Date: 2016-10-20
Type of information: Results
phase: 2
Announcement: results
Company: Gilead Sciences (USA - CA)
Product: selonsertib (GS-4997)
Action mechanism: enzyme inhibitor/kinase inhibitor. GS-4997 is a small-molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1 or mitogen-activated protein kinase kinase kinase 5 (MAP3K5)), which promotes inflammation, apoptosis and fibrosis in settings of increased oxidative stress associated with NASH pathogenesis. Upon oral administration, ASK1 inhibitor GS-4997 binds to the catalytic kinase domain of ASK1, thereby preventing its phosphorylation and activation. This prevents the phosphorylation of downstream kinases, such as c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (p38 MAPK). By preventing the activation of ASK1-dependent signal transduction pathways, GS-4997 prevents the production of inflammatory cytokines, down-regulates the expression of genes involved in fibrosis, suppresses excessive apoptosis and inhibits cellular proliferation.
Disease: diabetic kidney disease
Therapeutic area: Kidney diseases - Metabolic diseases - Renal diseases
Country: Canada, USA
Trial details: Study GS-US-223-1015 was a Phase 2 double-blind, placebo-controlled, dose-ranging study evaluating the efficacy, safety and tolerability of GS-4997 in 334 patients with type 2 diabetes mellitus and Stage 3 or 4 renal impairment and albuminuria. Eligible patients were randomized (1:1:1:1) to receive GS-4997 doses of 2 mg (n=81), 6 mg (n=84), 18 mg (n=84) or matching placebo (n=85) once daily on top of DKD background therapy for 48 weeks. The primary endpoint was change in estimated glomerular filtration rate (eGFR) from baseline at Week 48. (NCT02177786 )
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