Fractyl Health Accelerates Key Clinical Trials for Obesity and Diabetes Treatments

Fractyl Health, Inc. (NASDAQ:GUTS) (the "Company"), a metabolic therapeutics company focused on pioneering new approaches that treat the root cause of obesity and type 2 diabetes (T2D), today announced that it will accelerate its REMAIN-1 clinical study, which is evaluating Revita's efficacy in maintaining weight loss following the discontinuation of GLP-1 therapy. The Company also announced that the U.S. Food and Drug Administration (FDA) has approved an amendment to the protocol for the REVITALIZE-1 study of its Revita device, which expands eligibility to patients with T2D who are inadequately controlled on any glucose lowering agent, including GLP-1 agonists and/or insulin, thus expanding the potential U.S. treatment population by nearly six-fold. Fractyl now anticipates reporting open label data from the REVEAL-1 cohort of REMAIN-1 starting in Q4 2024, a mid-point data analysis from REMAIN-1 in Q2 2025, and topline data from REVITALIZE-1 in mid-2025.

Obesity is a highly prevalent, complex disease that is associated with multiple cardiometabolic complications, including T2D. GLP-1 agonists have become game-changers in the treatment of diabetes and obesity: over 40% of patients with diabetes in the U.S. have tried GLP-1s and over 12 million U.S. adults have used them just to lose weight,1, 2 yet they are not providing patients with sustained solutions to these chronic problems. Discontinuation rates are high due to gastrointestinal side effects, cost, access challenges, and other unexplained reasons. Clinical trials have highlighted the risk of substantial weight regain — as much as 66% — within one year of discontinuing GLP-1 therapies.3, 4

Revita is an outpatient endoscopic procedure that involves resurfacing the mucosal lining of the duodenum, the first part of the small intestine just after the stomach, which is responsible for breaking down food into absorbable nutrients. Revita targets the duodenal lining, which can become thickened by high-fat and high-sugar diets, making it hard for the body to maintain a healthy metabolism and blood glucose levels. By resurfacing and reversing the pathology of the duodenal lining, if approved, Revita has the potential to become the first disease-modifying therapy that targets a root cause of obesity and T2D.

"We are pleased to announce the acceleration of our REMAIN-1 study to address the significant unmet need we're seeing around weight maintenance following the use of GLP-1 treatment," said Harith Rajagopalan, M.D., Ph.D., co-founder and Chief Executive Officer of Fractyl. "If successful and approved, Revita may offer a reliable ‘off-ramp' to the millions of people currently taking GLP-1 therapies, potentially providing durable weight maintenance without having to continue taking these medications."

Dr. Rajagopalan added, "In parallel, we are excited about the expansion of the protocol for REVITALIZE-1, because we believe Revita holds unique potential for tackling disease progression and prevention in the huge public health crisis that is T2D. For patients currently managing T2D with medications and/or insulin, Revita aims to enhance glucose regulation and halt or slow down the disease's advancement, representing a paradigm shift in the way in which we treat these patients."

In prior clinical studies of Revita conducted in people with T2D in the U.S. and EU, pooled analyses of weight data provided evidence to support the potential for durable weight maintenance after a single Revita procedure. Revita is approved in Germany for the treatment of T2D and has both an FDA Breakthrough Device designation in insulin-treated T2D and reimbursement support from the CMS, meaning that CMS will cover routine costs and certain trial-related expenses for participants.

REMAIN-1 Update

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, which is expected to begin in Q3 2024. Given the accelerated timeline, the Company now anticipates a mid-point data analysis from this cohort in Q2 2025. In parallel to the randomized portion of the REMAIN-1 study, Fractyl will also have an open label cohort, REVEAL-1, that will follow a similar patient population and management protocol with open label data updates. The Company anticipates providing initial open label data in Q4 2024.

REVITALIZE-1 Update

REVITALIZE-1 (NCT04419779) is a randomized, double-blind crossover, sham-controlled, multi-center study of Revita. Previously, the protocol included T2D patients taking insulin and up to three non-insulin drugs, including GLP-1 therapies. The updated protocol will now include patients with inadequately controlled T2D on at least one glucose lowering agent (GLA). Fractyl will immediately begin recruiting these additional patients into REVITALIZE-1 and now expects to report topline data in mid-2025.  

REJUVA Update

The Company presented new head-to-head preclinical data comparing Rejuva®, its adeno-associated virus (AAV)-based GLP-1 pancreatic gene therapy program, to semaglutide as part of a President Select Abstract at ADA's 84th Scientific Sessions in Orlando, FL. These data demonstrated statistically significant improvements in the percentage and durability of weight reductions as well as a greater relative proportion of fat mass to lean mass loss in mice treated with Rejuva vs. semaglutide.