Long-term safety and efficacy of once-daily oral paltusotine in the treatment of patients with acromegaly: ACROBAT advance year 4 analysis

Gadelha Monica R.; Randeva Harpal S.; Gordon Murray B.; Mirjana Doknic; Emese Mezosi; Miklos Toth; Boguszewski Cesar Luiz; Christopher Davidson; Alessandra Casagrande; Martin Bidlingmaier; Strasburger Christian J.; Alan Krasner

doi:10.1530/endoabs.110.P973

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Endocrine Abstracts (2025) 110 P973 | DOI: 10.1530/endoabs.110.P973

ECEESPE2025 Poster Presentations Pituitary, Neuroendocrinology and Puberty (162 abstracts)

Long-term safety and efficacy of once-daily oral paltusotine in the treatment of patients with acromegaly: ACROBAT advance year 4 analysis

Monica R. Gadelha ¹ , Harpal S. Randeva ² , Murray B. Gordon ³ , Mirjana Doknic ⁴ , Emese Mezosi ⁵ , Miklos Toth ⁶ , Cesar Luiz Boguszewski ⁷ , Christopher Davidson ⁸ , Alessandra Casagrande ⁸ , Martin Bidlingmaier ⁹ , Christian J. Strasburger ¹⁰ & Alan Krasner ⁸

Author affiliations

¹Neuroendocrinology Research Center/Endocrinology Division—Medical School and Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; ²University Hospitals Coventry and Warwickshire NHS Trust, and Division of Biomedicine, Warwick Medical School, University of Warwick, Coventry, United Kingdom; ³Allegheny Neuroendocrinology Center, Allegheny General Hospital, Pittsburgh, United States; ⁴Neuroendocrine Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; ⁵Department of Medicine, University of Pécs Medical School, Pécs, Hungary; ⁶Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary; ⁷Department of Internal Medicine, Endocrine Division (SEMPR), University Hospital, Federal University of Paraná, Curitiba, Brazil; ⁸Crinetics Pharmaceuticals Inc., San Diego, United States; ⁹Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany; ¹⁰Department of Medicine for Endocrinology and Metabolism, Charité Universitaetsmedizin, Campus Mitte, Berlin, Germany

JOINT3567

Background: Paltusotine is a non-peptide, highly selective SST2 receptor agonist in development as a once-daily, oral treatment for acromegaly and carcinoid syndrome. This long-term analysis of safety and efficacy of paltusotine includes patients with acromegaly who have been followed for up to approximately 4 years.

Methods: ACROBAT Advance is an ongoing, single-arm, open-label extension study of paltusotine in patients with acromegaly. Enrolled patients had completed either ACROBAT Edge or Evolve phase 2 parent studies. In Edge, at enrollment all patients were candidates for combination drug therapy: either sub-optimally controlled on an injected SRL (octreotide or lanreotide) alone or in combination with cabergoline, or required combination therapy or pasireotide to achieve normal IGF-I levels. In Evolve, enrolled patients had normal IGF-I levels on injected SRL monotherapy. When the Advance study was initiated, paltusotine was formulated as a capsule (dose range, 10-40 mg); all patients were switched to the tablet formulation (dose range, 20-60 mg) during year 3 of the study. Adjunctive treatment with cabergoline or pegvisomant was allowed in patients who did not attain normal IGF-I levels on the maximum dose of paltusotine.

Results: Forty-three patients were enrolled in Advance (Edge, n = 32; Evolve, n = 11; 88% of eligible patients): at baseline, mean±SD age 53.0±11.6 years, 56% female, 86% previous pituitary surgery, and no prior radiotherapy. IGF-I control in Edge and Evolve subsets remained stable at parent study baseline values. For all patients pooled, median (IQR) IGF-I levels were 1.15× ULN (0.84-1.46; n = 43) at parent study baseline; in Advance, 1.14× ULN (0.89-1.29; n = 40), 1.07× ULN (0.91-1.30; n = 37), 1.02× ULN (0.83-1.21; n = 33), and 1.01× ULN (0.83-1.13; n = 20) at months 12, 24, 36, and 48, respectively. Acromegaly symptoms, as measured using Acromegaly Symptom Diary (score range, 0-70; higher values indicate greater symptom burden), were stably controlled: median (IQR) score of 8.6 (3.6-20.1; n = 21) at parent study baseline; in Advance, 10.5 (5.0-18.5; n = 40), 10.0 (5.0-23.5; n = 36), 11.0 (4.0-26.0; n = 33), and 10.0 (4.0-18.0; n = 20) at months 12, 24, 36, and 48, respectively. Two serious drug-related AEs (cholelithiasis) were reported. Of the 8 patients who discontinued study, 2 were due to AEs (mild or moderate).

Conclusion: Long-term results (up to ~4 years) show that once-daily oral paltusotine treatment was well tolerated, with stable biochemical and symptom control relative to that observed with injected SRLs.