Drug Overview Kinenza (enzastaurin) is an oral serine/threonine kinase inhibitor that suppresses signaling of protein kinase C (PKC)-beta to induce cell apoptosis, reduce cell proliferation, and suppress tumor-induced angiogenesis. Inhibition of PKC-beta also suppresses the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway by preventing activation and phosphorylation of AKT, glycogen synthase kinase (GSK)-3, and ribosomal protein S6.
Analyst Outlook Denovo Biopharma is developing Kinenza in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in high-risk diffuse large B-cell lymphoma (DLBCL) patients who express their proprietary, novel genetic biomarker Denovo Genomic Marker 1 (DGM1). Eli Lilly previously halted clinical development of Kinenza in DLBCL and sold the asset to Denovo after the drug failed to meet its primary endpoint in the Phase III PRELUDE trial (ClinicalTrials.gov identifier: NCT00332202). This clinical failure, in addition to limited information on the prevalence and treatment response of DGM1-positive patients, casts doubt on the renewed market potential for Kinenza in DLBCL. Data from the Phase III ENGINE study are needed to better determine the outlook for this drug.
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