Unique Weight Management Rx Cleared by FDA

A simple but unique way to lose weight without stimulation, which could become the first treatment option for overweight patients with prediabetes.

Gelesis announced that the Food and Drug Administration (FDA) has cleared Plenity (Gelesis100) to aid in weight management for overweight and obese adults, in conjunction with diet and exercise.

There is an urgent need for therapies that increase patients’ odds for achieving clinically meaningful weight loss with little or no additional safety risk compared with lifestyle interventions. Such therapies could allow clinicians to intervene earlier in the overweight and obesity continuum and prevent progression or delay associated comorbidities while helping to overcome the current therapeutic inertia.

Available in capsule form, Plenity, a non-systemic, superabsorbent hydrogel, is intended for use in adults with a body mass index (BMI) of 25–40kg/m2 and is taken orally before lunch and dinner. It is the first prescription product to be approved for use in adults with a BMI as low as 25kg/m2, with or without comorbidities such as hypertension, type 2 diabetes, or dyslipidemia.

The capsules consist of a 3-D hydrogel matrix made by cross-linking cellulose and citric acid. Once ingested, the capsules release non-aggregating particles that absorb water in the stomach, creating individual gel pieces with the elasticity of plant-based foods but without the calories. The gel pieces expand and mix with the contents in the stomach and small intestine, making the patient feel fuller. The particles pass through the digestive system, break down in the colon, and are eliminated with a bowel movement.

Plenity and its prototypes were evaluated in 5 clinical studies where it consistently showed efficacy and favorable safety and tolerability profiles. In the GLOW (Gelesis Loss of Weight) study (N=436), adults with overweight or obesity were evaluated for change in body weight after 6 months of treatment.

Notably, significantly more patients treated with Gelesis100 achieved ≥ 5% weight loss (co‐primary end point) versus placebo (59% vs. 42%), and 27% of patients treated with Gelesis100 achieved ≥ 10% weight loss versus 15% of patients treated with placebo. Patients treated with Gelesis100 had twice the odds of achieving ≥ 5% weight loss versus placebo. For these responders, the mean weight loss was 10.2% ± 4.1%. Similarly, Gelesis100‐treated patients had twice the odds of achieving ≥ 7.5% and ≥ 10% weight loss. Patients treated with Gelesis100 sustained markedly greater weight loss over time without plateauing.

In addition, the proportion of adults who were super-responders (defined as ≥10% weight loss) was higher in the Plenity intent-to-treat population vs the placebo group (27% vs 15%); super-responders achieved about 14% weight loss (~30lbs). Moreover, patients who received Plenity were twice as likely to achieve ≥5% and ≥10% weight loss vs placebo.

The Gelesis Loss Of Weight (GLOW) study was a 24‐week, multicenter, randomized, double‐blind, placebo‐controlled study in patients with BMI ≥  27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co‐primary endpoints were placebo‐adjusted weight loss and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss.

Gelesis100 treatment caused greater weight loss over placebo achieving 2.1% superiority but not 3% super‐superiority. Importantly, 59% of Gelesis100‐treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100‐treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug‐naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks.

Gastrointestinal disorders, infections/infestations, and musculoskeletal/connective tissue disorders were the most common treatment-related adverse events.

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.

From the results it was concluded that, Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.

Practice Pearls

• Plenity found to improve blood pressure, hyperlipidemia and fasting blood glucose,
• 59% of Plenity-treated adults achieved ≥5% weight loss and 27% achieved ≥ 10% versus 42% and 15% in the placebo group,
• Gelesis100 received a Nonsignificant Risk designation by the Food and Drug Administration.

Obesity: Volume27, Issue2  February 2019 Pages 205-216