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 cancers
| Company | Project | Pharmacology | Indication | Status |
|---|---|---|---|---|
| Marketed | ||||
| Gilead Sciences | Zydelig | PI3K delta | 2nd-line CLL (Rituxan combo) | Full approval Jul 2014, PFS benefit vs Rituxan |
| 3rd-line FL & SLL | Accelerated approval Jul 2014; withdrawn Jan 2022 | |||
| Secura Bio (via Verastem) | Copiktra | PI3K delta & gamma | 3rd-line CLL & SLL | Full approval Sep 2018; FDA adcom voted 8-4 against this use in Sep 2022 |
| 3rd-line FL | Accelerated approval Sep 2018; withdrawn Dec 2021 | |||
| Withdrawn/discontinued | ||||
| Bayer | Aliqopa | Pan-PI3K | 3rd-line FL | Accelerated approval Sep 2017; withdrawn Nov 2023 after confirmatory Chronos-4 trial failed |
| 2nd-line indolent NHL (Rituxan combo) | Filed May 2021, withdrawn Dec 2021 | |||
| MEI Pharma/ Kyowa Kirin | Zandelisib | PI3K delta | 3rd-line+ FL | Discontinued outside Japan Dec 2022 |
| TG Therapeutics (ex Rhizen) | Ukoniq | PI3K delta | 2nd-line MZL & 4th-line FL | Accelerated approval Feb 2021, withdrawn Apr 2022 |
| Incyte | Parsaclisib | PI3K delta | 3rd-line+ FL & others | Discontinued Jan 2022 |
| Rhizen Pharmaceuticals | Tenalisib | PI3K delta & gamma | 1L PTCL (chemo combo) | Trial withdrawn; focus now seems to be on breast cancer |
| Phase 2 | ||||
| Hutchmed | Amdizalisib | PI3K delta | r/r MZL & FL | Uncontrolled China study; topline data due H2 2023 |
| Shanghai Yingli/ Jiangsu HengRui | Linperlisib | PI3K delta | T/NK cell lymphoma | Approved for r/r FL & filed for r/r PTCL in China |
| Phase 1 | ||||
| Ionctura | Roginolisib (IOA-244) | PI3K delta | NHL & solid tumours (Dione-01) | Early trial of monoRx or chemo combo; final data due Q1 2024 |
| BeiGene | BGB-10188 | PI3K delta | B-cell cancers | Early trial of monoRx or combos |
Notes: 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.
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