Experimental Drug More Effective in Treating Rare Kidney Disease

Rare Daily Staff

A new phase 2 study found that patients with the rare disease focal segmental glomerulosclerosis (FSGS) taking the experimental drug sparsentan saw a 45 percent reduction in proteinuria—an excess of protein in the urine that suggests poor kidney health. This compared to a 19 percent reduction in the group receiving irbesartan, the current standard of care treatment. The finding was published online October 25th in the Journal of the American Society of Nephrology.

For the new study, researchers enrolled 109 patients with FSGS, ages 8-75 in the United States and 18-75 in Europe, in a randomized, double-blind, active-controlled trial across 44 sites to assess the efficacy and safety of sparsentan. Participants were assigned either escalating doses of sparsentan (200, 400, or 800 mg per day) or irbesartan in 300 mg per day doses over eight weeks. After completing the double-blind eight-week treatment period, patients were able to continue to receive sparsentan in an open-label treatment period. Sparsentan is manufactured by Retrophin, which funded the current clinical trial.

“This is the first large-scale clinical trial of a treatment designed specifically to target FSGS, a rare disorder estimated to affect up to 40,000 people in the United States, and for which there are currently no approved therapies,” said principal investigator and lead study author Howard Trachtman, professor in the department of pediatrics at NYU School of Medicine and director of the division of pediatric nephrology at Hassenfeld Children’s Hospital at NYU Langone. Nearly half of affected patients will progress to end-stage kidney disease, he says.

With no approved treatments for FSGS, the field has sought to apply to it medications developed to treat other diseases, says Trachtman, including angiotensin II receptor blockers (ARBs) like irbesartan. Initially developed to treat high blood pressure, ARBs are currently used in lieu of an approved FSGS therapy. These drugs act by lowering the blood pressure within the filtering units of the kidney and reducing kidney scarring.

Sparsentan works as an angiotensin II receptor blocker like irbesartan, and as a blocker of the action of a second protein, endothelin receptor type A. The study authors had hypothesized that the two actions would together limit the production of molecules that lead to kidney scarring more than irbesartan’s single mechanism.

Sparsentan was found to be more effective, and also to have very few serious side effects, with the most common—low blood pressure, dizziness, and swelling—similar in both groups. The research team also found that combining effects in a single molecule increased patients’ likelihood of taking their treatment because it reduced the number of pills.

A phase III clinical trial is actively enrolling patients to determine if sparsentan brings about a sustained reduction of proteinuria. “The prevalence of FSGS is on the rise, and this combined therapy could offer new hope for patients with this rare kidney disorder who currently face a progressive decline, a high chance of end-stage kidney disease, dialysis or transplantation,” Trachtman said.

October 26, 2018

Photo: Howard Trachtman, professor in the department of pediatrics at NYU School of Medicine and director of the division of pediatric nephrology at Hassenfeld Children’s Hospital at NYU Langone