“The Discovery of First-In-Class Drugs: Origins and Evolution”, Jörg Eder, Richard Sedrani, Christian Wiesmann2014-07-18 (biology, order statistics; backlinks)⁠:

• Here, we present an analysis of the origins of all 113 first-in-class drugs approved by the US Food and Drug Administration (FDA) 1999^–₁₄2013_11ya, which shows that:

  the majority (78) of these drugs were discovered through target-based approaches (45 small-molecule drugs and 33 biologics).

• Only 8⁄33 drugs identified in the absence of a target hypothesis were found by what we define here as ‘phenotypic screening’: the testing of a large number of compounds in a target-agnostic assay that monitors phenotypic changes.

  The discovery of the other 25 non-target-based drugs occurred through a chemocentric approach in which compounds with known pharmacology served as the starting point.

• The median time from first disclosure of the concept (target, pathway or chemotype) to FDA approval was 25 years for non-target-based drugs and 20 years for target-based drugs.

  All but 4 of the non-target-based drugs had their origins before 1985, the time around which the technologies necessary for target-based approaches were introduced.

• We conclude that target-based drug discovery is successful and recognize that high-throughput screening and other innovations applied in the past 25 years have only recently started to have a major impact on new approvals. [but see Sadri2023]

  We further suggest viewing phenotypic screening as a logical evolution of target-based approaches and consider it a novel discipline rather than a neoclassical approach.

Prior analysis of the origins of new drugs approved by the US Food and Drug Administration (FDA) 1999^–₉2008_16ya suggested that phenotypic screening strategies had been more productive than target-based approaches in the discovery of first-in-class small-molecule drugs. However, given the relatively recent introduction of target-based approaches in the context of the long time frames of drug development, their full impact might not yet have become apparent.

Here, we present an analysis of the origins of all 113 first-in-class drugs approved by the FDA 1999^–₁₄2013_11ya, which shows that:

the majority (78) were discovered through target-based approaches (45 small-molecule drugs and 33 biologics). In addition, of 33 drugs identified in the absence of a target hypothesis, 25 were found through a chemocentric approach in which compounds with known pharmacology served as the starting point, with only 8 coming from what we define here as phenotypic screening: testing a large number of compounds in a target-agnostic assay that monitors phenotypic changes.

We also discuss the implications for drug discovery strategies, including viewing phenotypic screening as a novel discipline rather than as a neoclassical approach.

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