Lilly is down but not out of PI3K alpha inhibition

Specifically targeting the alpha isoform of PI3K has apparently helped avoid the toxicity that has dogged less selective PI3K inhibitors, but on Thursday Lilly dropped its lead contender here. The company quietly slipped into its second-quarter results presentation the discontinuation of its PI3K alpha inhibitor LOXO-783. As recently as June, during its ASCO investor event, Lilly was talking up the H1047R mutant-selective project, which was in the phase 1 Pikasso-01 trial, saying it could avoid the wild-type-mediated toxicity seen with other PI3K alpha inhibitors, including hyperglycaemia. But during its earnings call the company said it had evaluated clinical data with LOXO-783 and would now focus on a next-generation asset, which appears better and should enter human trials next year. Lilly clearly hasn’t been put off by competition in PI3K alpha inhibition; Novartis’s Piqray is approved, and Roche’s inavolisib is due an FDA approval decision by November after a triplet also containing Ibrance and Faslodex prevailed in the Inavo-120 breast cancer trial when given first line (following adjuvant therapy). The area could soon get more crowded still, with BridgeBio’s new oncology spinout set to take its contender, BBO-10203, into the clinic this year.

Selective PI3K alpha inhibitors in clinical development

Source: OncologyPipeline.