Investigational candidate developed by Gelesis demonstrated significant 16 hour reduction in colonic transit time in patients with chronic idiopathic constipation
Gelesis has announced the presentation of data from a clinical study demonstrating that GS500 prototype (GS500/CSP01) provided a significant reduction in colonic transit time (CTT) in patients with chronic idiopathic constipation (CIC) relative to placebo. The data were presented at Digestive Disease Week 2019, held in San Diego, CA.
“One out of seven adults throughout the world suffer from chronic idiopathic constipation. This condition can have a significant negative impact on quality of life,” said Dr Braden Kuo, Gastrointestinal Unit in the Massachusetts General Hospital (MGH) Department of Medicine. “The safety and efficacy results of this study are intriguing and suggest further clinical evaluation in this very common, treatment resistant condition would be both warranted and welcome.”
Gelesis’ proprietary hydrogel product candidates are orally administered and synthesised from two naturally derived building blocks – modified cellulose cross-linked with citric acid – that create a three- dimensional matrix designed to achieve specific mechanical properties (high elastic response) through the gastrointestinal system. In order to assess the potential therapeutic benefits of the hydrogel’s specific mechanical properties, modified cellulose, the main building block of GS500, was included as an active control. This modified cellulose is a widely used soluble dietary fibre but lacks the three-dimensional structure of the superabsorbent hydrogel, and therefore creates significantly lower elastic response.
“The wireless motility capsule monitoring system allowed us to demonstrate that the superabsorbent hydrogel, in contrast to modified cellulose alone or placebo, accelerated colonic transit time,” said Dr Kyle Staller, Center for Neurointestinal Health and Division of Gastroenterology at Harvard-affiliated Massachusetts General Hospital. “This finding suggests that the three-dimensional structure of Gelesis’ hydrogel technology and specific elastic response may have contributed to the observed improvements in colonic transit time over the active fibre control in this study.”
The primary endpoint of this randomised, double-blind study was the change in CTT from pre-treatment to post-treatment as measured by wireless motility capsules. The test involves swallowing a small data recording device which transmits information to a wireless data receiver.
Two populations were evaluated separately, 27 subjects with CIC and 13 subjects with irritable bowel syndrome with constipation (IBS-C). Patients were randomised into three treatment groups to receive 21 days of treatment with either GS500 (n=20), active control (modified cellulose, n=11) or placebo (n=9). Each subject’s CTT was measured during the third week of treatment and compared to their baseline, collected during seven days of pre-treatment. Secondary outcome measures included improvement of relevant gastrointestinal (GI) symptoms.
In the CIC population on treatment, colonic transit time was reduced by approximately 16 hours (~31%) compared to baseline (p=0.02 compared to placebo). No statistically significant change was observed in the placebo or the active control groups. No improvement was observed in the IBS-C population, as well as no change in the reported GI symptoms which were the secondary endpoints. Two randomised patients did not complete the study, one in the treatment group due to a GI related AE, and one in the placebo group due to a faulty monitoring device. No serious adverse events were reported.
This pilot study of 40 subjects was powered to detect improvement in CTT (the primary endpoint). Recent data suggest that colonic transit time influences gut health and a longer faecal retention time is associated with CIC symptoms and less microbiome diversity. Further studies are required to assess the effect of Gelesis’ hydrogel technology on symptom improvement.
Gelesis is developing a novel hydrogel platform technology to treat overweight and obesity and chronic diseases related to the GI pathway. Gelesis’ proprietary approach is designed to act mechanically in the GI pathway to potentially alter the course of chronic diseases. In April 2019, Gelesis received FDA clearance for its lead product candidate, PLENITYTM. Gelesis is preparing to initiate a targeted U.S. launch of PLENITY in the second half of 2019 and anticipates PLENITY will be broadly available by prescription in the U.S. in 2020.
Additionally, Gelesis is developing its second candidate, Gelesis200, a hydrogel optimized for weight loss and glycemic control in patients with type 2 diabetes and prediabetes. Novel hydrogel mechanotherapeutics based on the Gelesis platform technology are also being advanced through a pipeline (GS300, GS400, GS500) in other GI inflammatory conditions where gut barrier and gut permeability potentially play a role, such as non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease (IBD). Recent preclinical data presented this year support the potential role of this novel hydrogel platform technology in restoring gut barrier function and intestinal tissue health.