The recent failure of AstraZeneca’s interleukin-13 (IL-13) inhibitor tralokinumab to show efficacy in two phase 3 trials in asthma extends an already lengthy rap sheet against a therapeutic target that has confounded drug developers’ expectations. Despite widespread recognition of the central role IL-13 plays in mediating allergic disease, companies have struggled for more than a decade to produce clear-cut clinical evidence that targeting the cytokine will benefit patients. The field is littered with molecules that have failed mid-and late-stage trials in numerous indications (Table 1). Only one drug has emerged successfully from the pack, the dual IL-4 and IL-13 signaling inhibitor Dupixent (dupilumab). Made by Paris-based Sanofi and Tarrytown, New York–based Regeneron Pharmaceuticals, Dupixent gained approval last year for treating atopic dermatitis, a form of eczema, and is poised to secure an additional approval in asthma, following a positive read-out from two recent phase 3 trials (Nat. Biotechnol. 35, 391–392, 2017). But apart from that exception, the drug industry’s interest in IL-13 could amount to nothing more than a very expensive write-off unless Dermira, of Menlo Park, California, and Leo Pharma, of Ballerup, Denmark, succeed in dermatology conditions.“We don’t think the game is over by any means for IL-13,” says Luis Peña, co-founder and chief development officer of Dermira, which last year in-licensed the anti-IL13 antibody lebrikizumab from Basel, Switzerland–based Roche in a deal involving $135 million in upfront and near-term milestone payments.