Approval for the world’s twelfth VEGF drug

How the FDA, apparently struggling with its current workload, managed to approve Takeda’s fruquintinib three weeks before its PDUFA date is almost as mysterious as why the Japanese group paid Hutchmed $400m up front for rights to the drug – the world’s 12th to target VEGF – in January. That said, as a next-generation tyrosine kinase inhibitor fruquintinib might offer greater specificity against VEGFR than most other drugs, and its approved indication, second-line colorectal cancer, is relatively uncrowded for this mechanism. A year ago Hutchmed, citing tough market conditions, announced a move to prioritise late-stage approvals to speed profitability, and Takeda stepped in to pick up ex-Asia rights to fruquintinib, now US-branded Fruzaqla. Approval is backed by the Fresco-2 trial, which yielded median overall survival of 7.4 months, versus 4.8 months for standard of care, cutting risk of death by 34% (p<0.001). The drug is already sold as Elunate in China; there it is licensed to Lilly, which turned down an option over US rights, likely because it already sells a VEGF-acting drug for colorectal cancer, namely Cyramza. Selected drugs acting on VEGFDrugCompanyMechanismUS approved cancer usesAvastinRocheMAb vs VEGFNSCLC, renal, colorectal, brain, cervical, ovarian & liverCyramzaLillyMAb vs VEGFR2Colorectal, liver, NSCLC & gastric/GEJSutentPfizerTKI vs VEGFR1, 2 & 3, PDGFR & othersRenal, GIST & pNETNexavarBayerTKI vs VEGFR1, 2 & 3, PDGFR & othersRenal, liver & thyroidFotivdaAveoTKI vs VEGFR1, 2 & 3, PDGFR & othersRenalCabometyx/ CometriqExelixisTKI vs VEGFR1, 2 & 3 & othersRenal, liver & thyroidVotrientNovartisTKI vs VEGFR1, 2 & 3, FGFR, PDGFR & othersRenalStivargaBayerTKI vs VEGFR1, 2 & 3, FGFR, PDGFR & othersColorectalLenvimaEisaiTKI vs VEGFR1, 2 & 3, FGFR, PDGFR & othersRenal, liver & thyroidCaprelsaSanofi, ex AstraZenecaTKI vs VEGFR1, 2 & 3, EGFR & othersThyroidInlytaPfizerTKI vs VEGFR1, 2 & 3RenalFruzaqlaHutchmed/ Lilly/ TakedaTKI vs VEGFR1, 2 & 32nd-line colorectal (China approved as Elunate for 3rd-line colorectal)Note: TKI=tyrosine kinase inhibitor. Source: prescribing information & scientific publications.