An open-label long-term Phase 3 study of CAM2029, an octreotide subcutaneous depot, in patients with acromegaly (ACROINNOVA 2): interim analysis of the ACROINNOVA 1 roll-over patients subgroup

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; Pedroncelli Alberto M.; Fredrik Tiberg

doi:10.1530/endoabs.99.EP321

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Endocrine Abstracts (2024) 99 EP321 | DOI: 10.1530/endoabs.99.EP321

ECE2024 Eposter Presentations Pituitary and Neuroendocrinology (214 abstracts)

An open-label long-term Phase 3 study of CAM2029, an octreotide subcutaneous depot, in patients with acromegaly (ACROINNOVA 2): interim analysis of the ACROINNOVA 1 roll-over patients subgroup

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 , Alberto M. Pedroncelli ¹¹ & Fredrik Tiberg ¹¹

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¹Endocrinology United, 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 neuroendocrine disorder, characterised by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) overproduction. Persistent biochemical control to minimise adverse effects of prolonged excess GH/IGF-1 is a key treatment goal. CAM2029 is a novel octreotide depot, designed for convenient monthly subcutaneous self-administration, using pre-filled syringes/injection pens. A 24-week Phase 3 trial (ACROINNOVA 1, NCT04076462) evaluated CAM2029 in patients with acromegaly, controlled with standard of care (SoC; octreotide long-acting repeatable/lanreotide Autogel) at screening. CAM2029 met the primary endpoint, demonstrating superior IGF-1 control vs placebo (IGF-1 ≤upper limit of normal [ULN]: 72.2 vs 37.5%; P=0.0018). Interim analysis of patients who completed ACROINNOVA 1 and rolled over to the Phase 3, 52-week, open-label, long-term safety trial (ACROINNOVA 2, NCT04125836) is reported.

Methods: Patients received monthly CAM2029 20 mg for 28 weeks during ACROINNOVA 2. The primary endpoint was adverse events (AEs). Secondary endpoints included the proportion of evaluable patients with IGF-1 ≤1x ULN (weeks 50/52 mean); both IGF-1 ≤1x ULN (weeks 50/52 mean) and mean GH <2.5 µg/l (week 52); acromegaly clinical signs and symptoms severity score, assessed using the Acromegaly Index of Severity (AIS). Data are reported by treatment in ACROINNOVA 1; safety data are reported for the 52-week period.

Results: Of 64 patients completing ACROINNOVA 1, 54 entered ACROINNOVA 2 (prior-CAM2029, n=36; prior-placebo, n=18). CAM2029 was well tolerated. Fifty percent of patients (prior-CAM2029, 18/36; prior-placebo, 9/18) experienced injection-site treatment-emergent AEs (Grade ≤2). One serious treatment-related AE occurred in the prior placebo group (moderately severe cholelithiasis, resolved). In the prior-CAM2029 group, mean IGF-1 remained <ULN at weeks 50/52 in 89% of patients (Table 1). In the prior-placebo group, IGF-1 increased ≥1× ULN during ACROINNOVA 1; IGF-1 control was regained after switching to CAM2029. AIS score decreased significantly from SoC baseline to week 52 in prior-CAM2029 patients (–1.3 [95% CI: –2.3, –0.3]); in prior-placebo patients change in AIS score was –0.8 [95% CI: –2.1, 0.5]).

Table 1. Biochemical endpoints
Endpoint	Prior-CAM2029	Prior-placebo
	n/N_all* (%)
IGF ≤1x ULN (weeks 50/52 mean)	25/28 (89.3)	15/15 (100)
IGF ≤1x ULN (weeks 50/52 mean) and GH <2.5 µg/l (week 52)	23/26 (88.5)	14/14 (100)
*Patients with available data.

Conclusions: No new safety signals were observed; safety was consistent with SoC. CAM2029 provided persistent control of IGF-1/GH during treatment and improved clinical symptoms. Biochemical control of acromegaly was regained in placebo patients after switching to CAM2029.