The end of Exkivity is another win for Rybrevant

The FDA has been getting tough on accelerated approvals that fail to get the backing of confirmatory trials, and last night it was Takeda’s turn to feel the pain. The group’s Exkivity got an accelerated US nod in 2021 for second-line NSCLC harbouring EGFR exon 20 insertions, but Takeda says its confirmatory Exclaim-02 trial, a phase 3 front-line study, failed to show a PFS benefit against platinum chemo, and was stopped for futility three months ago. Accordingly the group is moving to pull approvals worldwide. For doctors and patients this will be no huge loss – Exkivity had a notoriously toxic side-effect profile, carrying a warning of QTc prolongation and torsades de pointes – and it had largely been eclipsed by Johnson & Johnson’s EGFR x cMet bispecific MAb Rybrevant, whose position will thus be consolidated. Clinical discontinuations of NSCLC projects targeting the exon 20 insertion niche include Spectrum’s poziotinib and Rain Oncology’s tarloxotinib, though just last month Dizal’s sunvozertinib, a tyrosine kinase inhibitor claiming to have broad EGFR coverage, secured its first approval, in China. 

Selected projects targeting NSCLC exon 20 insertion (in EGFR unless stated)

Notes: ^EGFR x cMET bispecific; ^^MAb (all others are TKIs); *approved in China for T790M NSCLC; **includes HER2 exon 20 insertion. Source: OncologyPipeline.