attrition

Imagine a hundred promising compounds entering development; only a small handful will ever become approved medicines. Attrition is the name for that steady loss — the dropping out of candidates as they fail one stage after another. It is not a sign of incompetence but the central, unavoidable feature of how drug development works: most things that look promising turn out not to be.

Candidates fail for distinct reasons at different points. Early on, molecules drop for poor pharmacokinetics or unacceptable toxicity in animals. In the clinic, the dominant cause shifts toward lack of efficacy — the drug simply does not help patients enough — together with safety problems that appear only in humans and, sometimes, commercial or strategic decisions. Because the cost of each stage rises steeply, a failure in phase III hurts far more than one in discovery, which drives the industry's mantra to fail early and fail cheap by killing weak candidates before they consume the largest budgets.

Attrition is why the cost of a single approved drug is so enormous: its price tag must absorb the expense of all the siblings that died along the way. It also explains why companies maintain broad pipelines and why improving the quality of candidate selection — choosing molecules less likely to fail for predictable reasons — is one of the highest-leverage things medicinal chemistry can do.