Advances in the Oral Administration of Somatostatin Receptor Ligands in Acromegaly: A Systematic Review Focusing on Biochemical Response.

Abstract

Recent advances in pharmaceutical technology, aimed at overcoming poor drug permeation across the intestinal-epithelial membrane and the challenges posed by the acidic gastrointestinal environment, have led to the development of orally administered somatostatin receptor ligands (SRLs). This development represents a promising step forward in the management of acromegaly, offering an alternative to the limitations associated with injectable SRLs. Several key clinical findings have emerged in the past two years, notably including the results from the extension phase of the MPOWERED trial, which evaluated oral octreotide capsules (OOCs), and the placebo-controlled PATHFNDR-1 trial using paltusotine. This prompted us to conduct a systematic review of the literature focusing on the efficacy of oral SRLs in controlling acromegaly, based on biochemical response. Of the 136 reports identified through our search on Medline and ClinicalTrials.gov, twelve were included, encompassing data from five interventional trials. Both OOCs and paltusotine demonstrated the ability to maintain biochemical control in patients previously controlled with injectable SRLs. While long-term maintenance was confirmed for OOCs, no data are yet available for paltusotine. Several gaps remain, such as the need for head-to-head comparisons between OOCs and paltusotine, and clinical trials in patients who have not received prior injectable SRL treatment.