A randomised phase 3 trial to assess efficacy and safety of CAM2029, an octreotide subcutaneous depot, in patients with acromegaly

Diego Ferone; Julie Silverstein; Pamela Freda; Laurence Katznelson; Federico Gatto; Pinar Kadioglu; Pietro Maffei; Jochen Seufert; Spencer-Segal Joanna L.; Elena Isaeva; Alexander Dreval; Maria Harrie; Agneta Svedberg; Fredrik Tiberg

doi:10.1530/endoabs.99.P326

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Endocrine Abstracts (2024) 99 P326 | DOI: 10.1530/endoabs.99.P326

ECE2024 Poster Presentations Pituitary and Neuroendocrinology (120 abstracts)

A randomised phase 3 trial to assess efficacy and safety of CAM2029, an octreotide subcutaneous depot, in patients with acromegaly

Diego Ferone ¹ , Julie Silverstein ² , Pamela Freda ³ , Laurence Katznelson ⁴ , Federico Gatto ¹ , Pinar Kadioglu ⁵ , Pietro Maffei ⁶ , Jochen Seufert ⁷ , Joanna L. Spencer-Segal ⁸ , Elena Isaeva ⁹ , Alexander Dreval ¹⁰ , Maria Harrie ¹¹ , Agneta Svedberg ¹¹ & Fredrik Tiberg ¹¹

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¹Endocrinology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genova, Italy; ²Division of Endocrinology, Metabolism and Lipid Research, Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States; ³Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New york, Ny, United States; ⁴Departments of Neurosurgery and Medicine, Stanford University School of Medicine, Stanford, CA, United States; ⁵Division of Endocrinology-Metabolism and Diabetes, Department of Internal Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey; ⁶Department of Medicine, Padua University Hospital, Padua, Italy; ⁷Division of Endocrinology and Diabetology, Department of Medicine II, Medical Faculty, University of Freiburg, Freiburg, Germany; ⁸Department of Internal Medicine and Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States; ⁹Interregional Clinical Diagnostic Center, Kazan, Russian Federation; ¹⁰Endocrinology Department of Moscow Regional Research Clinical Institute, Moscow, Russian Federation; ¹¹Camurus AB, Lund, Sweden

Background: Acromegaly is a rare endocrine disorder characterised by excess growth hormone (GH) and insulin-like growth factor 1 (IGF-1) that is associated with significant morbidity and impaired quality of life (QoL). Standard-of-care (SoC) treatments for acromegaly typically require healthcare provider administration, pose a substantial treatment burden, and leave scope for improved disease control. CAM2029, an octreotide subcutaneous depot with ~5x higher bioavailability than octreotide long-acting release (LAR), is designed for once-monthly self-administration as a ready-to-use syringe or injection pen. Here, we report findings from the pivotal trial of CAM2029 in patients with acromegaly.

Methods: In this Phase 3, multinational, randomised, double-blind, placebo-controlled trial (NCT04076462), patients on stable SoC treatment (octreotide LAR or lanreotide Autogel) who had IGF-1 ≤1x upper limit of normal (ULN) at screening were randomised 2:1 to once-monthly CAM2029 20 mg or placebo for 24 weeks. The primary endpoint was the proportion of patients with IGF-1 ≤ULN (mean of week 22/24 measurements). The key secondary endpoint was the proportion of patients with both IGF-1 ≤ULN (week 22/24 mean) and mean GH <2.5 µg/l (week 24). Patient-reported outcomes (PROs) were compared at baseline and week 24.

Results: Seventy-two patients were randomised to CAM2029 (n=48) or placebo (n=24). A significantly greater proportion of CAM2029 vs placebo recipients achieved the primary (IGF-1 response: 72.2% vs 37.5%; P=0.0018) and key secondary endpoints (IGF-1 and GH response: 70.0% vs 37.5%; P=0.0035). These results were supported by all sensitivity and supportive analyses. Median time to loss of response (IGF-1 >ULN) was 8.4 weeks in the placebo arm and was not reached in the CAM2029 arm. Mean IGF-1 remained below ULN throughout the study for patients receiving CAM2029 but not for patients receiving placebo. PROs showed improved QoL, treatment convenience, and patient satisfaction for CAM2029 vs baseline SoC, with numerically greater improvements vs placebo. CAM2029 was well tolerated with a comparable safety profile to SoC; no new or unexpected safety signals were observed. One treatment-related serious adverse event (cholecystitis) occurred in the placebo arm, and 5 patients discontinued treatment due to injection site erythema/induration (CAM2029: n=3; placebo: n=1) or migraine (CAM2029: n=1).

Conclusion: CAM2029 provided robust biochemical control of acromegaly superior to placebo, substantially improved PROs vs baseline SoC and placebo, and had a safety profile consistent with SoC. These findings support CAM2029 as a potential therapeutic alternative to SoC acromegaly treatments that addresses unmet patient needs.