Innovative approaches to weight loss have fallen flat in recent decades, even as almost 40% of U.S. adults are obese and an additional 30% are overweight. Startup Gelesis Inc. has gained an FDA clearance for the first prescription weight loss treatment in years, a hydrogel pill known as Plenity (formerly Gelesis100).

It's indicated for people who are overweight or moderately obese with a body mass index (BMI) of 25-40 kg/m2, in conjunction with diet and exercise. The oral pill is regulated as a medical device because it works mechanistically by filling the stomach, rather than aiming to trigger a brain pathway to reduce appetite as weight loss drugs typically do.

Consumer telemedicine?

"While we are regulated by the FDA as a medical device, Plenity is prescribed and taken by patients like a drug," explained Gelesis Chief Medical Officer Harry Leider to BioWorld. Leider noted that devices typically are prescribed for patients who are at the higher-end BMI risk range from a health standpoint. "Plenity is more geared towards patients who are overweight or with mild to moderate levels of obesity because of its efficacy and safety profile, compared with other options."

The Boston-based company plans to start a targeted launch of Plenity during the fourth quarter of this year. It will monitor clinical experiences and use that to shape a full launch during the second half of 2020. Gelesis also has submitted for a CE mark, which it expects a response on later this year.

It plans to price Plenity within consumer reach without reimbursement, but it has not yet disclosed the price. Gelesis also aims to connect consumers with physicians via telemedicine systems for Plenity prescriptions, as it is relatively straightforward to assess patient eligibility for the low-risk weight-loss approach. It is currently in conversations with telemedicine providers.

"The majority of physicians tend to prescribe when it's later in the course in terms of the natural history for someone who is gaining weight progressively. So we believe that activating the consumer is very important," said David Pass, Gelesis' chief operating officer and head of commercial. "We're going to leverage . . . telemedicine – specifically the movement you have to help patients create an easy, frictionless experience with a health care professional.

"At the same time, we want to make sure that the appropriate level of interaction occurs between the health care professional and the patient; we're working through that as we go forward," he added. "We're also looking at home delivery of the product by mail order, as well as a packaging that fits into their lifestyle. So, the idea would be potentially to make physicians available via telemedicine, who would then prescribe it directly to the patient."

How it works

The capsules are composed of tiny beads made of cellulose cross-linked with citric acid. When hydrated, they create a hydrogel matrix that expands in the stomach and mixes with food that has been eaten. With roughly the consistency of chewed vegetables, this is not a solid mass. As it moves through the intestines, it is broken down and expelled in feces.

In a 436-subject pivotal trial, Plenity use over six months enabled 59% of adults in the indicated BMI range to lose more than 5% of their body weight. That exceeded the predefined co-primary endpoint of at least 35% of subjects losing more than 5% of their body weight. The study did not meet a second co-primary endpoint of placebo-adjusted weight loss with a superiority margin of 3%. Plenity improved upon placebo by 2%, rather than 3%.

In the study, 26% of subjects achieved weight loss of 10% in six months. Gelesis noted that nonresponders typically were patients who had less than 3% weight loss after eight weeks; that had an 80% sensitivity and specificity. That could be used to offer additional support or discontinue treatment for identified patients. The FDA label has no limit on length of use for Plenity.

"The scientific data supporting Plenity's positive effects on weight make it a powerful tool to help with weight management. The most compelling aspects of this approach are its effectiveness, novel mechanism of action and impressive safety data. This approach creates another arm in the treatment algorithm of weight management and could be used by an overwhelming majority of people struggling with weight issues," said Ken Fujioka, a weight loss expert, endocrinology researcher at Scripps Clinic and scientific advisor to Gelesis.

Future plans

In addition to Plenity, Gelesis has a pipeline of similar products that vary by elasticity and hydration characteristics. It has the ongoing LIGHT-UP study for Gelesis200 in type 2 diabetes and prediabetes patients; that study is slated to read out in 2020. It also has preclinical candidates in nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, mucositis/inflammatory bowel disease and chronic constipation.

Gelesis is the first Puretech Health company to make it from discovery to FDA clearance. With its clearance in hand for a massive potential market, Gelesis may prove ready for Wall Street. The startup has raised almost $120 million since its 2006 inception, according to U.S. SEC filings. It's in the midst of looking at raising more financing to back the launch – with both public and private options still on the table, making it a potential IPO candidate.

"This FDA clearance is a major milestone for the Gelesis team and our technology," summed up Gelesis founder and CEO Yishai Zohar. "With Plenity, Gelesis is introducing a completely new approach with a unique mechanism of action to aid in weight management, with efficacy and safety supported by positive data from large clinical studies."