Prospects for Takeda’s lung cancer candidate motesanib look bleak after a second phase III trial failed to meet its targets.
The MONET-A study, which included 400 patients with stage IV non-squamous non-small cell lung cancer (NSCLC), showed motesanib was unable to extend progression-free survival (PFS) when added to standard therapy with paclitaxel and carboplatin.
An earlier, 900-patient phase III trial of the drug reported in 2011 – called MONET-1 – also showed no improvement in PFS while patients were more likely to experience serious adverse events than those given placebo on top of paclitaxel/carboplatin.
Originally developed by Amgen, motesanib (AMG 706) is a small-molecule antagonist of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, as well as platelet-derived growth factor (PDGF) receptors and the stem cell factor (SCF) receptor.
Takeda took the decision to explore the drug’s efficacy in patients from Japan, South Korea, Taiwan and Hong Kong in MONET-A after evidence of efficacy was seen in Asian sub-populations in the initial phase III trial.
Takeda made no comment on the future status of motesanib, but with two failed trials in NSCLC and safety issues seen in earlier trials of the drug – including cardiac complications – its future now looks shaky.
Motesanib has been tested in breast, colorectal and thyroid cancer, as well as gastrointestinal stromal tumours (GIST) in the past, but according to Takeda’s latest pipeline update is not in ongoing clinical trials in any other indication but NSCLC.
Takeda licensed Japanese rights to motesanib from Amgen in 2008 for $100m upfront and $175m in potential milestone payments, and took a worldwide license to the drug in 2012 without divulging specific financial terms.