This Review provides a perspective on the development of non-cancer therapies based on human genetics studies and suggests measures that can be taken to streamline the pipeline from initial genetic discovery to approved therapy.
The substantial investments in human genetics and genomics made over the past three decades were anticipated to result in many innovative therapies. Here we investigate the extent to which these expectations have been met, excluding cancer treatments. In our search, we identified 40 germline genetic observations that led directly to new targets and subsequently to novel approved therapies for 36 rare and 4 common conditions.
The therapies approved for common conditions are all inhibitors designed to pharmacologically mimic the natural, disease-protective effects of rare loss-of-function variants. Large biobank-based genetic studies have the power to identify and validate a large number of new drug targets. Genetics can also assist in the clinical development phase of drugs—for example, by selecting individuals who are most likely to respond to investigational therapies.
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