Using a set of legal tricks, the pharmaceutical industry was able to turn an animal gallic acid into a medicine that costs tons of money per year. Responsible pharmacist of the Amsterdam Medical Center Marleen Kemper and professor in metabolic diseases Carla Hollak decided in 2018 to start preparing the drug chenodeoxycholic acid (CDCA) for patients with the rare hereditary metabolic disease cerebrotendinous xanthomatosis (CTX) in their own pharmacy in order to circumvent the much more expensive Italian manufacturer Leadiant. Now, the Amsterdam Medical Center produces a new ‘hijacked’ medicine: cholic acid, an affiliated substance of CDCA, which is used in the treatment of gallic acid synthesis defects. This is a scarcely researched orphan drug that lead to a complicated dispute with two American pharmaceutical companies that went on for almost a decade. Only at the end of 2020, the hospital found a new – secret – supplier of the material, after which the research to the beneficial effects could finally begin. The Investigative Desk reconstructs the route towards the manufacturing of the medicine by the pharmacy of the Amsterdam Medical Center itself.
Cholic acid has been won from the bile of slaughtered oxes and sheep for eighty years. In the beginning of the nineties, scientists from France and the United States of America suggested that the acid could benefit a group of patients with congenital metabolic diseases, who have gallic acid synthesis defects. The most severe varieties of these defects are the so-called Zellweger spectrum conditions. The researchers based themselves on the biological argumentation, but real evidence of the beneficial effect of the medicine on the patients was lacking. Nevertheless, two pharmaceutical companies tried to bring the medicines to the European market. Their interest can be explained by new legislation of the American government and the EU, that enabled manufacturers to obtain a monopoly when they found a cure for a rare disease.
The Amsterdam Medical Center contacted the American company Asklepion to order capsules for their research on the Zellweger patients. However, the company failed to deliver the order in time and when the medicines eventually arrived, the legal certifications were not included and the stock was limited. The company claimed to be willing to cooperate and to supply patients with their medicine, but on March 18th 2015, Asklepion sold the complete cholic acid department to Retrophin for 73 million dollars. Retrophin promised to provide the Amsterdam Medical Center with enough medicine for another two years of the study. Nonetheless, the beneficial effect was not yet proven and later on, the company could only provide a limited supply of the medicine. They did offer a research grant, which the hospital declined. The collaboration with Retrophin was discontinued and patients who were possibly benefitting from the medicine were lacking supply. However, a new study on the beneficial effects of cholic acid on the long term has started in October 2020 and the pharmacy of the hospital now produces capsules without interference by Retrophin, who took the product off the European market after disappointing revenues. Where the hospital is getting their supply from after a decade of shortage remains a mystery.
13 September 2021.
The whole article was published in the Dutch national magazine of medicine (in Dutch only).