LYON, France – Confronted with a young male transplant patient who could only be saved with fumagillin, an antiparasitic drug that is no longer produced, multiple teams from Lyon Civilian Hospitals (HCL) set out to redo the treatment.
Fabrice Pirot, PhD, PharmD, pharmacist and head of Fripharm, the pharmaceutical production, research and innovation platform of hospitals and universities of the pharmacy of the Édouard-Herriot Hospital in Lyon, explained the treatment to Medscape medical news. “Fumagilline is a past treatment that secures a future for our patients.” Thanks to an exceptional wave of support, Fripharm was able to recreate the drug and save 28 patients across France.
In 2020, Noémie Laverdure, MD, PhD, a physician in the pediatric hepatology, gastroenterology and nutrition department at Lyon Maternity Hospital, was confronted with repeated transit problems in a 15-year-old liver transplant patient named Raphaël. Tests conducted by Meja Rabodonirina, MD, PhD, a biologist specializing in parasitology, revealed that the patient was infected with a fungus from the microsporidia family: Enterocytozoon bieneusia. This fungus causes severe diarrhea that can be life-threatening in immunocompromised patients such as Raphaël. The only possible treatment to cure it is fumagillin, an antiparasitic agent that has been used since the 1950s.
Stocks were exhausted
The problem was that production of this drug had stopped in 2019 and the last stocks of HCL’s fumagillin had been used up by March 2020. A support network consisting of multiple HCL departments, the French National Reference Center for Microsporidiosis at the University of Clermont-Ferrand Hospital and the Fripharm Pharmacists was established. They were asked to find raw material to manufacture this treatment again.
“We’ve reached out to suppliers in India, China and Europe,” Camille Merienne, PharmD, PhD, pharmacist in charge of the Fripharm control lab, told Medscape. “We’ve scoured the world to find a stock of active material!” Finally, the team learned that a 300g stock of raw material was available for destruction in Hungary. “We were able to identify a production site that had this last remaining amount. They agreed to supply us with the raw material. We couldn’t have done anything without their help.”
Custom Medicine
Because the active ingredient molecule is extremely sensitive to light and heat, it was kept at -80°C (–112°F) during transport. With this raw material, the pharmacists of Fripharm produced a tailor-made medicine in the form of an oral suspension. “We had three patients in Lyon who were in critical condition. One of them died while we were looking for the raw material. As for the other two, the parasite disappeared from their stool after 15 days of treatment. Their intestinal mucosa recovered after a month , and their intestinal transit returned to normal after 3 months,” Pirot said.
The news then spread and other patients in Lyon, Grenoble, Clermont-Ferrand, Paris, Bordeaux, Rennes and Nantes were able to be treated thanks to the fumagillin produced by Fripharm. “Over the course of 18 months, we were able to treat 28 patients,” says Pirot.
Guarantee continued production
But the 300g of active ingredient recovered in Hungary won’t last forever, and the platform’s pharmacists are concerned to ensure that production continues. “The next steps are to partner with an active ingredient manufacturer. Once we achieve this, we can prepare the drug,” Pirot told Medscape. Two chemistry labs have already expressed interest. “We are currently doing feasibility tests. Then we have to calculate the costs and then find the financing. Once we have the raw material, we can manufacture the drug again in France and even offer it to other European pharmacies.”
“The fumagillin that we have been able to recreate in HCL is critical. Without this cure, immunocompromised patients, including all transplant patients infected with microsporidia, have almost no chance of survival. We have to find solutions either way, or the now with the public is authorities or in the private sector. It is unthinkable not to save patients if we know how to do it,” Rabodonirina said in a press release.
This article has been translated from the Medscape French edition.
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