Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement: A Randomized Clinical Trial

Abstract

Background and objectives: We assessed safety and efficacy of another somatostatin receptor analog, pasireotide long-acting release, in severe polycystic liver disease and autosomal dominant polycystic kidney disease. Pasireotide long-acting release, with its broader binding profile and higher affinity to known somatostatin receptors, has potential for greater efficacy.

Design, setting, participants, & measurements: Individuals with severe polycystic liver disease were assigned in a 2:1 ratio in a 1-year, double-blind, randomized trial to receive pasireotide long-acting release or placebo. Primary outcome was change in total liver volume; secondary outcomes were change in total kidney volume, eGFR, and quality of life.

Results: Of 48 subjects randomized, 41 completed total liver volume measurements (n=29 pasireotide long-acting release and n=12 placebo). From baseline, there were -99±189 ml/m absolute and -3%±7% change in annualized change in height-adjusted total liver volume (from 2582±1381 to 2479±1317 ml/m) in the pasireotide long-acting release group compared with 136±117 ml/m absolute and 6%±7% increase (from 2387±759 to 2533±770 ml/m) in placebo (P<0.001 for both). Total kidney volumes decreased by -12±34 ml/m and -1%±4% in pasireotide long-acting release compared with 21±21 ml/m and 4%±5% increase in the placebo group (P=0.05 for both). Changes in eGFR were similar between groups. Among the n=48 randomized, adverse events included hyperglycemia (26 of 33 [79%] in pasireotide long-acting release versus four of 15 [27%] in the placebo group; P<0.001), and among the 47 without diabetes at baseline, 19 of 32 (59%) in the pasireotide long-acting release group versus one of 15 (7%) in the placebo group developed diabetes (P=0.001).

Conclusions: Another somatostatin analog, pasireotide long-acting release, slowed progressive increase in both total liver volume/total kidney volume growth rates without affecting GFR decline. Participants experienced higher frequency of adverse events (hyperglycemia and diabetes).

Clinical trial registry name and registration number: Pasireotide LAR in Severe Polycystic Liver Disease, NCT01670110 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_28_CJN13661119.mp3.

Keywords: hepatic cyst; liver disease; polycystic kidney disease; somatostatin analog.

Copyright © 2020 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Study flow diagram. ADPLD, autosomal dominant polycystic liver disease; LAR, long-acting release; MRI, magnetic resonance imaging; TKV, total kidney volume.

Figure 2.

Liver volume changes over time. (A) Height-adjusted liver volumes from 0 to 12 months by study group and gene mutation. (B) Annualized percent change in liver volumes by study group and clinical diagnosis. ADPLD is denoted by circles, and autosomal dominant polycystic kidney disease (ADPKD) is denoted by triangles. Plus signs represent means. P values were derived from the equal variance t test comparing annualized percent change in liver volume in patients on pasireotide LAR versus patients on placebo. (C) Annualized percent change in liver volume by study group.

Figure 3.

Kidney volume changes over time. (A) Height-adjusted kidney volumes from 0 to 12 months by study group and mutation. (B) Annualized change in kidney volume by study group.

Figure 4.

Percentage of patients on pasireotide LAR on each dose level by visit month among 33 randomized patients on pasireotide LAR. AE, adverse event.