ForePass replicates effects of bariatric surgery and outperforms GLP-1

The ForePass endoscopic metabolic bypass platform reproduced insulin sensitivity levels observed following biliopancreatic diversion (BPD) while substantially outperforming semaglutide (Ozempic/Wegovy) in weight control in a randomised preclinical study, according to a study led by Professor Ivo Boskoski, Professor of Digestive Endoscopy at Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Lazio, Italy.

ForePass endoscopic metabolic bypass platform

 “This study demonstrates that ForePass reproduced metabolic effects typically associated only with highly invasive metabolic surgery through a minimally invasive and fully reversible endoscopic approach,” said Boskoski. “The magnitude of the insulin sensitivity improvements and glycaemic control observed in this model is remarkable.”

ForePass is an innovative device that combines a funnel-shaped gastric balloon linked to an intestinal sleeve, which according to the device’s manufacturer Keyron, effectively replicates the mechanism of metabolic surgery without the need for surgery or making any incisions. The device is inserted into the stomach and proximal intestine using endoscopy, a less invasive and cheaper procedure compared to metabolic surgery. Unlike metabolic surgery, ForePass is fully reversible, making it an appealing option, especially considering that the vast majority of patients with metabolic diseases reject invasive surgery.

The ForePass device links the stomach to the jejunum via a gastric funnel connected to an intestinal sleeve. The balloon, which reduces the gastric volume by approximately 2/3, is traversed by a central channel that connects to the sleeve, which extends through the duodenum and proximal jejunum. subsequently, ingested foods bypass the duodenum and proximal jejunum arriving directly into the mid-jejunum.

Figure 2: Characteristics of the Forepass device. (A) The overall structure of the ForePass device, which is composed of a silicone gastric balloon and an expanded polytetrafluoroethylene (EPTFE) intestinal sleeve. A nitinol stent-like funnel, which traverses the balloon, connects to the sleeve. The transplyloric stent, coated by EPTFE, helps to improve device stability. (B) An endoscopic image of the proximal end of the ForePass device, including the inflated gastric balloon. The balloon’s colour is due to methylene blue added to the saline solution used to inflate the device. (C) An X-ray fluoroscopy image of the ForePass device positioned in the stomach and proximal gut. The balloon component of the device is placed in the stomach, while the transpyloric stent and intestinal sleeve are located further down, past the pylorus. Credit: Gut (2023). DOI: 10.1136/gutjnl-2023-331335

“For decades, BPD has demonstrated the metabolic impact of excluding the proximal intestine, but its invasiveness has limited adoption. ForePass is exciting because it seeks to reproduce these mechanisms through a minimally invasive, reversible endoscopic approach,” added Professor Geltrude Mingrone, Professor of Diabetes at King's College London. “The insulin-sensitivity improvements observed in this large-animal study support advancing toward human trials.”

In the study, 12 young Landrace pigs underwent ForePass implantation, semaglutide treatment or sham endoscopy with a one-month follow-up period. ForePass limited weight gain to +4.3%, compared with +36% in semaglutide-treated pigs and +47% in controls, without affecting linear growth. Food intake decreased by 26% with ForePass versus 18.5% with semaglutide. The device induced a near-flat glycaemic response and markedly improved insulin sensitivity (SI=2.75±0.37 pM⁻¹·min⁻¹), while semaglutide and sham produced only modest effects.

ForePass reproduced insulin sensitivity levels previously observed following biliopancreatic diversion while outperforming semaglutide by more than eight-fold in weight control in a randomized preclinical study. ForePass produced profound improvements in insulin sensitivity and glucose regulation, with insulin sensitivity levels closely matching those previously observed following BPD surgery in humans and more than two-fold higher than in semaglutide-treated animals. During oral glucose tolerance testing, ForePass-treated animals demonstrated near-complete suppression of postprandial glucose excursions with substantially reduced insulin demand, consistent with restoration of insulin sensitivity.

“ForePass was designed around a central concept in metabolic disease biology that the upper intestine plays a major role in insulin resistance and glucose regulation," said Dr Giorgio Castagneto Gissey, Founder and CEO of Keyron. "These findings support the possibility that metabolic effects previously achievable only through highly invasive surgery may soon be achieved through a scalable, fully reversible endoscopic procedure that avoids lifelong drug dependency.”

Based on these findings, ForePass is advancing toward first-in-human clinical studies targeting severe obesity and metabolic disease.

The findings were reported in the paper, ‘Endoluminal device induces insulin sensitivity and greater weight control than semaglutide in pigs’, published in Gut. To access this paper, please click here (log-in maybe required)