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
Project | Company | Status |
---|---|---|
Piqray | Novartis | Approved 2019 in 2nd-line HR+ve, HER2-ve, PIK3CAm breast cancer |
Inavolisib | Roche | Succeeded in ph3 Inavo-120 in 1st-line HR+ve, HER2-ve, PIK3CAm breast cancer; PDUFA date 27 Nov 2024 |
RLY-2608 | Relay Therapeutics | Ph1 breast cancer doublet (+ Faslodex) & triplet (+ Faslodex + Kisqali) data due 2024; pivotal breast cancer trial to start 2025 |
CYH33 | Haihe Biopharma | Ph2 ovarian cancer trial recruiting (China/Japan) |
Serabelisib | Faeth Therapeutics | Ph2 endometrial cancer trial not yet recruiting |
STX-478 | Scorpion Therapeutics | Ph1/2 solid tumour trial recruiting |
JS105 | Junshi Biosciences | Ph1/2 solid tumour trial recruiting (China only) |
TOS-358 | Totus Medicines | Ph1 solid tumour trial recruiting |
HS-10352 | Jiangsu Hansoh | Ph1 breast cancer trial recruiting (China only) |
BPI-21668 | Betta Pharmaceuticals | Ph1 solid tumour trial recruiting (China only) |
BBO-10203 | BridgeBio Oncology Therapeutics | Preclinical; IND had been due Q2 2024 |
LOXO-783 | Lilly | Discontinued, disclosed Aug 2024 |
Source: OncologyPipeline.
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