Emerging Non-Surgical Gastric Devices Gain Approval for Weight Management

With Richard I Rothstein, MD, and J. Michael Gonzalez-Campoy, MD, PhD

FDA Approves TransPyloric Shuttle Nonsurgical Device for Obesity

The Food and Drug Administration (FDA) approved the TransPyloric Shuttle (TPS), an intragastric device that when implanted endoscopically was shown to be safe and effective in promoting significant weight reduction in individuals with obesity,¹˒² according to BAROnova, the device manufacturer.

Gaining regulatory clearance to market the shuttle and TPS delivery device was supported by results of a nine site, pivotal 2:1 randomized trial.³ The ENDObesity II study—a double-blind, sham-controlled trial—enrolled 302 patients, median age: 43 years (age range 22 to 60 years) with a diagnosis of obesity as determined by body mass index (BMI between 30-40 kg/m²) who were followed for one year.³

“The patients in the treatment group achieved a 9.5% weight loss as compared with 2.8% in the sham group,” said principal investigator, Richard I. Rothstein, MD, the Joseph M. Huber Professor and chair of the Department of Medicine at the Geisel School of Medicine at Dartmouth, in Lebanon, New Hampshire. “This 6.7% difference exceeded our aim of a minimum 5% weight loss outcome over the sham treatment.”

This pivotal study evolved from the first-in-man Australian ENDObesity I study that followed 20 patients for six months.4 “We observed that these individuals had not yet plateaued their weight loss as many were still losing weight when the device was removed, so our trial was designed to look at patients’ experience using the device for twice as long,” Dr. Rothstein said.

To enroll in this trial, patients had to have previously participated in a medically supervised or commercially acceptable medical nutrition weight loss program. All participants had made an attempt to lose weight as a prerequisite to joining the study.

“The make up of this cohort was 93% female; 72% Caucasian, 18% African American, 7% Latino, 1% each Asian, Native American and Native Hawaiian/Pacific Islander.3 In addition to the primary endpoint of total body weight loss, we monitored for key secondary outcomes including changes in blood pressure, quality of life, and lipids. Interestingly, only 6% of those enrolled had diabetes so we can’t say much about their outcomes from this trial,” Dr. Rothstein said.

“The TPS is inserted endoscopically and assembled in the stomach, where it moves into position across the pyloric outlet and intermittently blocks the free flow of food into the intestine; the aim is to provide a non-surgical weight loss option to patients. This gastric device helps individuals to feel full sooner and longer,” said Dr. Rothstein.

There are currently four first-generation intragastric devices approved for use: two water filled balloons (Orbera and Reshape), one gas filled balloon (Obalon) and an aspiration device (Aspire Assist). The TPS differs from inflatable intragastric balloons in that it is made of silicone and is substantially smaller and lighter than the water-filled gastric balloon devices, obviating some of the discomfort experienced in patients who have the bulkier devices.

For the trial,2 the TPS was left in place a full 12 months, which gave patients, who also received minimal lifestyle counseling, longer to adopt new, healthier eating habits—learning from the experience of discomfort that occurred when they ate too much when the device was in place, Dr. Rothstein said.

Patients who had the TPS device implanted for the year, lost 9.5% of their initial weight, in comparison to the sham-treated control group who lost only 2.8% of their initial weight (P < 0.001). Of patients who underwent the TPS procedure, 67% lost at least 5% of their initial weight (compared to 29.3% with sham; P < 0.001).3

More significantly, 39.5% of people treated with TPS lost at least 10% or more weight (compared to 14% with sham; P = .0001). Secondary outcomes including blood pressure and other cardiometabolic risk factors, as well as quality of life parameters, were improved in patients in the device group compared with sham.3

Only 2.8% of patients experienced serious adverse events (one patient each with esophageal rupture, upper abdominal pain, gastric ulcer, vomiting, and gastric obstruction), which all resolved without sequelae.

“About 20% of participants exited the study before completion, which is in sync with findings from other device studies,” said Dr. Rothstein. “The most likely reasons for patients to drop out included loss of interest, the follow-up commitment being too long, side effects including GI distress, which for some ensued from intentionally overeating, which led to nausea and vomiting.”

Responses from all participating sites were favorable for patient outcomes, such that all investigators look forward to adding the use of the TPS in our clinical practices," said Dr. Rothstein, who served as the lead investigator of the ENDObesity II study.2

“In an initial look at our data, it seems that those patients who lose weight during the first three months seem most successful at weight loss at one year,” Dr. Rothstein said, “so that even at one month or so, clinicians will have an early predictive indicator of its efficacy in an individual, similar to that of bariatric surgery.5

Regarding the possibility of extending use of the TPS beyond one year, Dr. Rothstein said: “the device should be able to stay in place longer— perhaps up to two full years—given that adverse events were uncommon and optimal device dwell time is not known. Asymptomatic ulcers seen in some patients did not cause any major adverse events.3

Of the growing prevalence of obesity in the US, we should be asking—what can we do? Certainly, providing non-invasive options such as devices that can be done endoscopically to mimic bariatric surgical procedures, said Dr. Rothstein. Intragastric devices such as the TPS may be beneficial in certain populations such as teenagers for whom a reversible method of weight loss is preferable as well as those opposed to surgery or in which diet and lifestyle and pharmacotherapy hasn’t proven ineffective.

“For the right patient, the TPS will be most effective as a weight loss option when patients adhere to smaller portion sizes, avoid overeating, and follow the nutrition advise provided,” he said.

“We see significant advantages in the use of endoscopic procedures for weight loss, which can mimic the mechanisms and physiologic effects of bariatric surgical procedures but are non-invasive and reversible,” Dr. Rothstein said. “Consider that only ~6% of those who are obese receive treatment of their condition, with only 1% of those eligible for a gastric bypass procedure receiving it, representing a major, as yet, unmet need for ~94% of individuals with obesity .”

Since the durability of weight loss was not addressed by the ENDObesity II trial,

the Dartmouth investigators have continued to follow the patients in their clinic, which had the largest number of patients enrolled, according to Dr. Rothstein, and most completed the one year post-trial follow-up. “We intend to share the results in the near future with the hope of beginning to shed light on the prospect of weight maintenance after use of the TPS device.

“Since we are beginning to see chronic diseases—namely, back and joint pain, cardiovascular disease, diabetes—developing sooner in younger adults rather than at 55-60 years, we should consider expanding the use of TPS type devices particularly in adolescents in order to prevent obesity-related comorbidities from manifesting at 25-35 years old, he said. Although not yet studied in adolescents, that may be an important target group for early less invasive intervention.

According to the company,1,2 "the TransPyloric Shuttle/TransPyloric Shuttle delivery device is used in obese adult patients with a BMI of 35.0-40.0 kg/m2 or a BMI of 30.0 to 34.9 kg/m2 with an associated medical condition (for example, diabetes) who have been unable to lose weight [with a] diet and behavior modification program, and exercise. It is intended to be used while a patient participates in a diet and exercise plan supervised by a healthcare provider."

“At present, typically none of the FDA-approved intragastric devices are reimbursed through health insurance; It is mainly a self-pay model much the same as cosmetic surgery procedures,” said Dr. Rothstein. “These devices need to be covered to assure wider access and adoption in order for us to see a real impact—to avoid the development of unfortunate comorbidities that are associated with obesity such as type 2 diabetes, heart disease, stroke, and some cancers.”

When asked about the timing of a product launch, there was no response from the company regarding their plans to bring the TPS to market.

Gelesis Granted FDA Clearance to Market PLENITY for Weight Loss

Gelesis, a biotechnology company developing first-in-class oral, non-systemic, superabsorbent hydrogel device cleared to treat obesity and other chronic diseases related to the gastrointestinal (GI) tract, received FDA clearance for PLENITY (Gelesis100), to aid in weight management in adults with overweight or obesity (body mass index (BMI) of 25–40 kg/m²) when used along side nutrition and lifestyle behavioral efforts.³

PLENITY—taken in capsule form with water before lunch and dinner— is made by cross-linking cellulose and citric acid to form a three-dimensional hydrogel matrix. This new prescription-only option has no limitation on the length of its use for weight management.

“This FDA clearance is a major milestone for the Gelesis team and our technology, and we are thrilled to be able to bring this new prescription product to the millions of people looking for a safe, validated and convenient treatment option to manage their weight without surgery or stimulants,” said Yishai Zohar, founder and chief executive officer of Gelesis. “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.”³

PLENTIY works by releases thousands of non-aggregating particles that when combined with water in the stomach creating small gel particles with firmness similar in consistency to vegetables but with no caloric value.⁴ These particles increase in volume in the stomach and small intestine promoting a feeling of fullness that promises to achieve weight loss.

In the multicenter, double-blinded, placebo-controlled pivotal trial— Gelesis Loss Of Weight (GLOW)—was initiated to assess for a change in body weight among 436 adults with overweight or obesity (BMI ≥ 27 and ≤ 40 kg/m2) after six months of treatment with PLENITY.⁴

The study had two primary endpoints: at least 35% of patients achieving ≥ 5% weight loss and placebo-adjusted weight loss with a super-superiority margin of 3%. In addition, a prespecified analysis of simple superiority was also performed.

The investigators confirmed that the Gelesis100 device exceeded the primary outcome with 59% of adults in the treatment group achieving weight loss of at least 5%. As previously announced, the study did not meet the 3% super-superiority endpoint but demonstrated superiority of the PLENITY treatment over the placebo group (–6.4% vs. –4.4%, P = 0.0007). PLENITY-treated individuals had twice the odds of achieving at least 5% weight loss vs. placebo (adjusted odds ratio [OR]: 2.0, P = 0.0008).⁴

In addition, 26% of the adults who completed the 6-month study proved to be super-responders, having achieved an average of about 14% weight loss, which was around 30 pounds.⁴

The overall incidence of adverse events (AEs) in the treatment group was similar to placebo. The most common treatment-related adverse events were gastrointestinal disorders (38% in the treatment group vs 28% for placebo), infections (1% across both groups), and musculoskeletal and connective tissue disorders (1% in the treatment group 0 for those getting placebo).

Overall, this nonstimulant, nonsystemic weight management treatment has been shown in clinical studies to be effective, safe and well-tolerated.⁴

Gelesis plans to initiate a targeted US launch of PLENITY in the second half of 2019 and anticipates PLENITY will be broadly available by prescription in 2020.

A Weight Management Expert Applauds New Products

“There are two general approaches to achieve weight loss with bariatric procedures. one is to restrict the volume of the gut, thereby limiting food intake; and another method is to cause malabsorption of nutrients,” said J. Michael Gonzalez-Campoy, MD, PhD, Medical Director and Chief Executive Officer of the Minnesota Center for Obesity, Metabolism and Endocrinology in Eagan, Minnesota.

“These restrictive procedures have become less invasive over time, and currently include the only nonsurgical intervention for weight loss, the SmartByte device that restricts oral cavity volume and was granted clearance for marketing in April 2017,” said Dr. Gonzalez-Campoy.

“Both the TPS/TransPyloric shuttle delivery device, which is the fourth balloon system for intragastric use, and the Gelesis100 superabsorbent hydrogel, which comes in capsules but considered a medical device by the FDA because the material expands in the stomach, will provide viable choices for weight management by restricting gastric volume,” he said.

“Of the two, the Gelesis100 does not require an upper endoscopy for deployment, making it more readily accessible,” he said. “However, both have good clinical trial data to support their use as adjuncts to medical nutrition therapy, physical activity, and pharmacotherapy in the treatment of overweight, obesity, and adiposopathy.”

Dr. Rothstein had no financial conflicts to disclose other than that the study was funded by BAROnova nor did Dr. Gonzalez-Campoy.