An open-label long-term Phase 3 study of CAM2029 in patients with acromegaly (ACROINNOVA 2): interim analysis of the subgroup of patients

Diego Ferone; Spencer-Segal Joanna L.; Yaylali Guzin Fidan; Mirjana Doknic; Elena Isaeva; Alexander Dreval; Aleksandra Gilis-Januszewska; Emre Gezer; Irina Bancos; Laurence Katznelson; Maria Harrie; Agneta Svedberg; Pedroncelli Alberto M.; Fredrik Tiberg

doi:10.1530/endoabs.99.EP320

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Endocrine Abstracts (2024) 99 EP320 | DOI: 10.1530/endoabs.99.EP320

ECE2024 Eposter Presentations Pituitary and Neuroendocrinology (214 abstracts)

An open-label long-term Phase 3 study of CAM2029 in patients with acromegaly (ACROINNOVA 2): interim analysis of the subgroup of patients ‘new to CAM2029’ with controlled or uncontrolled acromegaly on standard-of-care treatment

Diego Ferone ¹ , Joanna L. Spencer-Segal ² , Guzin Fidan Yaylali ³ , Mirjana Doknic ⁴ , Elena Isaeva ⁵ , Alexander Dreval ⁶ , Aleksandra Gilis-Januszewska ⁷ , Emre Gezer ⁸ , Irina Bancos ⁹ , Laurence Katznelson 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; ²Department of Internal Medicine and Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, United States; ³Department of Endocrinology, Pamukkale University Faculty of Medicine, Denizli, Turkey; ⁴Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre Serbia, Medical Faculty of Belgrade, Belgrade, Serbia; ⁵Interregional Clinical Diagnostic Center, Kazan, Russian Federation; ⁶Endocrinology Department of Moscow Regional Research Clinical Institute, Moscow, Russian Federation; ⁷Department of Endocrinology, Jagiellonian University Medical College, Krakow, Poland; ⁸Department of Endocrinology and Metabolism, Kocaeli University Faculty of Medicine, Kocaeli, Turkey; ⁹Division of Endocrinology, Mayo Clinic, Rochester, MN, United States; ¹⁰Departments of Neurosurgery and Medicine, Stanford University School of Medicine, Stanford, CA, United States; ¹¹Camurus AB, Lund, Sweden

Background: Acromegaly, a rare, chronic disorder, results from excessive growth hormone (GH) and insulin-like growth factor 1 (IGF-1). The need for convenient therapies that provide effective disease control led to the development of CAM2029, a novel, subcutaneous, octreotide depot designed for convenient monthly self-administration using pre-filled syringes/injection pens. In a 24-week Phase 3 trial (ACROINNOVA 1, NCT04076462) CAM2029 achieved superior IGF-1 control vs placebo (72.2 vs 37.5%; P=0.0018) in patients with acromegaly controlled with standard of care (SoC; octreotide long-acting repeatable/lanreotide Autogel) at screening. Interim data from another CAM2029 Phase 3 trial (52-week, open-label [ACROINNOVA 2; NCT04125836]) are reported here, focusing on patients ‘new to CAM2029’.

Methods: ACROINNOVA 2 enrolled patients from ACROINNOVA 1 (reported separately), and ‘new to CAM2029’ patients with controlled or uncontrolled IGF-1 (≤2x upper limit of normal [ULN]) on stable SoC for ≥3 months. New patients received once-monthly CAM2029 20 mg for up to 52 weeks. The primary endpoint was adverse events (AEs). Secondary endpoints included the proportion of patients with IGF-1 ≤1x ULN (weeks 50/52 mean); the combined IGF-1/GH response; IGF-1 change from baseline; severity score of acromegaly clinical signs/symptoms, assessed using the Acromegaly Index of Severity (AIS). Baseline values reflect SoC treatment.

Results: Eighty-one ‘new to CAM2029’ patients were enrolled. At data cut-off (23 May 2023), 61 patients completed treatment at week 52, 15 were ongoing and 5 had discontinued. No new or unexpected safety signals were observed. The most common treatment-emergent AEs were injection-site reactions: ‘new to CAM2029’, 38.3%; overall population, 43%; none were Grade 3. The proportion of patients achieving IGF/GH control increased during CAM2029 treatment (Table 1). Estimated IGF-1 response (linear probability model, patients with evaluable data at weeks 50/52) increased 21.9% (95% confidence interval [CI]: 9.6, 34.1) from baseline to weeks 50/52. AIS score significantly decreased from SoC baseline to week 52 (mean of –1.3 [95% CI: –2.1, –0.5]).

Table 1. Biochemical endpoints
Endpoint	Baseline	Weeks 50/52
	n/N^all*(%)
IGF ≤x ULN (weeks 50/52 mean)	12/81 (14.8)	20/60 (33.3)
IGF ≤x ULN (weeks 50/52 mean) and GH <2.5 μg/l (week 52)	12/81 (14.8)	18/60 (30.0)
*Patients with evaluable data.

Conclusions: CAM2029 improved IGF-1/GH control and clinical symptoms in patients ‘new to CAM2029’. CAM2029 was well tolerated with a safety profile consistent with SoC. ACROINNOVA 2 reinforces the efficacy and safety of CAM2029 for treating acromegaly, including in patients with uncontrolled disease despite treatment with current SoC.