November 3, 2014
Gelesis Presents Additional Clinical Data at the Obesity Society Annual Meeting
Gelesis100 demonstrated clinically relevant improvement in glycemic control in subjects at high risk for Type 2 Diabetes in a 12-week study, in addition to previously disclosed weight loss.
Boston, Massachusetts – November 3, 2014. Gelesis, a company focused on the development of novel therapies to induce weight loss and improve glycemic control in overweight and obese patients, announced today that it presented additional results from a proof of concept study of its lead product candidate, Gelesis100, at The Obesity Society Annual Meeting in Boston, MA. In the 12-week study (summarized in “About the FLOW Study” below), Gelesis100, taken twice daily, demonstrated clinically relevant improvement in fasting glucose, fasting insulin, insulin resistance, and fasting glucose status in pre-diabetic overweight and obese subjects. The company previously disclosed that Gelesis100 induced statistically significant weight loss in the same study, with a particularly dramatic effect in prediabetic subjects.
The FLOW study demonstrated conversion from prediabetic fasting glucose status at baseline to normal fasting glucose status at the end of treatment in 56% of subjects on Gelesis100 2.25 g, 78% of subjects on Gelesis100 3.75 g, and 27% of subjects on placebo. “Most of the prediabetic subjects who participated in the study’s two active treatment arms converted to normal fasting glucose status by the end of the 12-week treatment period. This suggests that Gelesis100 has the potential to prevent or delay the onset of type 2 diabetes in overweight and obese subjects,” said Professor Arne Astrup, MD, a lead study investigator, leading obesity expert, and Head of The Department of Nutrition, Exercise and Sports at the University of Copenhagen, Denmark.
Improvements in glycemic control parameters were observed in both weight responders (≥ 5% weight loss) and weight non-responders (< 5% weight loss), suggesting that both weight-dependent and weight-independent mechanisms are involved. “The improvement in glycemic control parameters with Gelesis100, independent of weight change, is of particular importance and interest for prediabetic subjects and clinicians.” said Hassan Heshmati, MD, Gelesis’ Chief Medical Officer. “We believe that Gelesis100 achieves this through several different mechanisms in the gastrointestinal tract, some of them not being directly involved in weight loss,” he added.
Fasting glucose changes, mean ± standard deviation (SD), from baseline to the end of treatment were -5.8 ± 9.9% (p = 0.003 vs placebo) in the Gelesis100 2.25 g arm, -3.3 ± 9.8% in the Gelesis100 3.75 g arm (p = 0.057 vs placebo), and 1.2 ± 11.1% in the placebo arm. Fasting insulin changes from baseline to the end of treatment were -7.6 ± 49.4% (p = 0.053), -14.1 ± 40.6% (p = 0.022 vs placebo), and 24.4 ± 92.2%, in the Gelesis100 2.25 g, Gelesis100 3.75 g, and placebo arms, respectively. HOMA-IR (insulin resistance) changes from baseline to the end of treatment were -12.1 ± 49.5% (p = 0.025 vs placebo) in the Gelesis100 2.25 g arm, -16.6 ± 44.1% (p = 0.016 vs placebo) in the Gelesis100 3.55 g arm, and 28.8 ± 104.1%, in the placebo arm.
Gelesis100 exhibited a safety profile that was similar to or better than placebo. No serious adverse events were observed in the active arms. The most common side effects were of gastrointestinal origin, usually of mild intensity, occurring at different times during the course of the study, and resolving within one week in most cases. No dropouts due to adverse events were observed in the Gelesis100 2.25 g arm.
“There are approximately 86 million prediabetic Americans who are at high risk of developing type 2 diabetes,” said Gelesis’ Founder and Chief Executive Officer, Yishai Zohar. ”The treatment strategy for these patients, who are often overweight or obese, relies on diet and exercise and, in some cases, pharmacotherapy. We believe that if future studies confirm the promising efficacy and safety profile observed in the FLOW study, including the previously disclosed weight loss results, Gelesis100 could become an important tool for the treatment of this population,” said Zohar.
About Gelesis and Gelesis100
Gelesis100 is a non-systemic, orally administered capsule designed to induce weight loss. Each capsule contains thousands of proprietary, biocompatible hydrogel particles synthesized with starting materials that have been designated as Generally Recognized As Safe (GRAS) by the U.S. Food and Drug Administration (FDA). Gelesis100 capsules are taken prior to a meal with water, after which the small particles within the capsules hydrate and expand in the stomach and small intestine, triggering several important satiety and glycemic control mechanisms. Gelesis100 has several built in safety features: a) the volume it creates is limited by the amount of water consumed, b) the hydrated particles which are ~2 mm in size, do not cluster or stick together and have similar elasticity (rigidity) as ingested food, and c) the particles partially degrade in the colon, releasing absorbed water.
Gelesis is a clinical stage company focused on the development of novel therapies to induce weight loss and improve glycemic control in overweight and obese patients. The Gelesis executive and advisory team includes some of the world's leading experts in obesity research and clinical development, entrepreneurs, and innovators in advanced materials. Gelesis was co-founded by PureTech, a science and technology commercialization company.
About the FLOW Study
First Loss Of Weight (FLOW) was a multicenter, double-blind, placebo-controlled, parallel-group, 12-week study, designed to explore the efficacy, safety, and tolerability of Gelesis100. The effect on body weight, fasting glucose, fasting insulin, insulin resistance, and fasting glucose status of chronic oral administration of Gelesis100 was assessed in 128 non-diabetic, overweight and obese subjects randomized to two Gelesis100 arms, 2.25 g (n = 43), 3.75 g (n = 42), and a placebo arm (n = 43). Subjects ingested capsules containing Gelesis100 or placebo with 500 mL of water (two glasses), twice daily, before both lunch and dinner and received counseling to reduce their diet by < kcal/day below their daily requirements.
One hundred twenty-two normal or prediabetic subjects had at least one post-baseline glycemic control parameter assessment in the intention-to-treat (ITT) population. The ITT population (125 subjects who had at least one post-baseline body weight assessment, 40 males, 85 females) had a mean age ± SD of 44 ± 12 years and a mean body mass index ± SD of 31.7 ± 2.4.
The weight loss results of the FLOW study were previously presented at the joint meeting of the International Congress of Endocrinology and The Endocrine Society: ICE/ENDO 2014 on June 23, 2014 in Chicago. In the ITT population, the body weight changes from baseline to the end of treatment were -6.1 ± 5.1% (p = 0.026 vs placebo), -4.5 ± 4.5%, and -4.1 ± 4.4%, in the Gelesis100 2.25 g, Gelesis100 3.75 g, and placebo arms, respectively. Subjects receiving 2.25 g of Gelesis100 who had elevated fasting blood glucose before treatment (> median of 93 mg/dL) had greater weight loss, losing 8.2 ± 5.3% (3.8% placebo adjusted; p = 0.006) of their body weight. The greatest weight loss occurred in prediabetic subjects whose starting fasting blood glucose level was 100 to < 126 mg/dL. These subjects lost an average of 10.9 ± 4.3% (5.3% placebo adjusted; p = 0.019) of their body weight in 12 weeks. There was a significant correlation between fasting glucose at baseline and change in body weight in Gelesis100 2.25 g arm (r = -0.50; p < 0.001).
About Overweight and Obesity
Obesity is a serious medical condition that is rapidly growing in prevalence worldwide. According to a 2012 Centers for Disease Control (CDC) report, approximately 79 million Americans were obese. In addition, approximately 77 million Americans were overweight, with many expected to cross the threshold into obesity in the near future. Obesity significantly increases the lifetime likelihood that an individual will have additional complications such as type 2 diabetes, heart disease, osteoarthritis, and certain types of cancer.
About Prediabetes and Type 2 Diabetes
Type 2 diabetes is a chronic condition whereby the body resists the effect of insulin or does not produce enough insulin to maintain a normal glucose level. According to the American Diabetes Association (ADA), diabetes was the fastest growing disease and the seventh leading cause of death by disease in the United States in 2010. In 2012, approximately 29 million Americans suffered from type 2 diabetes, of whom greater than 85% were overweight or obese. An additional 86 million American adults over the age of 20 were considered prediabetic (defined by a fasting blood glucose level ≥ 100 mg/dL and < 126 mg/dL), with approximately 1.7 million new diagnoses of type 2 diabetes per year.