Date: 2017-11-03
Type of
information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the American Society of Nephrology (ASN) Kidney Week 2017
Company: Retrophin (USA - CA)
Product: sparsentan (RE-021)
Action
mechanism:
- endothelin receptor antagonist/angiotensin receptor blocker. Sparsentan has two separate mechanisms of action, acting as both an Endothelin Receptor Antagonist (ERA) and Angiotensin Receptor Blocker (ARB). Studies in similar nephropathies have shown ERAs and ARBs to both be effective in reducing proteinuria.
- Ligand Pharmaceuticals licensed worldwide rights of sparsentan (RE-021) (formerly known as DARA) to Retrophin in 2012, at the time of Retrophin’s formation.
Disease: focal segmental glomerulosclerosis (FSGS)
Therapeutic
area: Rare diseases - Kidney diseases - Renal diseases
Country:
Trial
details:
Latest
news:
- • On November 3, 2017, Retrophin announced new data from the ongoing open-label extension of the Phase 2 DUET study of sparsentan for the treatment of focal segmental glomerulosclerosis (FSGS). These data were presented during an oral session at the American Society of Nephrology (ASN) Kidney Week 2017 in New Orleans, LA.
- As previously reported, the sparsentan treatment group achieved statistical significance in the Phase 2 DUET study’s primary efficacy endpoint, demonstrating a greater than two-fold reduction in proteinuria compared to irbesartan, after an eight-week, double-blind treatment period.
- New findings from the open-label extension of the Phase 2 DUET study presented at ASN Kidney Week 2017 include:
- Patients with FSGS who remained on sparsentan for 40 weeks during the open-label period (n=38) achieved progressive reduction in proteinuria.
- In patients who received sparsentan as part of the original eight-week, double-blind treatment period (n=26), median urine protein-to-creatinine ratio (UP/C) was reduced from 2.7 g/g at baseline (week 0), to 0.7 g/g at week 48.
- Patients who crossed over to sparsentan from the original irbesartan treatment group (n=12) experienced additional and sustained reduction in proteinuria during the treatment period, with median UP/C decreasing from 2.3 g/g at crossover (week 8), to 1.7 g/g at week 48.
- The observed beneficial effects of sparsentan on proteinuria were associated with stable estimated glomerular filtration rate (eGFR).
- Transition to the sparsentan treatment group from the irbesartan group led to further reduction in proteinuria and long-term stability in eGFR.
- The observed beneficial effects of treatment with sparsentan were similar after the exclusion of data from patients who received new immunosuppression therapy during the open-label extension.
- Sparsentan continued to be generally safe and well-tolerated during the 40-week open-label extension period, including in patients who transferred from the original irbesartan group.
- Seventy-four patients continue to receive treatment with sparsentan in the ongoing open-label extension of DUET.
- • On September 7, 2016, Retrophin announced top-line results from the Phase 2 DUET study of sparsentan for the treatment of focal segmental glomerulosclerosis (FSGS). The study achieved statistical significance in the primary efficacy endpoint for the overall sparsentan treatment group, demonstrating a greater than two-fold reduction of proteinuria compared to irbesartan after the eight-week, double-blind treatment period.
- In the DUET study, the mean reduction of proteinuria from baseline after eight weeks of treatment for all patients treated with 200, 400, and 800 mg/day of sparsentan (n=64) was 44.8 percent, compared to a mean reduction of proteinuria for all patients receiving 300 mg/day of irbesartan (n=32) of 18.5 percent (p=0.006). Further, the mean reduction of proteinuria from baseline after eight weeks of treatment for all patients treated with 400 mg and 800 mg doses of sparsentan (n=51) was 47.4 percent, compared to a mean proteinuria reduction of 19.0 percent for patients receiving 300 mg of irbesartan (n=25) in these two dose cohorts (p=0.011). The comparison of individual sparsentan dose cohorts to irbesartan showed clear signals of relative improvement, but did not reach statistical significance.
- Top-line results suggest sparsentan was generally safe and well-tolerated in the DUET study. One serious adverse event, anemia, classified as potentially related to treatment occurred in the sparsentan group but did not result in study discontinuation during the eight-week blinded treatment period. There were no withdrawals due to fluid retention during the eight-week blinded treatment period. All patients who completed the eight-week treatment period entered the ongoing open label extension study, and the vast majority of these patients continue to receive therapy.
Is
general: Yes
