Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine

Gadelha MR, Casagrande A, Strasburger CJ, Bidlingmaier M, Snyder PJ, Guitelman MA, Boguszewski CL, Buchfelder M, Shimon I, Raverot G, Tóth M, Mezősi E, Doknic M, Fan X, Clemmons D, Trainer PJ, Struthers RS, Krasner A, Biller BM (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Journal of Clinical Endocrinology and Metabolism Oxford University Press

Book Volume: 110

Pages Range: 228-237

Journal Issue: 1

DOI: 10.1210/clinem/dgae385

Abstract

CONTEXT: Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. OBJECTIVE: To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs). METHODS: This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had IGF-I ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0× ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary score, and maintenance of mean 5-sample GH <1.0 ng/mL. RESULTS: The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0× ULN (odds ratio, 126.53; 95% CI, 13.73->999.99; P < .0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (± SE) change in IGF-I of 0.04 ± 0.09× ULN vs 0.83 ± 0.1× ULN (P < .0001); mean (± SE) change in Acromegaly Symptom Diary score of -0.6 ± 1.5 vs 4.6 ± 1.6 (P = .02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) vs 5/18 (27.8%) patients (odds ratio, 16.61; 95% CI, 2.86-181.36; P = .0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs. CONCLUSION: Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.

Authors with CRIS profile

Michael Buchfelder Lehrstuhl für Neurochirurgie

Involved external institutions

Universidade Federal do Rio de Janeiro (UFRJ) / Federal University of Rio de Janeiro BR Brazil (BR) Crinetics Pharmaceuticals US United States (USA) (US) Charité - Universitätsmedizin Berlin DE Germany (DE) Klinikum der Universität München DE Germany (DE) Penn Medicine US United States (USA) (US) Hospital Carlos G Durand AR Argentina (AR) Universidade Federal do Paraná (UFPR) BR Brazil (BR) Rabin Medical Center / מרכז רפואי רבין‎‎ IL Israel (IL) Hospices Civils de Lyon (CHU) FR France (FR) Semmelweis University / Semmelweis Egyetem HU Hungary (HU) University of Pécs / Pécsi Tudományegyetem HU Hungary (HU) Clinical Center of Serbia RS Serbia (RS) University of North Carolina at Chapel Hill US United States (USA) (US) Massachusetts General Hospital US United States (USA) (US)

How to cite

APA:

Gadelha, M.R., Casagrande, A., Strasburger, C.J., Bidlingmaier, M., Snyder, P.J., Guitelman, M.A.,... Biller, B.M. (2024). Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine. Journal of Clinical Endocrinology and Metabolism, 110(1), 228-237. https://doi.org/10.1210/clinem/dgae385

MLA:

Gadelha, Mônica R., et al. "Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine." Journal of Clinical Endocrinology and Metabolism 110.1 (2024): 228-237.

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