Results from the Phase 3 REPRISE trial of tolvaptan in patients with autosomal dominant polycystic kidney disease showed a slower decline in estimated glomerular filtration rate compared to placebo, according to data presented at ASN Kidney Week 2017, and published in the New England Journal of Medicine.
Change in estimated eGFR from pre-treatment baseline to post-treatment follow-up, adjusted by the duration of the trial for each patient and expressed per year was -2.34 mL/min/1.73 m2 /year with tolvaptan versus -3.61 mL/min/1.73 m2/year with placebo, representing a 35% reduction of 1.27 mL/min/1.73 m2/year (95% CI 0.86 to 1.68; P<0.001).
“Tolvaptan slowed the rate of kidney function decline in this trial,” said Vicente Torres, MD, PhD, Director of the Mayo Clinic Translational Polycystic Kidney Disease Center, and lead investigator on the REPRISE trial. “These data represent a significant milestone in the investigation of this condition.”
Along with results from previous pivotal studies, findings from the REPRISE trial have formed the basis of a response to the Complete Response Letter (CRL) that FDA issued in August 2013, which Otsuka has submitted to the U.S. Food and Drug Administration (FDA) for tolvaptan as a treatment for patients with ADPKD.
About the trial
REPRISE was a Phase 3, multi-center, randomized withdrawal, placebo-controlled, double-blind trial in adult patients with late-stage 2 to early-stage 4 chronic kidney disease due to ADPKD.
After an 8-week pre-randomization period including sequential placebo and tolvaptan treatments, 1,370 ADPKD patients were randomized 1:1 to tolvaptan (90 or 120 mg per day) or placebo and treated for 12 months. The primary endpoint measured change in estimated GFR from pre-treatment baseline to post-treatment follow-up adjusted by the duration of the trial for each patient.
Otsuka collaborated on the development of the protocol for this clinical trial with the FDA through the special protocol assessment process in order to address a Complete Response Letter (CRL) issued by the agency for a New Drug Application (NDA) for tolvaptan in ADPKD in 2013. In the coming weeks the FDA will acknowledge whether the company’s response is complete and whether their regulatory review can proceed.