Tuesday, March 31, 2015

Drugs in Clinical Pipeline: Sparsentan

Sparsentan [4′-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5- dimethylisoxazol-3-yl)-2′-(ethoxymethyl)biphenyl-2-sulfonamide] is an investigational therapeutic agent which acts as both a selective endothelin receptor antagonist (ERA) and an angiotensin receptor blocker (ARB). 

Sparsentan was granted Orphan Drug Designation in January 2015 for the treatment of Focal Segmental Glomerulosclerosis (FSGS). 

Sparsentan was licensed to Retrophin, Inc. by Ligand pharmaceuticals in 2012.

Common Name: Sparsentan
Synonyms: PS433540; RE-021; DARA
IUPAC Name: 4'-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-N-(4,5- dimethylisoxazol-3-yl)-2'-(ethoxymethyl)biphenyl-2-sulfonamide
CAS Number: 254740-64-2
Mechanism of Action: Endothelin Receptor Antagonist; Angiotensin Receptor Blocker 
Indication: Treatment of Focal Segmental Glomerulosclerosis
Development Stage: Phase I/II

Company: Ligand Pharmaceuticals/Retrophin Inc

About FSCG

Focal Segmental Glomerulosclerosis (FSGS) is a rare kidney condition which is characterized by injury to the glomerular filtration barrier, which leads to progressive scarring of the glomeruli and increased levels of proteinuria. At present the standard of care for FSGS patients includes steroids and other medications such as angiotensin receptor blockers (ARBs), but there are currently no FDA-approved therapies that are specific for FSGS. Many patient with FSGS will ultimately progress to end stage renal failure and require kidney transplant or dialysis. Recent studies in several kidney diseases have shown that lowering proteinuria may be associated with improved outcomes. Sparsentan has a dual mechanism of action, acting as both an Endothelin Receptor Antagonist (ERA) and Angiotensin Receptor Blocker (ARB). Preclinical experiments as well as clinical studies have suggested that both ERAs and ARBs can be effective in reducing proteinuria.

1. ClinicalTrials.gov Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis (DUET). NCT01613118