Tolvaptan for Treatment of Patients With ADPKD in the Republic of Korea Safe and Effective

In 2015, the Korean Food and Drug Administration approved tolvaptan to treat patients with autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan is a selective vasopressin V2 receptor antagonist.

During a poster session at ASN Kidney Week 2024, Hayne C. Park and colleagues presented results from the ESSENTIAL study, a phase 4 clinical trial designed to assess the safety and effectiveness of tolvaptan among patients in Korea with ADPKD and CKD stages 1 to 3. The poster was titled Evaluating the Safety and Effectiveness in Adult Korean Patients Treated With Tolvaptan for Management of Autosomal Dominant Polycystic Disease (ESSENTIAL): Final Report.

The study included 117 patients in Korea with rapidly progressing ADPKD, ranging in age from 19 to 50 years. Tolvaptan was prescribed for 24 months, with the maximum tolerable dose up to 120 mg per day. The primary outcome of interest was the incidence of treatment emergent adverse events, including hepatic adverse events. Secondary outcomes included annual mean percent change of total kidney volume (TKV) and annual mean change of eGFR.

Of the 117 participants, 90.6% (n=106) experienced a treatment emergent adverse event (n=489). During the study period, there were 17 cases of hepatic adverse events (14.5%); those occurred primarily within the first 18-month period. Following discontinuation of the drug, liver enzymes were normalized. The frequency of hepatic adverse events was higher among patients with a previous history of liver disease and those with mild elevation of liver enzyme (a finding that did reach statistical significance).

Tolvaptan attenuated both TKV growth and rate of eGFR decline compared to the calculated predicted value.

“Although the incidence of hepatic adverse events was higher in Korean ADPKD patients compared with the previous studies, tolvaptan can be prescribed safely and effectively using meticulous titration and 1-month interval monitoring,” the researchers said.

Source: Park HC, Kim YC, Jung Y, Kim Y, Oh YK. Evaluating the safety and effectiveness in adult patients treated with tolvaptan for management of autosomal dominant polycystic kidney disease (ESSENTIAL): final report. TH-PO444. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2024; October 24, 2024; San Diego, California. Funding for this study was provided by Korea Otsuka Pharmaceuticals.