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Tolvaptan slows kidney function decline
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In patients with later-stage autosomal dominant polycystic kidney disease, tolvaptan reduced the estimated glomerular filtration rate by 35% compared with placebo, according to research presented at American Society of Nephrology Kidney Week 2017.
A previous clinical trial, TEMPO 3:4, showed that the vasopressin V2 receptor antagonist tolvaptan reduced the rate of kidney growth and the estimated glomerular filtration rate (eGFR) in patients with early autosomal dominant polycystic kidney disease (ADPKD), Vicente E. Torres, MD, PhD, from Mayo Clinic, told Healio Internal Medicine.
The eGFR benefit was maintained after 2 years in an extension of the TEMPO 3:4 trial (TEMPO 4:4), he said. However, elevations of transaminase and bilirubin were more common with tolvaptan than placebo, he said.
“The REPRISE trial was performed to determine the efficacy and safety of tolvaptan in more advanced ADPKD (eGFR between 25 and 65 mL/min/1.73 m2) with monthly monitoring of liver enzymes,” Torres said.
Torres and colleagues enrolled 1,370 patients with later-stage ADPKD aged between 18 and 55 years with an eGFR between 15 and 65 mL/min/1.73 m² or aged between 56 and 65 years with an eGFR between 25 and 44 mL/min/1.73 m² in the phase 3, multicenter, randomized withdrawal, placebo controlled, double blind trial.
The researchers conducted a prerandomization period with sequential placebo and tolvaptan treatments for 8 weeks. Then they randomly assigned participants to receive either tolvaptan or placebo for 12 months. The safety of the drugs was assessed each month.
Data showed that patients treated with placebo achieved an annualized eGFR change of –3.61 mL/min/1.73 m² while those treated with tolvaptan had an annualized eGFR change from pretreatment baseline to post-treatment follow-up of –2.34 mL/min/1.73 m², a 35% reduction in the rate of eGFR decline.
The annualized eGFR slope was –3.16 mL/min/1.73 m² for tolvaptan and –4.17 mL/min/1.73 m² for placebo.
A total of 5.6% and 1.2% of participants receiving tolvaptan or placebo, respectively, demonstrated an increase of more than three times the upper limit of normal of alanine aminotransferase levels. Although transaminase elevations were more common in patients treated with tolvaptan, they were reversible after withdrawal of treatment. Bilirubin elevations of more than two times the upper limit of normal were not observed.
“The results of REPRISE over 1 year in patients with later stage disease, together with those of TEMPO 3:4 and TEMPO 4:4 over 5 years in early stage disease, show that tolvaptan is effective over a broad range of disease and may delay the need for dialysis or kidney transplantation,” Torres said. – by Alaina Tedesco
Reference:
Torres VE, et al. Tolvaptan slows eGFR decline in later-stage ADPKD. Presented at: American Society of Nephrology Kidney Week 2017; Oct. 31-Nov. 5; New Orleans.
Disclosure: Torres reports being a member of the Steering Committee for the TEMPO and REPRISE trials for Otsuka and a consultant for Vertex, Sanofi-Genzyme and Palladio.