have already announced their intentions to carry the product.

As a progesterone blocker administering the drug during pregnancy will cause the endometrium to break down. Proper functioning of the endometrium is a necessity for the pregnancy to continue and when it is disrupted by a progesterone blockade the environment will no longer be conducive to the embryo's existence. To further assist in full expulsion the prostaglandin misoprostol is also administered which stimulates uterine contractions. Given in combination this has become the treatment of choice when removal of the embryo is necessary. It has also been shown to be safer and more cost effective compared to suction alternatives. The drug has several other uses including endometriosis, Cushing's syndrome, breast cancer, uterine fibroids and it can even be used to induce labor but none of those uses would come to define it.

Trials with the new compound would start in the eighties and by 1988 it would be approved for sale in France with a one week waiting period. One source boasted that it was used by 100 French women a day. Internationally it was not as well received and was causing serious headaches with Russel Uclaf’s parent company Hoechst. They were concerned about political blowback and a boycott by the American public. Apparently not without actual merit because several years later, they would give the drugs patent away to appease anti-abortion groups who were refusing to use their new allergy medication Allegra. Hoechst executives in private would admit that the pro-life argument that they were doing to fetuses what the Nazi’s did to the Jews hit a little close to home. Hoechst parent company IG Farber supplied the cyanide gas used by the concentration camps and would throw much of its political weight behind a young Adolf Hitler.

Importing Mifepristone to the United States was illegal and customs would go digging through your bags to confiscate it at the airport. One California woman would be caught this way and appealed her case all the way to the supreme court despite being ultimately unsuccessful. The political winds would begin to change in America with the election of Bill Clinton who would order the FDA to investigate the drug's use for abortion. By 1995 Russel Uclaf would give the American patent rights for the medication to The Population Council, an international NGO. The Population Council's goal is to help achieve a "humane, equitable, and sustainable balance between people and resources".

If you're wondering why a drug patent would be given to an NGO and not a drug company, well here lies the heart of mifepristone's problems. It was not very profitable, and no company wanted to touch it out of the very real fear of boycotts. Finding a company to manufacture and distribute it was going to require some extraordinary measures and deep pockets. Fortunately for NGOs like The Population Council the Buffett Foundation and Rockefeller Brothers Fund are big donors. That makes it a little easier to fly down to the Cayman Islands to incorporate a drug company and thus Danco Laboratories was born. Danco does not exist to make money, it exists to distribute mifepristone. That is taking the culture war bull by the horns right there. Ironically mifepristone would become a lucrative drug when another company would use a slightly higher dose to treat Cushing's syndrome and market it under the name Korlym which at 550 dollars a pill cost 180,000 annually per patient.

Roussel Uclaf has an interesting history, it was founded in 1920 by a Dr. Gaston Roussel who would make the company an international success expanding its operations into Mexico, Brazil, and Argentina. Upon his death in 1947 his son Jean-Claude would assume control of the company. If there was an equivalent to the American dream for France this is probably it, the young Jean-Claude was a successful industrialist and pharmacist. The company would continue to grow and thrive, it was said to be a source of great pride for the French people. In 1968 Jean-Claude finds himself on a vacation in the south of France where he meets with a director of Hoechst, a German chemical company. I don’t know what was discussed between the two men and perhaps that is a mystery left to history, but the result was Hoechst purchasing 43% of Roussel Uclaf and Jean-Claude had a newfound desire to “Europeanize” his company.

This was unheard of at the time, and it did not sit well with the French government who considered foreign ownership of their pharmaceutical industry a bad idea. Jean-Claude would have to make many promises to get the deal to go through. He had to agree to never sell any of his own shares and guarantee that no foreign company would ever completely take over the industry. The French government was also given control over the future sale of stock in the company.

Despite those plans an unfortunate accident would throw the company in disarray, setting the stage for a corporate takeover. Jean-Claude was flying his own helicopter to his summer home when he ran into a cable causing him to crash, killing everyone on board. Jean-Claude was a decorated pilot with over 20 years of experience flying his own helicopters. The circumstances around his death certainly raise eyebrows if nothing else. Settling his estate would prove to be a financial mess and his interest in the company would have to be sold. The French government which was already toying with the notion of nationalizing the industry would panic and attempt to convince other large French companies Rhone-Poulenc and Elf-Aquitaine to step in and buy it. They would both decline and the French government itself would wind up buying 33% while Hoechst managed to increase its holdings to 51%.

Jacob Hyatt Pharm D.
Father of three, Husband, Pharmacist, Realtor, Landlord, Independent Health and Medicine Reporter
www.pharmacoconuts.com

www.glenallenliving.com

@Hyattjn

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