Patients with focal segmental glomerulosclerosis show partial remission with sparsentan
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Key takeaways:
- Overall, 42% of patients in the sparsentan group showed partial remission vs. 26% in the irbesartan group.
- There were no significant differences in the eGFR slope between the two groups.
In clinical trials, sparsentan proved more effective in reducing proteinuria vs. irbesartan in adults with focal segmental glomerulosclerosis, but there was no major change in GFR among patients on the two drugs, a study found.
In the phase 3 Duplex trial of sparsentan, a dual endothelin–angiotensin receptor antagonist, researchers randomly enrolled 371 patients, aged 8 to 75 years, with focal segmental glomerulosclerosis (FSGS) and no known secondary causes. In the study, 184 received sparsentan and 187 received irbesartan for 108 weeks. The primary endpoint was eGFR slope at final analysis.
Researchers also evaluated eGFR change from baseline to 4 weeks after the end of treatment as a subsequent objective.
At 36 weeks, 42% of patients in the sparsentan group showed partial remission of FSGS vs. 26% in the irbesartan group (P = .009). This response was sustained through the study duration.
Investigators found at the time of final analysis that there were no significant differences in the eGFR slope between the two groups. The difference in total slope between the two groups was 0.3 mL per minute per 1.73 m2 of body surface area per year.
Between-group difference in the slope from week 6 to week 108 was 0.9 mL per minute per 1.73 m2 per year, the researchers wrote.
The safety profile of sparsentan was similar to that of irbesartan.
Mean change in eGFR from baseline to week 112 was –10.4 mL per minute per 1.73 m2 with sparsentan and –12.1 mL per minute per 1.73 m2 with irbesartan, the researchers wrote.
“The change in GFR may not have been able to be seen in the sparsentan FSGS study due to the relatively short period of follow-up,” Michelle N. Rheault, MD, professor of the department of pediatrics and director of the division of pediatric nephrology at the University of Minnesota, told Healio | Nephrology News & Issues. “Because of the initial rapid decrease in GFR due to hemodynamic effects of the drug, the 2-year follow-up may not have been able to make up for that.
“Patients are being followed in an extension study; however, there is no longer a control arm after 2 years so we will lose the ability to follow up,” Rheault, the lead investigator of the trial, said.
Rheault said patients with Alport syndrome may also benefit from use of sparsentan.
“[Renin-angiotensin-aldosterone system] RAAS blockade is already well known to show benefit in this disease,” Rheault told Healio | Nephrology News & Issues. “Other endothelin receptor antagonists are currently being studied in Alport syndrome, including atrasentan. ... 27 patients with type IV collagen variants consistent with Alport syndrome were enrolled in the Duplex study, and we'll be analyzing those patients separately to see if they show benefit, although numbers will be small.”
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