SUN-051 CAM2029, an Octreotide Subcutaneous Depot, Provides Long-Term and Sustained Biochemical Control of Acromegaly: Final Analysis of the Core Part of the ACROINNOVA 2 Phase 3 Trial

Abstract Disclosure: J.L. Spencer-Segal: Principal investigator at trial site; received trial support from Camurus AB; advisor to Camurus AB and Crinetics Pharmaceuticals. J.M. Silverstein: Principal investigator at trial site; received trial support from Camurus AB; funding to institution from Fractyl Health, Amryt Pharma/Chiasma Pharmaceuticals/Chiesi Farmaceutici S.p.A, Ascendis Pharma, Bayer AG, Sparrow Pharmaceuticals, Recordati, AbbVie, Corcept Therapeutics, and Cortendo AB; occasional consultant for Xeris Biopharma and Camurus AB. A. Gillis-Janusewska: Principal investigator at trial site; received trial support from Camurus AB. G. Fidan Yaylali: Principal investigator at trial site; received trial support from Camurus AB. E. Isaeva: Principal investigator at trial site; received trial support from Camurus AB. M.R. Gadelha: Recipient of speaker fees from Recordati, Ipsen, Novo Nordisk A/S and Camurus AB; attended advisory boards for Novo Nordisk A/S, Recordati and Crinetics Pharmaceuticals. B. Biller: Principal investigator of institutional research grants from Crinetics Pharmaceuticals; recipient of occasional consulting honoraria from Amolyt Pharma, Camurus AB, Chiesi Farmaceutici S.p.A, Crinetics Pharmaceuticals, Pfizer and Recordati. P. Maffei: Principal investigator at trial site; received trial support from Camurus AB. M. Fleseriu: Recipient of institutional grants from Crinetics Pharmaceuticals and occasional scientific consulting honoraria from Amolyt Pharma, Camurus AB, Crinetics Pharmaceuticals, Debiopharm, Novo Nordisk A/S, and Recordati. A.M. Pedroncelli: Employee and shareholder of Camurus AB. J. Råstam: Employee and shareholder of Camurus AB. M. Harrie: Employee and shareholder of Camurus AB. A. Svedberg: Employee and shareholder of Camurus AB. F. Tiberg: Employee and shareholder of Camurus AB. D. Ferone: Principal investigator at trial site; received trial support from Camurus AB; consultant for, and research grants received from, Camurus AB, Ipsen, Novartis-AAA and Recordati. Background: Acromegaly is characterized by overproduction of growth hormone and insulin-like growth factor-I (IGF-I). Biochemical control is crucial to improve symptoms and comorbidities. CAM2029, developed using FluidCrystal® technology, is a long-acting octreotide subcutaneous depot designed for convenient self-administration via an autoinjector pen. In ACROINNOVA 1, a 24-week (W), Phase 3 trial (NCT04076462), CAM2029 achieved superior biochemical control vs placebo (PBO; 72.2% vs 37.5%; P=0.0018) in patients previously controlled on standard of care (SoC; octreotide long-acting repeatable [LAR]/lanreotide Autogel [ATG]). ACROINNOVA 2 (NCT04125836) assessed long-term safety and efficacy; we report the final analysis of the trial’s core phase. Methods: ACROINNOVA 2, a 52-W, Phase 3, open-label trial (with 52-W extension), directly enrolled new patients with IGF-I ≤2×upper limit of normal (ULN) on SoC for ≥3 months and patients completing ACROINNOVA 1 (prior-CAM2029 and prior-PBO groups). Patients received CAM2029 20 mg every 4 W (±1 W) for 52 W (W24−52 for prior-PBO). The primary endpoint was characterization of adverse events (AEs). Secondary endpoints included the proportion of patients with biochemical control (IGF-I ≤ULN; W50/52 mean) and the severity of acromegaly signs/symptoms (Acromegaly Index of Severity [AIS] score) over time. Results: ACROINNOVA 2 enrolled 135 patients: 81 patients directly and 54 roll-over patients who completed ACROINNOVA 1 (prior-CAM2029, n=36; prior-PBO, n=18). Seventy-four and 53 patients in the directly enrolled and roll-over groups completed treatment, respectively. CAM2029 was well tolerated; no new or emerging safety issues were identified. Most AEs were mild to moderate (Grade 1−2). The most common AEs were injection site erythema, injection site swelling and COVID-19. New injection site-related AEs decreased throughout the study. No severe (Grade 3) AEs were deemed related to CAM2029. IGF-I control in directly enrolled patients was 14.8% (12/81) at baseline and 36.5% (27/74) at W50/52. At W50/52, IGF-I control was maintained in 88.6% (31/35) of prior-CAM2029 patients; 94.4% (17/18) of prior-PBO patients regained IGF-I control with CAM2029 treatment. In the overall population, mean AIS overall scores improved from baseline to W52 (−1.2 [95% confidence intervals: −1.7, −0.6]). Conclusions: Long-term treatment with CAM2029 demonstrated a safety profile consistent with injectable octreotide LAR and lanreotide ATG. CAM2029 notably improved the rate of biochemical control in directly enrolled patients with previously uncontrolled disease on SoC, provided sustained control in prior-CAM2029 patients, and returned control to prior-PBO patients. The symptom burden also progressively improved with CAM2029. These results reinforce previous findings, supporting CAM2029 as a new treatment option for acromegaly. Presentation: Sunday, July 13, 2025