Motesanib (AMG 706) is an experimental drug candidate originally developed by Amgen but later investigated by the Takeda Pharmaceutical Company. It is an orally administered small molecule belonging to angiokinase inhibitor class which acts as an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

VEGF receptor VEGF receptors are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Also, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR), depending on alternative splicing. Inh ...

s, platelet-derived growth factor receptors, and

stem cell factor receptor Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 (cluster of differentiation 117) or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding diff ...

s. It is used as the phosphate salt motesanib diphosphate. After clinical trials in thyroid cancer, non-small cell lung cancer, gastrointestinal stromal cancer, colorectal cancer, and breast cancer, the drug was not found to show sufficient efficacy for further development, and development was abandoned by Takeda.

Clinical trials

Motesanib was originally investigated for effectiveness against advanced nonsquamous non-small-cell lung cancer (NSCLC), with

Phase II trials The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

indicating an effectiveness comparable to

bevacizumab Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, l ...

when they were both used in combination with paclitaxel/ carboplatin. However a later and more detailed Phase III trial failed to show any benefit for the treatment of NSCLC. A second Phase III trial was started in 2012, which focused on patients from Asian backgrounds (performed on the basis of

subgroup analysis Subgroup analysis refers to repeating the analysis of a study within subgroups of subjects defined by a subgrouping variable (e.g. smoking status defining two subgroups: smokers and non-smokers). Aim The aim of subgroup analysis is usually to ass ...

) however this also failed to meet its primary endpoint. The drug has undergone a Phase II evaluation as first-line therapy for breast cancer however this study found no evidence to support further investigation. Phase II testing against persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas was also unsuccessful. Two phase II clinical trials for thyroid cancer showed promising results.

References

External links

Motesanib molecular details
{{Growth factor receptor modulators Tyrosine kinase inhibitors Nicotinamides Abandoned drugs Indolines Takeda Pharmaceutical Company brands Aminopyridines