First-in-class drugs are drugs targeting different gene products than have never successfully been targeted before for therapy. Sometimes it's because the drug target was not recognized as important until recently. Other times it's because the target is notoriously difficult to develop a valid drug for. Either way, it's usually blazing a new trail, which is both good and bad.
Zafgen was the latest potential superstar in this arena. Their Met2AP inhibitor showed first-in-class responses in the preclinical and early clinical stages for diabetes and metabolic syndrome, both of which are major markets and major unmet medical needs. The drug passed all its traditional preclinical and early clinical checks and entered clinical trials to much fanfare. Unfortunately, a patient death due to clotting (thromboembolic event) was reported. Then another one. The inevitable then ensued: the FDA put a clinical hold on the trial until the issue of whether this was a drug related problem could be resolved. Now it has been a revealed a second hold occurred after a request to test the company's follow-up candidate, ZGN-1061, in the U.S. Clinical holds cost millions of dollars as the dollars keep rolling out while the timeline for approval and financial relief moves back.
Tissue-specific adverse events are the hardest to predict and a major cause of drug attrition. Remarkably, few tools enable easy viewing of the variation of a candidate drugs targets in the various tissues of the body. Even fewer provide what Historeceptomics does, a statistical model to quantify confidence in the prediction of an unknown tissue effect.