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

Résumé fourni par la source

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 < .0001), with superiority to placebo in both strata. Paltusotine treatment decreased IGF-I in 92.6% of patients within the first 4 weeks. All secondary endpoints were met: mean (±SE) change in IGF-I of -0.82 ± 0.08×ULN with paltusotine vs 0.09 ± 0.08×ULN with placebo (P < .0001); IGF-I < 1.3×ULN in 66.7% vs 14.0% of patients (OR: 18.32; 95% CI, 5.64-79.16; P < .0001); GH (5-sample mean) < 1.0 ng/mL in 57.4% vs 17.5% (OR: 7.59; 95% CI, 2.78-23.48; P < .0001); mean (±SE) change in Acromegaly Symptom Diary score of -2.7 ± 1.4 vs 2.8 ± 1.4 (P = .004). Most adverse events were acromegaly symptoms or mild, transitory gastrointestinal effects characteristic of somatostatin receptor ligands (eg, diarrhea, abdominal pain). Pituitary tumor volume was stable or reduced in paltusotine-treated patients. CONCLUSION: IGF-I normalized in significantly more patients with uncontrolled acromegaly treated with paltusotine vs placebo. Paltusotine was associated with rapid, sustained IGF-I reduction, significant symptom improvement and stable or reduced pituitary tumor size and was well tolerated.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.