Another PI3K inhibitor bites the dust

The troubled PI3K inhibitor space has had another setback: Bayer is withdrawing Aliqopa in follicular lymphoma after the failure of the confirmatory Chronos-4 trial, the company confirmed to ApexOnco today. During its quarterly results yesterday Bayer said it was discontinuing Aliqopa, which it previously pulled in non-Hodgkin’s lymphoma. The news comes after various withdrawals and discontinuations for the class, which has been dogged with toxicity concerns. Gilead’s Zydelig still seems to be selling, albeit not much, while the future of Secura Bio’s Copiktra looks in doubt following an FDA adcom last year voting against its approved use of chronic lymphocytic leukemia and small lymphocytic lymphoma. While Secura seems to be holding out, others to have thrown in the towel include MEI Pharma and Kyowa Kirin, which last year discontinued development of their project, zandelisib, outside Japan. There are a handful of mid to early-stage contenders still standing, but hopes cannot be high that these will make any mark in the US.  PI3K inhibitors in haematological cancersCompanyProjectPharmacologyIndicationStatusMarketedGilead Sciences ZydeligPI3K delta 2nd-line CLL (Rituxan combo)Full approval Jul 2014, PFS benefit vs Rituxan3rd-line FL & SLLAccelerated approval Jul 2014; withdrawn Jan 2022Secura Bio (via Verastem)CopiktraPI3K delta & gamma3rd-line CLL & SLLFull approval Sep 2018; FDA adcom voted 8-4 against this use in Sep 20223rd-line FLAccelerated approval Sep 2018; withdrawn Dec 2021Withdrawn/discontinuedBayer AliqopaPan-PI3K3rd-line FLAccelerated approval Sep 2017; withdrawn Nov 2023 after confirmatory Chronos-4 trial failed2nd-line indolent NHL (Rituxan combo)Filed May 2021, withdrawn Dec 2021MEI Pharma/ Kyowa KirinZandelisibPI3K delta 3rd-line+ FLDiscontinued outside Japan Dec 2022TG Therapeutics (ex Rhizen)UkoniqPI3K delta 2nd-line MZL & 4th-line FL Accelerated approval Feb 2021, withdrawn Apr 2022Incyte ParsaclisibPI3K delta 3rd-line+ FL & othersDiscontinued Jan 2022Rhizen PharmaceuticalsTenalisibPI3K delta & gamma1L PTCL (chemo combo)Trial withdrawn; focus now seems to be on breast cancerPhase 2HutchmedAmdizalisibPI3K deltar/r MZL & FLUncontrolled China study; topline data due H2 2023Shanghai Yingli/ Jiangsu HengRuiLinperlisibPI3K delta T/NK cell lymphomaApproved for r/r FL & filed for r/r PTCL in ChinaPhase 1IoncturaRoginolisib (IOA-244)PI3K deltaNHL & solid tumours (Dione-01)Early trial of monoRx or chemo combo; final data due Q1 2024BeiGeneBGB-10188PI3K deltaB-cell cancersEarly trial of monoRx or combosNotes: FL=follicular lymphoma; MZL=marginal zone lymphoma; SLL=small lymphocytic leukaemia; CLL=chronic lymphoblastic leukaemia; NHL=non-Hodgkin's lymphoma; PTCL=peripheral T-cell lymphoma. Source: OncologyPipeline & company communications.