Fractyl Health Updates Weight Maintenance Pipeline and Business

Fractyl Health, Inc., a company specializing in metabolic therapies, has announced key updates regarding its clinical studies focused on obesity and type 2 diabetes (T2D). The company is accelerating its REMAIN-1 clinical study, which assesses the efficacy of Revita® in maintaining weight loss after discontinuing GLP-1 therapy. Additionally, an amendment to the protocol for the REVITALIZE-1 study has been approved by the FDA, expanding eligibility to a broader range of T2D patients and increasing the potential U.S. treatment population for Revita from roughly 4 million to about 25 million patients.

Revita is an outpatient endoscopic procedure aimed at resurfacing the mucosal lining of the duodenum, which becomes thickened due to high-fat and high-sugar diets. This thickening impairs the body's ability to maintain a healthy metabolism and blood glucose levels. By resurfacing the duodenal lining, Revita targets the root cause of obesity and T2D, potentially offering a disease-modifying solution.

Harith Rajagopalan, M.D., Ph.D., co-founder and CEO of Fractyl, expressed optimism about the accelerated REMAIN-1 study. He emphasized that if successful, Revita could offer a dependable solution for weight maintenance without the need for continued GLP-1 therapy. Rajagopalan also highlighted the expanded protocol for REVITALIZE-1, which he believes could significantly impact the treatment of T2D by enhancing glucose regulation and slowing disease progression.

Clinical trials have shown that GLP-1 agonists, despite being revolutionary in treating diabetes and obesity, have high discontinuation rates due to side effects and other challenges. Moreover, substantial weight regain, up to 66%, has been observed within a year of stopping GLP-1 therapies. Revita aims to provide more durable solutions by addressing the underlying pathology of the duodenal lining.

REMAIN-1 is a randomized, double-blind trial comparing Revita to a sham procedure in patients who have lost at least 15% of their body weight on tirzepatide therapy. The study will commence in Q3 2024, with a mid-point data analysis expected by Q2 2025. In addition to the randomized trial, an open label cohort, REVEAL-1, will follow a similar patient population, with initial data anticipated in Q4 2024.

REVITALIZE-1 is a sham-controlled, multi-center study that previously included T2D patients taking insulin and up to three non-insulin drugs. With the updated protocol, the study now includes patients inadequately controlled on at least one glucose-lowering agent, broadening the scope and potential impact of the study. Recruitment for the additional patient population will begin immediately, with topline data expected by mid-2025.

Fractyl also presented preclinical data on its GLP-1 pancreatic gene therapy, Rejuva®, at the American Diabetes Association’s 84th Scientific Sessions. The data showed that Rejuva outperformed semaglutide in both the percentage and durability of weight reductions in mice, indicating a promising new avenue for weight loss therapies.

Fractyl Health aims to transform the treatment of metabolic diseases from chronic management to durable, disease-modifying therapies. The company’s lead product, Revita, is designed to remodel the duodenal lining to correct abnormal nutrient sensing and signaling mechanisms, which are believed to be root causes of metabolic diseases like obesity and T2D.

In summary, Fractyl Health is making significant strides in developing therapies that address the root causes of obesity and T2D. With the acceleration of the REMAIN-1 study and the expansion of the REVITALIZE-1 study, the company aims to provide more effective and durable treatment options for millions of patients struggling with these chronic conditions.