Results from the LIGHT-UP clinical trial for adults with overweight or obesity who have prediabetes or type 2 diabetes and were treated with either GS200 or placebo, revealed that approximately six out of ten adults treated with GS200 achieved clinically meaningful response to treatment (achieving at least 5% body weight loss), losing on average 11% of their body weight (~23lbs) and an average reduction of 5.5 inches off their waist circumference. The findings were presented at the European Congress on Obesity 2022.
GS200 is a non-systemic, superabsorbent hydrogel in development for the treatment of obesity and for glycemic control. It is made by utilizing the same proprietary hydrogel platform technology Gelesis developed for its previously FDA cleared product, GS100 (Plenity). Like GS100, GS200 is made from naturally derived cross-linked modified cellulose, however with a higher molecular weight.
GS200 was designed to hydrate faster and create a higher elastic response in the GI tract compared with GS100. Its properties were optimised in preclinical studies based on its effect on the gut barrier and microbiome, as well as reduced insulin resistance and weight loss. Like GS100, GS200 is a three-dimensional matrix of cellulose, capable of absorbing a much larger volume of water in the stomach and small intestines.
Orally administered in capsules with water before meals, GS200 particles rapidly absorb water in the stomach and homogenously mix with ingested food. This creates thousands of small individual gel pieces with composition (cellulose and water) and elasticity (firmness) similar to solid ingested raw vegetables, without any caloric value. Once it arrives in the large intestine, the hydrogel is partially broken down by naturally occurring enzymes, and loses its three-dimensional structure along with most of its absorption capacity.
The released water is reabsorbed in the large intestine, and the remaining cellulosic material is expelled naturally. GS200 is considered a medical device because it achieves its primary intended purpose through mechanical modes of action consistent with mechanobiology constructs, and it is not absorbed through the gastrointestinal tract. GS200 received a Non-Significant Risk (NSR) determination by the FDA for the LIGHT-UP study.
Participants in LIGHT-UP were also instructed to follow a modestly reduced calorie diet along with moderate-intensity physical activity. In the GS200 group there was clear and early separation between responders and non-responders to treatment, and response to therapy could be predicted as early as 6 weeks of treatment.
“There is a very large population of adults with prediabetes and diabetes who have a greater need for weight loss due to higher medical risks and a greater difficulty losing weight,” said Dr Frank L Greenway, Medical Director and Professor at the Pennington Biomedical Research Center of the Louisiana State University and one of the study’s lead investigators. “The compelling weight loss data that favours diabetes and prediabetes is unique among weight loss treatments. Its convenient oral administration, and very favourable tolerability make it a potentially important tool to aid clinicians and patients achieve clinically meaningful weight loss.”
The multicentre, double-blind, randomized, placebo-controlled study enrolled 254 subjects and was designed to assess the change in body weight in adults with overweight or obesity, who have prediabetes or diabetes, after six months of treatment with a new oral superabsorbent hydrogel (GS200) or placebo. The study met both of its primary endpoints: the proportion of participants who achieved at least 5% body weight loss and the change in body weight after six months of therapy.
A highly binary effect was observed with the GS200 treatment group, with a clear separation between responders and non-responders as early as after 6 weeks of treatment. Among the adults who completed the study protocol requirements (PP population), 64% of GS200-treated adults were Responders vs. 41% in the placebo group (p=0.001). In the analysis which also included data from the participants who didn’t fully complete the study (ITT-MI), 55% of GS200-treated adults were Responders vs. 34% in the placebo group (p=0.0004). The average body weight loss of the Responders was 11% (approximately 23 pounds) and their waist circumference was reduced by 5.5 inches on average.
Importantly, Gelesis treated individuals had 2.8 higher odds compared with placebo to become Responders (p=0.0004), achieving the first primary endpoint of the study.
With respect to average total weight loss, the complete GS200 treatment group (including both Responders and Non-Responders) demonstrated superiority over placebo after 6 months of treatment (body weight loss of 7.1% vs. 4.6%, P=0.0029 in the PP population or 6.9% vs. 4.3%, P=0.0011 in the ITT population), thereby achieving the second primary endpoint.
GS200 demonstrated a highly favorable safety and tolerability profile as the overall incidence of adverse events (AEs) in adults treated with GSP200 was similar to the incidence of AEs in the placebo group.
Approximately 1 out of 3 GS200-treated adults were “super responders,” losing at least 10% of their body weight and on average losing 13% (~30lbs) or 7 inches off their waist circumference.
“There is a real need for tolerable, effective, and affordable therapeutics to aid in weight loss for patients with prediabetes and type 2 diabetes. Approximately 130 million Americans have prediabetes or type 2 diabetes and approximately 80% struggle with excess weight. Importantly, these individuals also have a high risk of heart disease and other serious chronic conditions, related to overweight and obesity, making this one of the biggest public health issues facing our society,” said Harry L. Leider, MD, MBA, FACPE, Chief Medical Officer of Gelesis. “These data show that GS200 produces clinically meaningful weight loss for the majority of patients and that it’s possible to identify these responders early in treatment. Given the highly attractive safety and tolerability profile, GS200 has the potential to become an exciting new therapy, especially among those in the lower spectrum of excess weight who also have prediabetes or type 2 diabetes.”