If Zantrene® is so good, why was it lost?This actually happens...

If Zantrene® is so good, why was it lost?

This actually happens more often than you might expect. Studies have shown that roughly a quarter of drugs discontinued after a Phase III trial are deprioritized for strategic reasons. In the case of Zantrene, there were a number of factors that brought about its premature demise.

In the late 80s, Zantrene’s original path through the clinic culminated in a long Phase III breast cancer trial funded by the drug’s developer, Lederle Laboratories. During this trial the investigators discovered that Zantrene was being administered incorrectly and were forced to increase the dosage. This mid-trial alteration irretrievably compromised the trial and prevented it from being used to register Zantrene with the FDA in the US. With Lederle’s parent company, American Cyanamid, going through significant legal and financial strife in the 90s, it was never going to fund a new Phase III trial. This essential killed any hope Zantrene had for use in the US.

It did, however, gain approval in France and was marketed there for a short time. Then in 1994, as part of American Cyanamid’s attempt to stay afloat, Lederle Labs was sold to American Home Products, who had little interest in oncology. Investment records from that time also show that Zantrene was not on the list of assets in the Lederle portfolio. In 2002 AHP changed its name to Wyeth, and eventually was sold to Pfizer. By that time the patents protecting Zantrene had expired and it had become a generic drug, effectively owned by no-one.

In addition to the failed trial and portfolio confusion, the market for AML in the 1990s was not as profitable as it is today. Drugs were cheaper and there were few incentives to develop anti-cancer agents for rare indications like AML. Zantrene was never going to generate a great deal of profit in the 90s so be it intentionally, or unintentionally - it was eventually lost.

Now all this can explain why Zantrene was overlooked in the past, but it’s also important to acknowledge the present. As of today, the primary application for Zantrene is as an inhibitor of FTO. This incredible property of Zantrene wasn’t discovered until 2020. Similarly, its cardio-protective abilities weren’t discovered until 2021. Zantrene still has some relevance as a chemotherapeutic in modern oncology, but its newly discovered potential is what makes this molecule so exciting, and valuable.