Drug Detail

Information about Crenolanib besylate

Generic Name	Crenolanib besylate
IND	CP-868,596 (ARO-002)
Brand Name (US)
Manufacturer	Arog Pharmaceuticals
Drug Type	Tyrosine Kinase Inhibitor
Delivery	Oral
Approval Status	Phase 3
Indications
Overall Strategy	Oncogenic Signal Path Based
Strategy	Block PDGFRA
Drug Category	D842V

Crenolanib is in a phase III clinical trial for GIST patients with a mutation affecting codon D842 (primarily D842V mutations). This is a specific mutation that makes up almost 2/3 of all PDGFRA mutations. In total, this is approximately 5% of all GIST patients. See the trial link below for details about the trial.

Note: The following information comes from the manufacturers website.

ARO-002 (CP-868-596) is an orally bioavailable small molecule, highly potent, selective inhibitor of PDGFR tyrosine kinase, and it has IC50 ’s of about 1ng/mL and 0.4 ng/mL for α and β receptor types, respectively. ARO-002 is 100-fold more selective for PDGFR than for other kinases, such as c-KIT, VEGFR-2, TIE-2, FGFR-2, EGFR, erbB2, and src. In addition, crenolanib is also active in inhibiting phosphorylation of cell lines with two point mutations (double mutants) PDGFRA V561D + D842V and PDGFRA T674I + D842V.
* -- Orally bio-available
* -- Highly selective, inhibits both PDGFR-α and PDGFR-β at picomolar concentration
* -- 100-500 times more potent PDGFR-α and PDGFR-β inhibitor as compared to existing tyrosine kinase inhibitors like Imatinib , Sunitinib, etc.
* -- No activity against VEGF R1, R2, R3.
* -- Selectivity profile provides opportunity to distinguish it on basis of safety/efficacy in clinical trials
* -- Nausea, vomiting, diarrhea and high liver function test’s (LFTs) abnormalities were the most frequent treatment related AEs in Phase-1 clinical studies.
Update: August 2012 - In the phase II GIST trial, PK modeling of early patients suggested a sub-therapeutic drug level. As a result the trial protocol was amended to change the starting dose from 200 mg/day to 140 mg given twice per day.