Gelesis has claimed success in a pivotal trial of its obesity candidate. More than half of participants who took the swelling hydrogel particles lost weight, encouraging Gelesis to file for approval despite missing the other co-primary endpoint.
The six-month, 436-patient study tested the safety and efficacy of Gelesis100, a capsule filled with hydrogel particles. When swallowed with water before eating, the capsules release the particles in the stomach, where they hydrate and balloon in size. This is intended to reduce hunger. The particles release most of the water in the large intestine and shrink back to a size that enables them to be excreted.
Gelesis now has data suggesting this mechanism of action aids weight loss, although the study fell short of delivering a clean sweep of positive results.
Boston, Massachusetts-based Gelesis is focusing on the proportion of adults who lost 5% or more weight, a percentage it views as clinically meaningful. The trial found 58% of people in the Gelesis100 arm experienced such weight loss, compared to 42% in the placebo cohort. That resulted in a p value of 0.0028 and a statistically significant separation between the Gelesis100 and placebo groups.
Gelesis100 performed less impressively against the other co-primary endpoint. The device failed to achieve a mean placebo-adjusted weight loss of 3% or more, resulting in a miss against that key marker of efficacy. Gelesis is yet to say how the capsule performed against a clutch of secondary endpoints, although it did point to a 10% weight loss outcome not listed among the study’s predefined measures on ClinicalTrials.gov to argue for its efficacy. A spokesperson for Gelesis said the 10% measure was a predefined endpoint.
The next step is to find out what regulators make of the data. Gelesis hopes to file for approval based on the data but needs to run it by regulatory authorities to get their thoughts first. Peter Welford, an analyst at Jefferies, thinks the data support a filing, despite their shortcomings.
“Failing to meet both co-primary endpoints is not 'best' case, in our view, but given nearly 60% of adults achieved clinically meaningful 5+% weight loss and the clean safety profile, plus prior Flow trial data, we are optimistic regulatory authorities should support filings,” Welford wrote in a note to investors.
The Flow data referred to by Welford were generated in an earlier study, which provided Gelesis with a platform from which to raise $31.5 million for the pivotal trial but failed to impress everyone. Speaking in 2014, one endocrinologist called Flow’s two percentage point difference in weight loss between the treatment and control arms “very modest.”
Gelesis’ pitch to regulators and, if Gelesis100 gets that far, doctors is at least partly based on safety. The company’s claim the capsule is less invasive than devices or surgery and safer than drugs was backed up by the pivotal trial, which saw no serious adverse events and a lower dropout rate in the Gelesis100 arm than the placebo group. The FDA has previously indicated its views on the safety of Gelesis100 by classing the pivotal trial as a nonsignificant risk device study.