Rapid and Sustained Response of Biochemically Uncontrolled Acromegaly to Once-daily Oral Paltusotine Treatment

Abstract

Context Paltusotine is a nonpeptide, selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. Objective To evaluate efficacy and safety of paltusotine in patients with biochemically uncontrolled acromegaly not currently receiving medical therapy. Methods In this phase 3, randomized, double-blind, placebo-controlled trial, adults with medically untreated acromegaly at randomization (stratum 1: medication-naïve or off acromegaly medications ≥4 months [IGF-I ≥ 1.3 × upper limit of normal {ULN}]; stratum 2: controlled on a somatostatin receptor ligand and underwent washout [IGF-I increase ≥30% to ≥1.1 × ULN]) received paltusotine or placebo for 24 weeks. Results A total of 111 patients (stratum 1, n = 82; stratum 2, n = 29) enrolled (paltusotine, n = 54; placebo, n = 57). The primary endpoint of IGF-I normalization at 24 weeks was met in 55.6% of paltusotine-treated patients vs 5.3% for placebo (odds ratio [OR]: 42.81; 95% CI, 8.44-455.82; P < 1.3×ULN in 66.7% vs 14.0% of patients (OR: 18.32; 95% CI, 5.64-79.16; P < 1.0 ng/mL in 57.4% vs 17.5% (OR: 7.59; 95% CI, 2.78-23.48; P