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Cardiovascular Disease

Defibrillating Dalcetrapib

In 2012, Roche halted development of their CETP inhibitor dalcetrapib, part of what (so far) has been a grim chapter in cardiovascular drug development. At the time, this was put down to lack of efficacy, rather than the bad effects seen with Pfizer’s torcetrapib, news that did nothing to cheer up the CETP research community.
Now DalCor (of Montreal) has licensed the compound, and is planning to go back into the clinic. What makes them think that they’ll have any better time of it? The plan is to restrict the clinical trial (and the eventual patient population) to a group that appears to be genetically predisposed to respond. An analysis of the trial data suggests that polymorphisms in the ADCY9 gene (adenylate cyclase 9) could account for large variations in the effects of dalcetrapib. DalCor and the Montreal Heart Institute plan to screen about 30,000 potential patients to find enough of them with the right profile.
What’s not clear to me is how many potential patients (and customers) this polymorphism leaves you with. DalCor has apparently run the numbers, and believes that there’s potential here but (naturally) this also all depends on that analysis from the previous trials being solid. Dalcetrapib will never be the blockbuster that Roche hoped for some years ago, but just turning it into a drug at all would (by this point) make for quite a story.

3 comments on “Defibrillating Dalcetrapib”

  1. Big Richard says:

    I have a feeling in licensing a drug on the basis of a post hoc analysis is a really poor idea.

  2. Old man says:

    Just think about how many “failed” drugs could be revived with the right screening tests to predict adverse side effects. Profile the patient first / prescribe second. Easier said than done, but doable?

  3. HFM says:

    @2: Absolutely doable, especially with human genomes approaching the $1K mark. It’s already having an impact in cancer therapy.
    One story I heard about Gleevec – when it entered the market, they tried it on many tumor types, because why not. Most of the trials failed, but gastric stromal tumors seemed to respond. They eventually figured out why (off-target effects on the related kinase KIT), then went looking for other tumors with KIT mutations. Apparently about 1 in 30 melanomas is KIT-dependent, and if you find these people and give them Gleevec, they do absurdly well (by melanoma standards). There’s so few of them that a standard trial would (and did) fail, but when it works, it works well.
    The trick is to have some idea what you’re looking for. Otherwise you’re going to wander in the wastelands of post-hoc rationalization, chasing statistical ghosts.

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