Usually, saying that an experimental medicine stinks is a metaphorical statement. You know, its efficacy is marginal, or there are serious side effects. Not so for
The drug failed to meet its main goal of preventing heart attacks, strokes, and cardiovascular deaths. But when I say darapladib stunk, I'm referring to its tendency to make patients literally smell, because, according to the NEJM paper, darapladib was associated in previous studies with odor of the skin, urine, or feces. And it was true in this study, too: 19.8% of the patients on darapladib stopped taking their pills because of apparent side effects, compared to 13.5% of those on placebo. And the leading side effects were diarrhea (3.2% vs. 0.8%), feces odor (2.2% vs. 0.1%), urine odor (1.4% vs. <0.1%), and skin odor (2.2% vs. 0.1%).
What's fascinating about this is that even if darapladib had proven to be effective, this is a side effect that could have a serious impact on the product's marketability. Having a high risk of a heart attack and stroke is basically a symptom-free condition until the heart attack happens. Are patients going to take a drug that makes them smell bad? Add to this that darapladib was a curious drug development program, and an extremely risky one. With most heart drugs companies know they affect blood pressure or cholesterol or some other measure of disease. Darapladib, identified through genomics, was meant to work by lowering a marker of inflammation. It was a huge bet.
And in this study, it failed. I wonder if the number of patients who stopped taking the drug helped lead to that result, because studies like this are analyzed based on what treatment patients are assign to take, not what drugs they stayed on. The study's lead investigator, Harvey White, told Reuters: "I'm convinced there is a signal here of efficacy." Nine-point-seven patients on darapladib had a heart attack, stroke, or cardiovascular death, compared to 10.4% on placebo; that difference was not statistically significant, which means the study failed. But differences in total coronary events and serious coronary events were barely significant. Perhaps a second, ongoing study will show a benefit for the drug?
But even then, heart problems only went down by 9% or 10%. Would such a small difference be enough to lead cardiologists to prescribe a drug that will leave them fielding tons of calls from patients asking, "Doc, why do I smell so bad?"
