Lanreotide 90mg/0.5ml solution for injection pre-filled syringes

ContextThere are limited head-to-head trials comparing pharmacological treatments for acromegaly.ObjectiveSystematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a network meta-analysis (NMA) enabling indirect comparisons.MethodsMEDLINE and Embase were searched to identify randomized controlled trials (RCTs) of acromegaly therapies. Screening and data extraction followed PRISMA guidelines. Feasibility assessment evaluated homogeneity and consistency assumptions required for NMA. Bayesian NMAs estimated relative treatment effects and ranking probabilities.ResultsTwenty-two records covering 18 RCTs were included. Biochemical control rates were comparable among long-acting injectable somatostatin receptor ligands (SRLs), including lanreotide autogel (LAN-ATG), octreotide long-acting release (OCT-LAR), pasireotide, the GH receptor antagonist pegvisomant, oral octreotide (O-OCT), octreotide subcutaneous depot (SC-OCT-D), and the once-daily oral SRL paltusotine. Paltusotine demonstrated significantly higher biochemical control vs O-OCT and SC-OCT-D (odds ratios [ORs], 95% credible intervals [CrIs]: 7.34 [1.48-36.07] and 7.85 [1.72, 36.25]). Pasireotide showed significantly higher biochemical control vs OCT-LAR (OR: 2.03 [1.29-3.23]). Paltusotine had significantly lower discontinuations due to adverse events (AEs) vs O-OCT and SC-OCT-D, (ORs: 0.022 [0.001-0.424] and 0.022 [0.001-0.343]), with similar rates to other treatments. Treatment-emergent AEs (TEAEs) and serious TEAEs were comparable across treatments. Rankings suggested paltusotine as the treatment with the highest probability of ranking as the most effective (or tolerable) treatment across all endpoints studied.ConclusionThis systematic review and NMA consolidate recent high-quality RCT evidence for acromegaly treatments. Paltusotine emerges as a promising alternative to injectable SRLs, with favorable efficacy, safety, and AE-related discontinuation patterns. These findings may inform clinical decision-making and guideline development, if confirmed by clinical experience.

Abstract licence: CC BY

ContextAcromegaly, characterized by excessive GH and insulin-like growth factor-1 (IGF-1), impacts quality of life (QoL) and mortality. Standard of care (SoC; octreotide long-acting repeatable or lanreotide autogel) treatment typically requires healthcare provider administration. CAM2029, a novel subcutaneous octreotide depot with increased bioavailability using FluidCrystal technology, enables self-administration and room-temperature storage.ObjectiveAssess superiority of CAM2029 vs placebo for biochemical control in patients with controlled acromegaly.Design24-week, multinational, randomized, double-blind, phase 3 trial (NCT04076462).Setting45 sites; 10 countries.Patients72 patients on SoC with biochemical control at screening [IGF-1 ≤upper limit of normal (ULN); mean GH InterventionsPatients were randomized 2:1 to once-monthly CAM2029 (n = 48) or placebo (n = 24).Main outcome measuresThe primary endpoint was proportion of patients with IGF-1 ≤ULN (week 22/24 mean), with dose-reduced patients classified as nonresponders; first key secondary endpoint was the same, including dose-reduced responders. The second key secondary endpoint was proportion of patients with IGF-1 ≤ULN (week 22/24) and mean GH ResultsAt week 22/24 (intention-to-treat analysis), CAM2029-treated patients demonstrated superior response rates vs placebo for IGF-1 (72.2% vs 37.5%; risk difference: 34.6, 95% confidence interval: 11.3, 57.9; P = .0018) and combined IGF-1/GH (70.0% vs 37.5%; P = .0035). CAM2029-treated patients had well-controlled symptoms, improved QoL, and treatment satisfaction vs placebo and baseline. CAM2029 was well tolerated; safety was consistent with SoC.ConclusionCAM2029 provides a convenient and effective treatment option for acromegaly, with superior biochemical control vs placebo. Symptom control, QoL, and satisfaction were improved from baseline SoC.Clinical trial registrationNCT04076462 (ClinicalTrials.gov).

Abstract licence: CC BY