Fractyl Health gets US FDA IDE approval for Revita Remain-1 study of weight maintenance in obesity after discontinuation of GLP-1 based drugs

Burlington, MassachusettsTuesday, April 2, 2024, 18:00 Hrs  [IST]

Fractyl Health, Inc., a metabolic therapeutics company focused on pioneering new approaches for the treatment of obesity and type 2 diabetes (T2D), announced US Food and Drug Administration (FDA) approval of a pivotal Investigational Device Exemption (IDE) to study Revita’s efficacy in maintaining weight loss following the discontinuation of GLP-1 receptor agonist (GLP-1RA) drug therapy, addressing a key unmet need in the treatment of obesity.

Obesity affects over 40% of the US population and is a critical precursor to various highly morbid and expensive chronic conditions such as type 2 diabetes, metabolic dysfunction-associated fatty liver disease, and cardiovascular disease.

The IDE approval launches the groundbreaking Remain-1 study, set to begin in the second half of 2024. Remain-1 is a randomized, double-blind trial of Revita versus sham in patients who have lost at least 15% total body weight on tirzepatide therapy. It is designed to be a pivotal study to potentially enable registrational filing for Revita for weight maintenance after GLP-1RA discontinuation. In parallel with the randomized portion of the Remain-1 study, Fractyl Health also announces Reveal-1, an open-label cohort that will follow a similar patient population and management protocol with anticipated open-label data updates as the study progresses.

The rationale for the Remain-1 pivotal study is based on a new need for therapeutic solutions that can offer durable weight maintenance without ongoing medical therapy. Highly potent drugs in the GLP-1RA class, including semaglutide (Wegovy) and tirzepatide (Zepbound), are now approved for the management of obesity and have dramatically altered the treatment landscape. However, real world studies report high discontinuation rates and clinical trials have indicated the risk of substantial weight rebound after discontinuation in many participants. Strategies to maintain weight loss independent of ongoing medical therapy could provide substantial clinical and economic benefits by extending the value of GLP-1RA drugs even after these medicines are discontinued.

“The unmet need in obesity is shifting from ‘How do we help people lose weight?’ to ‘How do we help people keep the weight off?’” said Christopher Thompson, MD MSc, director of endoscopy at Brigham and Women’s Hospital, co-director, Center for Weight Management and Wellness at Brigham Health, and Professor of Medicine at Harvard Medical School. “We now need new therapeutic strategies that can offer durable weight maintenance, and I am excited for the prospect of the Remain-1 pivotal study to hopefully address this massive challenge in obesity today.”

Revita is an outpatient endoscopic procedure that targets the duodenum and is designed to reverse pathology in the duodenal lining that is a root cause of obesity and T2D. In prior clinical studies of Revita conducted in people with T2D in the US and EU, pooled analyses of weight data provided evidence to support the potential for durable weight maintenance after a single Revita procedure.

The patient population for Remain-1 will consist of obese individuals with a BMI = 30 kg/m^2. These GLP-1RA-naïve individuals will initiate tirzepatide therapy, titrated to achieve at least a 15% total body weight loss, followed by discontinuation of tirzepatide and randomization to either Revita treatment or a sham procedure. At least 315 subjects will be randomized 2:1 to Revita or sham.

The primary objectives of the study are to demonstrate that Revita is superior to sham in percent change in body weight from baseline to week 24, and to demonstrate that a majority of Revita participants maintain clinically significant weight loss after discontinuing tirzepatide therapy.

"We believe there is substantial clinical and economic value in new approaches to obesity that can enable durable weight maintenance after stopping GLP-1 based drugs," said Dr. Harith Rajagopalan, CEO of Fractyl Health. "We were very happy to work collaboratively with key advisors in obesity and gastrointestinal endoscopy by rapidly developing this protocol to address a huge, emergent unmet need in the field."

Fractyl Health’s lead product candidate, Revita, is based on the company’s insights surrounding the potential role of the gut in obesity and T2D. Revita is designed to remodel the duodenal lining via hydrothermal ablation (i.e., duodenal mucosal resurfacing) to edit abnormal intestinal nutrient sensing and signaling mechanisms that are a potential root cause of metabolic disease. Revita has received a CE mark in Europe and, in January 2022, received reimbursement authorization through NUB in Germany for the treatment of T2D. In the United States, Revita is for investigational use only under US law. A pivotal study of Revita in patients with inadequately controlled T2D despite multiple medicines and insulin, called Revitalize-1, is currently enrolling in the United States and Europe.

Fractyl Health is a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including T2D and obesity. Despite advances in treatment over the last 50 years, T2D and obesity continue to be rapidly growing drivers of morbidity and mortality in the 21st century.