OR01-01 Oral, Once-daily, Paltusotine (Non-peptide Selective Somatostatin Receptor Subtype 2 Agonist) Therapy In Patients With Acromegaly Is Associated With Long-term Biochemical And Symptom Control And Is Preferred Over Injectable Somatostatin-Receptor Ligands

Disclosure: M.R. Gadelha: Advisory Board Member; Self; Crinetics Pharmaceuticals, Ipsen, Novo Nordisk, and Recordati Rare Diseases. Research Investigator; Self; Crinetics Pharmaceuticals and Recordati Rare Diseases. Speaker; Self; Crinetics Pharmaceuticals, Ipsen, Novo Nordisk, and Recordati Rare Diseases. H.S. Randeva: None. M.B. Gordon: Consulting Fee; Self; Crinetics Pharmaceuticals, HRA Pharma, Novo Nordisk, and Recordati Rare Diseases. Grant Recipient; Self; Ascendis, Camurus, Chiasma, Corcept, Crinetics, Ipsen, Novartis, Novo Nordisk, Opko, Pfizer, and Strongbridge. M. Doknic: Advisory Board Member; Self; Pfizer in CEE region. Research Investigator; Self; Crinetics Pharmaceuticals, Pfizer, Camurus, Ascendis, Opko, Ipsen, and Teva. Speaker; Self; Pfizer, Novartis, Novo Nordisk, Sandoz, and Merck. E. Mezosi: Research Investigator; Self; Crinetics Pharmaceuticals. M. Toth: Consulting Fee; Self; Ipsen, Novartis, Pfizer, and Recordati Rare Diseases. Research Investigator; Self; Crinetics Pharmaceuticals. C.L. Boguszewski: Consulting Fee; Self; Novo Nordisk. Research Investigator; Self; Crinetics Pharmaceuticals and Recordati Rare Diseases. Speaker; Self; Ipsen and Recordati Rare Diseases. C.T. Ferrara-Cook: Employee; Self; Crinetics Pharmaceuticals. A. Casagrande: Employee; Self; Crinetics Pharmaceuticals. A. Krasner: Employee; Self; Crinetics Pharmaceuticals. Paltusotine is an investigational oral, once-daily, non-peptide, SST2 agonist in development for the treatment of acromegaly and neuroendocrine tumors. Interim analysis results from patients with acromegaly treated with paltusotine for up to 2 years in ACROBAT Advance (NCT04261712), an ongoing, 4-year, single-arm, open-label extension study, are reported here. Patients who completed ACROBAT Edge (NCT03789656) or Evolve (NCT03792555) phase 2 parent studies were eligible to enroll in Advance. In Edge, patients were either sub-optimally controlled on injectable somatostatin-receptor ligand (iSRL; octreotide or lanreotide) therapy alone or in combination with cabergoline; or required combination therapy or pasireotide to achieve normal IGF-I levels at baseline. Evolve enrolled patients who had normal IGF-I levels on iSRL monotherapy at baseline. In Advance, adjunctive medication with cabergoline or pegvisomant was allowed in patients who had not achieved normal IGF-1 levels on maximum dose of paltusotine (40 mg). Serum IGF-I levels were measured using Immunodiagnostic Systems iSYS immunoassay. Symptoms were assessed using the Acromegaly Symptom Diary (ASD; score range, 0-70; higher numbers indicate greater symptom burden), which was developed based on FDA recommendations for patient-reported outcome tools. Patient treatment preference was also evaluated. Forty-three patients were enrolled in Advance (Edge, n=32; Evolve, n=11; 88% of eligible patients). At baseline on iSRL, mean (SD) age was 53.0 (11.6) years, 56% were females, 86% had previous pituitary surgery, and none had radiotherapy. Median (IQR) IGF-I levels remained stable: baseline on iSRL, 1.15x ULN (0.84, 1.46; n=43); in Advance, Week 51 1.08x ULN (0.87, 1.26; n=37), Week 77 1.01x ULN (0.85, 1.28; n=27), and Week 103 1.10x ULN (0.96, 1.45; n=10). Among patients receiving adjunctive medication in Advance, 94% were from the Edge study. Acromegaly symptoms were stably controlled: median (IQR) ASD scores at baseline on iSRL, 8.57 (3.57, 20.14; n=21) and, in Advance at Week 77, 8.0 (5.0, 18.0; n=14). At Week 52, 32 (88.9%) of the 36 respondents preferred once-daily oral paltusotine, 2 (5.6%) preferred previous injections, and 2 (5.6%) had no preference. The most common treatment-emergent adverse events (TEAEs) reported were headache (30.2%), arthralgia (25.6%), and fatigue (18.6%). No serious drug-related TEAEs were reported. Of the 6 patients who discontinued the study, 1 (2.3%) was due to a TEAE (headache). Glycemic control, as measured by HbA1c, was stable during paltusotine treatment. In conclusion, with up to 2 years of follow-up in patients with acromegaly, once-daily oral paltusotine treatment was well-tolerated, associated with stable IGF-I and symptom control relative to that achieved by iSRLs, and was preferred over injected therapy. Support: Crinetics Pharmaceuticals. Presentation: Thursday, June 15, 2023