A post-hoc analysis showed that treatment for weight management with Plenity decreased a marker for liver fibrosis (the NAFLD fibrosis score, or NFS) compared to placebo. This retrospective analysis of Gelesis’ GLOW (Gelesis Loss of Weight) pivotal study assessed the impact of oral superabsorbent hydrogel (OSH) treatment on liver health as measured by the NFS, which is intended to predict the presence of significant fibrosis using common clinical and laboratory values, including age, BMI, diabetes status, AST/ALT ratio, platelet count and serum albumin.
Plenity is a non-systemic oral superabsorbent hydrogel that is FDA-cleared to aid in weight management in adults with excess weight or obesity, Body Mass Index (BMI) of 25 to 40 kg/m², when used in conjunction with diet and exercise.
Gelesis’ portfolio of non-caloric superabsorbent hydrogels are conveniently administered in capsules taken with water to create a much larger volume of small, non-aggregating hydrogel pieces that become an integrated part of the meals, and act locally in the digestive system. The capsules are taken 20-30 minutes before lunch and dinner with 16 oz of water, acting locally in the GI tract to make you feel fuller. Using a novel biomimetic approach, its structure and properties were inspired by vegetables. Plenity is available now in a limited release, with broad commercial availability later in 2021.
In the analysis, NFS was calculated at baseline and at six months for 317 study participants who had all available data at both timepoints. At baseline, 53.6% of patients receiving Plenity and 53.7% receiving placebo had a moderate or high NFS. At six months, fewer patients had moderate or high NFS in the Plenity group (45.2), while there was no change in the placebo group. The absolute numerical change in score was compared between baseline and six months, and a statistically significant reduction was observed in NFS within the Plenity group (p=0.030), but not the placebo group (p=0.824). The difference between groups was statistically significant (p=0.043).
“These data further emphasise the need to address pre-obesity with and without comorbidities. Liver health is not always considered with a weight management plan, and yet early intervention may help prevent patients from developing metabolic-related liver disease,” said study author, Dr Christopher Still, Medical Director for the Center for Nutrition and Weight Management, and Director for Geisinger Obesity Research Institute at Geisinger Medical Center. Still also participated in the GLOW study.
The Gelesis Loss Of Weight (GLOW) Study was a randomized, double-blind, placebo-controlled, parallel-group study enrolling 436 adults with a body mass index (BMI) ≥ 27 and ≤ 40 kg/m2, including those with prediabetes or type 2 diabetes. The six-month study compared a 2.25g dose of Plenity, administered twice daily, to placebo and was conducted at 33 sites across the US and several European countries. Both the active and placebo arms also included a reduced calorie diet and daily physical activity.
The study had two predefined co-primary endpoints: at least 35% of patients taking Plenity achieving ≥ 5% weight loss (categorical endpoint) and placebo-adjusted weight loss with a super-superiority margin of 3%. In addition, a prespecified analysis of simple superiority was also performed. The study met and exceeded the predefined categorical endpoint, with 59% of adults in the treatment group achieving weight loss of 5% or greater. The study did not meet the 3% super-superiority endpoint but demonstrated superiority of the Plenity treatment over the placebo group (–6.4% vs. –4.4%, p=0.0007). Plenity-treated individuals had twice the odds of achieving at least 5% weight loss vs. placebo (p=0.0008). In addition, 26% of the adults who completed the treatment with Plenity were “super-responders,” defined as achieving at least 10% weight loss. These super-responders achieved an average of about 14% weight loss or approximately 30 pounds.
The overall incidence of adverse events (AEs) in the Plenity treatment group was no different from placebo. The most common treatment-related adverse events (TRAEs) were gastrointestinal disorders (158 TRAEs in 84 [38%] subjects in the Plenity arm, compared to 105 events in 58 [28%] subjects receiving placebo), infections and infestations (2 events in 2 [1%] subjects with Plenity and 1 events in 1 [1%] subjects with placebo), and musculoskeletal and connective tissue disorders (3 events in 2 [1%] subjects with Plenity and 0 in 0 [0%] subjects with placebo). There were no serious adverse events (SAE) in the Plenity treatment group, whereas there was one (1) SAE in the placebo treatment group.
The data support further trials of OSH treatment for metabolic-related liver diseases. Gelesis’ plans to enrol the first patient in a clinical study of its OSH GS300 in non-alcoholic steatohepatitis and non-alcoholic fatty liver disease, or NASH/NAFLD, by the end of 2021.