|In a previous episode this blog has been reporting on a Dutch dispensing chemist who took it on himself the affordable production of a certain drug, otherwise only available from the pharmaceutical industry at highly inflated prices. This week in the news (link) a hospital doing something similar. This time the expensive drug is chenodeoxycholic acid (CDCA), the manufacturer is Leadiant, the disease is cerebrotendineous xanthomatosis (CTX) and the hospital the Academic Medical Center (AMC) in The Netherlands. |
Forty years ago this drug just costed around 500 euro but recently the price has sky-rocketed to 200,000 euro per patient per year. The number of patients in this country is very small (50 and hence CDCA is an orphan drug), the disease causes excessive production of cholesterol in the body and CDCA is a natural bile acid able to dissolve this excess (It also used to be an effective treatment for gallstones). The hospital claims it will bring down the price of CDCA to just 20,000 euro per year per patient but the article is unclear about just how production will take place. Not a problem of course but we are just curious.
This website explains an average treatment requires three 250 mg pills a day per year. The total annual requirement is then 273 grams. Wikipedia explains the compound was first isolated from domestic goose (that explains the latin cheno prefix) but it is unlikely the hospital has taken this road (goose farming) as the start of a production line. A 1972 patent describes an organic synthesis from cholic acid in several steps (link) , basically removing the unwanted alcohol group from the steroid skeleton via the hydrazone and a Wolff-Kishner reduction. Cholic acid is industrially sourced from bovine bile. Other candidates are unlikely. There is the inevitable total synthesis route first explored in 1981 (doi) starting from an oil-based precursor (source). In ursodeoxycholic acid geese are replaced by bears (Ursos produce a different bile acid). This compound is an epimer but plenty of literature exists on cheno to urso conversion but not the other way round. Bear bile is much sought after in Chinese fake medicine (also known as traditional medicine) having given rise to the despicable bile bear industry.
Any other candidates? Interestingly, chemicals supplier Sigma Aldrich sells the compound for (97% pure) for just 416 euro per 25 grams (link), that would make a full treatment cost just 4500 euro. The only thing the AMC footage revealed was a worker filling up capsules, not exactly an organic chemistry laboratory. A repackaging scheme like this is plausible and would generate a profit of 15,000 euro.