Discontinued But Not Forgotten: HCV Drugs That Did Not Make It

I find it useful to look back and review drug candidates that were stopped in development.  In case of insufficient efficacy, i.e., not enough of a VL reduction or early viral rebound, everyone can sympathize with the decision to discontinue a drug.

More importantly, we want to learn about the safety problems of abandoned drug candidates.  However, here we hit a road block:  sadly this particular information is often withheld for competitive reasons.

Gentile gives us a nice summary of the 2012-2013 HCV drug ‘grave yard’ [1].  Instructive examples of late-stage disappointments include:

  • filibuvir, a non-nucleosidic NS5B drug which had a high propensity for VL rebound after drug discontinuation
  • several guanidine nucleoside NS5B inhibitors: BMS-986094, which was associated with rare cases of heart failure and kidney toxicity, IDX-184 because of concerns for similar cardiac toxicity, and PSI-938 for reasons of hepatotoxicity
  • VX-222, yet another NS5B inhibitor which was associated with a higher than expected rate of virologic break-throughs

Obviously, certain viral targets are quite a bit more difficult to tackle than others.  Case in point: the NS5B polymerase inhibitor group of drugs.  They had the highest attrition rate and ended up on the  ‘cemetery’ disproportionately often.Commandments

The authors mention that the true reasons why drugs were stopped in development are often not provided.  Too frequently, reference is made to ‘strategic decisions’ which really is another way of saying “we’ll keep you guessing”.

Bottom line: Besides company insiders, only Health Authorities know the true story, but they won’t tell.

So, where are the patient advocate groups that demand that this information be made public, as part of the patient-sponsor agreement that is the basic covenant of all clinical trials?


[1] Gentile.  Expert Opin. Investig. Drugs (2015) 24(2):239-251

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