(5.02) A Randomized Phase 3 Trial to Assess Efficacy and Safety of a Novel Formulation of Octreotide Subcutaneous Depot (CAM2029) in Patients With Acromegaly

Acromegaly is a rare endocrine disorder characterized 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, a novel subcutaneous octreotide lipid liquid-crystalline 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, randomized, 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 randomized 2:1 to once-monthly CAM2029 20 mg or placebo for 24 weeks. Primary endpoint: proportion of patients with IGF-1 ≤ULN (mean of week 22/24 measurements). Key secondary endpoint: 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 randomized 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 < ULN throughout the study for patients receiving CAM2029 but not 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).

Discussion/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.