Drug Detail

Information about Iclusig

Generic Name	Ponatinib
IND	AP24534
Brand Name (US)	Iclusig
Manufacturer	ARIAD
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Approved for a non-GIST cancer
Indications	CML
Overall Strategy	GIST cell based
Strategy	Block related tumor signal paths
Drug Category	KIT/PDGFRA inhibitor+ VEGF inhibitor (TKI)

Ponatinib is an Bcr-Abl/KIT/VEGFR inhibitor manufactured by ARIAD. This drug is primarily being developed as a Bcr-abl inhibitor for CML. Unlike most bcr-abl inhibitors, it inhibits the T315I mutation that has been a significant cause of resistance in CML.
Phase II clinical trials are in progress for GIST (2013). Ponatinib inhibits the T670I gatekeeper secondary mutation that sometimes occurs in resistant GIST (Sunitinib and sorafenib also inhibit this mutation). It also inhibits many secondary KIT exon 17 mutations. See links below.
In the 2013 ASCO abstract, the authors concluded: PO potently inhibits the majority of clinically relevant KIT mutant kinases and has a broader spectrum of activity compared to IM (imatinib), SU (sunitinib), or RE (regorafenib). Based on these data, a phase 2 study of PO in drug-resistant GIST is ongoing.