Most weight loss interventions target obese or super-obese patients who have adjacent comorbidities, such as type 2 diabetes or sleep apnea. But Boston-based Gelesis aims to change that with its hydrogel pill Plenity, which was cleared by U.S. FDA in April. (See BioWorld MedTech, April 16, 2019.)
It presented a post-hoc analysis of pivotal trial data at Obesityweek – which took place Nov. 2 through 7 in Las Vegas – that showed the oral, nonsystemic, superabsorbent hydrogel pill enabled adults who reached a body mass index (BMI) of less than 27 to lose an average of 13.5% of their weight, with twice as many adults reaching that BMI with Plenity than on placebo. A BMI of about 25 to 30 is considered overweight, while higher than that is obese.
Plenity was cleared as an aid for weight management in overweight and obese adults with a BMI of 25-40 kg/m2, when used in conjunction with diet and exercise. About 80 million U.S. adults fall into the overweight category and have few options to aid them in weight loss, or to help them to prevent sliding into obesity and run the risk of the associated common comorbidities.
"It should give clinicians and patients more confidence that this can be used for people who are in the overweight category – and that's a BMI of 25 to 30. You don't have to be truly obese to benefit from Plenity," Gelesis CMO Harry Leider told BioWorld MedTech.
"This kind of safety and efficacy data for people who are at the lower end of the spectrum by the time they get to the end of the study has the implication that Plenity can be used with confidence in most people who want to lose 10 to 15, or [even] 20 to 25 pounds," he added. "They don't necessarily have to be in that obese category."
The company expects to expand upon this early launch next year. A full-capacity, unconstrained launch will kick into gear in 2021. The price point is expected to be low enough that motivated patients will be willing to pay for it out of pocket; U.S. payers have a mixed history of paying for weight loss drugs.
In Europe, Gelesis already has submitted for a CE mark and is optimistic that it will receive it within the next few months. The company likely will partner in Europe for distribution. In China, India and the Middle East, Gelesis has attracted licensing interest and plans to do deals on that front.
All told, about 150 million U.S. adults are overweight or obese. But the health consequences weigh heavily on those who are simply overweight; roughly 40% of BMI-related deaths were in overweight adults.
"In order to break the cycle of adult obesity and have a meaningful impact on both individual and population health, we should shift the treatment paradigm to prevent obesity by treating patients when they are overweight and before they meet the clinical definition of obesity," said Ken Fujioka, a weight loss expert and endocrinology researcher at Scripps Clinic and scientific advisor to Gelesis. "This subgroup analysis provides clear and compelling insight into the safety and efficacy of Plenity treatment in overweight patients with a lower BMI, and – in conjunction with the exciting results from the overall study – provide a strong rationale for Plenity as an early therapeutic intervention for adults with excess weight."
The overall study, known as Gelesis Loss Of Weight (GLOW), enrolled 436 patients with a BMI of greater than 27 and less than 40. The six-month study involved a 2.25 g dose of Plenity twice daily. Active and placebo arms both included a low-calorie diet and prescribed daily physical activity.
In previously reported co-primary endpoint data, 59% of adults in the treatment group achieved weight loss of 5% or more, thereby meeting that primary endpoint. But on the second primary endpoint, Plenity did not achieve 3% superiority for placebo-adjusted weight loss. It did achieve superiority, but not at the prescribed rate, with a result of 6.4% loss vs. 4.4% for placebo.
Still, Plenity offered twice the odds of achieving weight loss of greater than 5% as compared with placebo. And 26% of adults were super-responders, with more than 10% of weight lost. On average, they lost 14% of their weight, or about 30 pounds.
Gelesis also has started a clinical trial for its second candidate, still known as Gelesis 200. It also is based on hydrogel, but this time a slightly firmer version. It's slated to report data in 2020 and will aim to achieve weight loss and improved glycemic control in type 2 diabetes patients and those with prediabetes.
As part of that study, there is a smaller sub-study aimed at better elucidating the mechanisms of action. Plenity works, at least in part, by expanding and offering a feeling of fullness with water in the stomach. But the company also wants to understand how it affects gut hormones, such as GLP-1, and the gut microbiome. Gelesis suspects that it may offer positive effects on hormones in the small intestine and the microbiome.
Gelesis also is working on another version of its hydrogel for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, which are indications that are associated with obesity and also common among patients with type 2 diabetes.
Leider noted that the data attracted substantial attention at the Obesityweek meeting. "There's a tremendous amount of excitement. As soon as people hear about it, the very first question we always get is: 'When can I get it?'
"There's just a lot of enthusiasm, and this is really a mechanistic breakthrough, unlike anything this provider community has ever seen," he concluded. "They're looking for new solutions, especially ones that are well-tolerated and safe. And a lot of the specialists here have raised the issue of maybe even using Plenity in combination with other therapies, which we didn't do in our clinical trial. But these experts are really looking for new tools, new approaches, new things to try with their patients."