3. Success stories and hope for repurposing

Some of the most noteworthy successes in drug repurposing haven’t been for rare diseases. The most well-known may be Viagra being used for erectile dysfunction. Created to treat angina, one of its side effects was that it caused erections. In this end, this became the main indication for the drug.

For minorities diseases, there are some drugs that have already been approved. Thalidomide, created to alleviate morning sickness, had to be banned because it caused serious malformations. Nevertheless, now it is used to treat leprosy, an infectious disease that is rare in western countries. And canakinumab, a drug originally used to treat rheumatoid arthritis that was also approved as a therapy for Muckle-Wells syndrome, a rare genetic disease.

Jordi Quintana, director of Business Development at the Barcelona Science Park (PCB) and one of the scientific leaders of this B·Debate, said that even though “repurposed drugs, in general, won’t be a cure,” we have to take into account that “they can alleviate diseases that in many cases are deadly.” In addition to drugs already approved for other uses, there are many classified as off-target. This is a shortcut that allows drugs to be used, without large-scale clinical trials, as long as there aren’t any other alternatives, as is the case with many rare diseases. Others are currently undergoing clinical trials. Following are some examples.

Bruce Bloom discussed the case of sirolimus, a drug used to prevent transplant rejection that can now be used for autoimmune lymphoproliferative syndrome, a very serious and rare congenital disease. Raúl Insa, CEO of a start-up specializing in drug repurposing - SOM Biotech, shared the advances towards using a drug meant for Parkinson to treat a type of amyloidosis, a rare disease that causes proteins to aggregate and damage the nerves and heart. And Noël Raynal, professor at the University of Montreal, explained how they trawl the effects of more than a thousand approved drugs to research new applications. One of them is proscillaridin, a drug to treat arrhythmia that can help low-frequency childhood tumors.

Jordi Mestres, group leader at the Hospital del Mar Medical Research Institute (IMIM), spoke about mechanisms. Drugs may seem selective, but they are far from it. “More than half of all drugs each interact with at least five proteins,” he explained. This promiscuity leads to opportunities as well as dangers. It allows us to expand the drug’s applications, but can also have side effects when the indications and doses are changed.

There are also other ways to focus the work. For example, repurposing not a specific drug but its mechanism of action. If a drug is found to be beneficial but not effective enough, scientists research its mechanism and seek out other molecules that do a better job. This topic was discussed by Marc Martinell, CEO of Mynorix Therapeutics, a company that specializes in research into rare metabolic diseases. One of them, now in clinical trials, is a drug based on one for diabetes, a PPAR gamma receptor agonist, which may be useful in treating adrenoleukodystrophy, a metabolic disease that causes serious damage to the nervous system.

In this joint effort to get drugs to patients, all of the stakeholders seem to play an essential role. Also in the final stage, commercialization. EURORDIS Therapeutic Development Director Virginie Hivert shared her concerns about the fact that repurposing doesn’t necessarily mean more advantageous prices. “It’s a controversial issue,” recognized Quintana and Francesc Palau, director of the Department of Genetic Medicine and the Pediatric Institute for Rare Diseases (IPER) at Hospital Sant Joan de Déu in Barcelona and joint scientific leader of this B·Debate. “Companies reason that, even though it is a repurposed drug and therefore the investment is lower, rare diseases affect fewer patients, which could justify the increase in price.” Although the data and examples vary, and some drugs have hardly changed in price after being repurposed, a study in Belgium observed that, on average, hospitals paid twenty times more for the new use. In some cases, for the same dose and route of administration, the cost was up to 200 times higher.