Sparsentan could be the first FDA-approved pharmacologic treatment for focal segmental glomerulosclerosis (FSGS), a serious kidney disorder that often leads to end-stage renal disease.1

FSGS is defined by progressive scarring of the kidney and characterized by proteinuria, where protein is found in the urine due to a breakdown of the normal filtration mechanism in the kidney.2,3 The disorder is estimated to affect up to 40,000 patients in the U.S. with a similar prevalence in Europe.4

Sparsentan's dual mechanism of action combines angiotensin receptor blockade with endothelin receptor blockade. In several forms of chronic kidney disease, endothelin receptor blockade has been shown to have an additive beneficial effect on proteinuria in combination with renin-angiotensin inhibition.4,5,6,7,8,9

In late 2016, we announced positive results from the Phase 2 DUET study of sparsentan in which the overall sparsentan treatment group achieved statistical significance in the study's primary efficacy endpoint, reduction of proteinuria. The study also showed that a significantly greater proportion of patients receiving sparsentan achieved modified partial remission of proteinuria, compared to irbesartan-treated patients. Sparsentan was generally safe and well-tolerated in the study, and the incidence of adverse events was comparable across the sparsentan and irbesartan treatment groups. The most common treatment-emergent adverse events in the study were headache, hypotension, dizziness, edema, nausea, diarrhea, vomiting and upper abdominal pain.10 We are currently working with the FDA to find the most expeditious path forward for sparsentan and plan to meet with the agency in early 2017.

In 2015, the FDA and European Commission both granted sparsentan orphan drug designation for the treatment of FSGS. In the U.S., this status provides Retrophin with development and regulatory incentives, as well as seven years of marketing exclusivity, if sparsentan is approved for FSGS. Similarly, sparsentan is eligible for a single marketing authorization that is valid in all EU countries and 10 years of market exclusivity in the region, upon approval for FSGS.


Visit the National Institutes of Health clinical trial registry to learn more about the DUET study.

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  1. Middleton, et al. Nephrology Rounds 2007; 5(4).
  2. D’Agati, et al. N Engl J Med 2011;365:2398-411.
  3. The National Kidney Foundation. Focal Glomerulosclerosis. Available at: Last accessed: July 28, 2016.
  4. Data on file. San Diego, CA: Retrophin, Inc.; July 2016.
  5. Mann, et al. J Am Soc Nephrol. 2010 Mar;21(3):527-35.
  6. Weber, et al. The Lancet, Volume 374, Issue 9699, 1423-1431.
  7. Kohan, et al. J Am Soc Nephrol 22: 763–772, 2011.
  8. De Zeeuw D et al. J Am Soc Nephrol. 2014 May;25(5): 1083-1093.
  9. Dhaun, et al. Hypertension 2011; 58: e11-e12.
  10. Trachtman H, Nelson P, Radko K on behalf of the DUET Investigators. Efficacy and Safety of Sparsentan, a Dual Angiotensin II and Endothelin Type A Receptor Antagonist, in Patients with Focal Segmental Glomerulosclerosis: A Phase 2 Trial (DUET).  Presented at the American Society of Nephrology Kidney Week Meeting; November 15-20 2016, Chicago, IL.