Drug Detail

Information about Masitinib

Generic Name	Masitinib
IND	AB1010
Brand Name (US)
Manufacturer	AB Science
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Phase 3
Indications
Overall Strategy	KIT Protein Based
Strategy	Block KIT
Drug Category	KIT/PDGFRA inhibitor

Masitinib is a potent KIT and PDGFRA inhibitor. It has entered into phase III trials for first and second line treatment for GIST.
We have also seen masitinib spelled as masatinib.
In early phase I/II trials, masitinib appears to be as effective or possibly more effective (the phase III trial is needed to confirm this) than imatinib given first-line.
Masitinib is dosed based on body weight.
Phase III trialls of Masitinib (AB1010) versus Imatinib in the first line and versus sunitinib in second line are now recruiting internationally. These trials are sponsored by the manufacturer AB Science. The first-line trial is for newly diagnosed GIST patients who have not received prior TKI therapy, but may have had adjuvant Imatinib. Patients must be either non-resectable or must have a recurrence after prior surgery. Patients will be randomized to receive either Masitinib 7.5 mg/kg or Imatinib 400 or 600 mg daily. Plans call for accrual of 222 patients and a primary end point of progression free survival.
Because masitinib does not target the abl kinase or the VEGF receptors, it has been speculated that it may have less heart toxicity than other KIT TKI's.
In February 2012, AB Science issued a press release about phase II trial results in imatinib-resistant GIST. Although results in this small trial suggest a longer overall survival time, some questions remain about this. For example, if treatment with TKI's was limited beyond Sutent, this would bias the trial results.
On October 30th, 2012, an application for marketing was accepted for review of masitinib for treatment of pancreatic cancer. This was based on improved overall survival (OS) of some patients in a randomized phase III trial. Improved survival was seen in patients with an unspecified blood biomarker indicative of aggressive disease (survival improved from 5 months to 11 months in this group) and in patients presenting with a certain threshold of pain intensity (45% of patients in the trial); where OS improved by 2.7 months to 8.1 months. However, in this trial, there was no difference in overall survival when the entire patient group was analyzed.
Note: Both the phase II (GIST) and phase III pancreatic cancer EMA reviews were initially turned down. Appeals may be ongoing.