Fractyl Health announces commercial availability of Revita duodenal mucosal resurfacing intervention for type 2 diabetes in Germany – February 8, 2023

German rollout to begin at EVK Hospital in Düsseldorf, with more centers to be added in the future; follows publication of positive two-year REVITA-1 results in February 2022

Fractyl Health announced that its Revita duodenal mucosal resurfacing (DMR) System is now commercially available in Germany. For background, DMR treatment is a minimally invasive outpatient procedure that uses hydrothermal ablation (i.e., targeted application of heated water) to remove excess duodenal mucosa lining within the small intestine that accumulates due to type 2 diabetes and overweight/obesity. The goal of this procedure is to remodel the duodenal lining in order to address abnormal intestinal nutrient sensing and signaling mechanisms that are a potential root cause of metabolic diseases.

In conjunction with today’s update on Revita’s commercial availability, Fractyl also announced that a live demonstration of a Revita procedure was successfully performed at EVK Hospital in Düsseldorf, Germany at the 25^th International Endoscopy Symposium.

Revita’s German rollout will begin at a small scale at EVK Hospital, with additional centers to be added in the future

Fractyl will begin the launch for Revita at a small scale by making the procedure available at EVK Hospital in Düsseldorf, where senior advanced endoscopist Associate Professor Torsten Beyna, Head Physician of the Medical Clinic, will conduct the procedures. Revita will first be available at “select hospitals” in Germany and additional centers will be added in the future. Per the press release, Fractyl recently established reimbursement in Germany under the new examination and treatment methods (NUB) reimbursement process.

• For background, the Revita DMR System received a CE Mark in Europe in April 2016 and has been commercially available in the UK since January 2020. In the US, Revita received FDA Breakthrough Device Designation for use in people with type 2 diabetes who are treated with insulin in April 2021, shortly after Fractyl enrolled its first patient in its pivotal for Revita DMR (REVITALIZE 1) in March 2021. The study is enrolling 428 participants with type 2 diabetes who have inadequate glycemic control on insulin therapy, and primary completion is expected in June 2023.

German launch follows publication of REVITA-1 data showing strong A1c reductions among responders despite limited improvements in insulin resistance at two-year follow-up

Fractyl published two-year REVITA-1 data in February 2022, which showed that the DMR intervention led to an average A1c decrease of 1.4% from a baseline of 8.5% at 24-months among “responders” (n=21). While A1c improvements were maintained at 24 months, HOMA-IR scores, a measure of insulin resistance, were not significantly different at 24 months compared to baseline despite improvements at six and 12 months suggesting that initial improvements in insulin resistance from DMR were not sustained at two-year follow-up.

• Fractyl believes that post-procedure, the duodenum reforms to create a “new, healthy” lining, resulting in improvements in insulin resistance, which is a major challenge in diabetes management. To date, Fractyl has also published positive pilot data for Revita DMR in type 2 diabetes and NASH/NAFLD and in combination with GLP-1 liraglutide for type 2 diabetes. We’re pleased to see Fractyl investing in this novel treatment across the spectrum of type 2 diabetes management and metabolic health, and we look forward to updates on these additional areas of interest.

Close Concerns’ Q&A with Dr. Harith Rajagopalan (CEO)

Q: What sort of training is required for HCPs to perform this procedure?

A: Revita training involves a half day didactic plus hands-on training session with a Revita benchtop simulator we have developed. Because Revita leverages skills that GI endoscopists already have, training has been quite straightforward thus far.

Q: How does Revita plan to get the word out to HCPs about this intervention and promote uptake at the local, national, and international level?

A: Our principal focus in the Germany effort is to generate real world evidence of the effects of Revita in a real-world registry. As you know, despite fabulous clinical trial outcomes, drugs have not delivered the same kind of real world benefits we see from clinical trials. This is mostly due to adherence and side effect issues that are encountered in the real world but not clinical trials. Can a non-drug treatment alternative that does not require ongoing adherence for therapeutic gain offer complementary benefits in the real-world setting? We aim to find out.

Q: What are the potential adverse effects of Revita DMR? Is there any pain associated with the application of heat to the duodenum?

A: In clinical studies thus far, Revita has not been associated with any long-term device or procedure-related adverse events. The mucosa that is ablated with the procedure grows back within several weeks. We have not seen malabsorption, nutrient deficiency, pancreatitis, or infection. Side effects have been mostly mild and transient, gastrointestinal symptoms, typically lasting 1-2 days and consistent with other routine upper endoscopic procedures.

Q: What does Fractyl expect to see in the pivotal trial for Revita?

A: In the ongoing Revitalize-1 pivotal study, patients will be randomized to either the Revita procedure or a sham endoscopic procedure. All subjects in both arms will receive a post-procedure diet for two weeks. The study aims to assess the safety and effectiveness of Revita on improving glucose control in patients who are on insulin therapy.

Q: What is the long-term durability of this procedure? What are the long-term safety concerns (i.e., fibrosis and inflammation)?

A: Results thus far suggest that Revita’s effectiveness can last for 2 years or more from a single procedure. We do not yet know the impact of repeated procedures after that time, but will be eager to assess the need for repeat treatments and the potential benefits of repeat treatments in our ongoing clinical program.

Q: Is there any data on long-term micro- or macrovascular benefits?

A: We are eager for that information, but do not have those data yet.

Q: What are the pros and cons of using Revita DMR as a stand-alone therapy vs. in combination with established “next-gen” therapies like GLP-1s and SGLT-2s?

A: We believe that Revita can be an excellent partner to both GLP-1s and SGLT2is, and some investigators believe Revita may actually help those drugs work even better because of Revita’s complementary mechanism of action. The core question is whether patients are inadequately controlled despite best medical therapy and seeking a non-drug treatment alternative that may offer a different value for them than taking more medicine.

Q: Will Fractyl consider pursuing regulatory submission of Revita DMR for other areas of metabolic disease, such as NASH?

A: Right now, we are focused on developing Revita for T2D. We have two approved pivotal studies: Revitalize-1 is for insulin treated patients and Revitalize-2 is for patients who are on multiple ADAs but not yet on insulin. Benefits seen in other adjacent metabolic indications (NAFLD/NASH, CV disease) will help us consider next steps at that time.

--by April Hopcroft, Claire Holleman, and Kelly Close