REVEAL-1: Sustained post-GLP-1 weight maintenance after a single Revita procedure

Fractyl Health has announced positive 6-month results from its open-label REVEAL-1 Cohort. The REVEAL-1 Cohort is an open-label study in individuals with obesity who have lost at least 15% of their total body weight on a GLP-1 medication and who either need or choose to discontinue GLP-1 therapy.

The REVEAL-1 data show that patients who underwent a single Revita procedure after discontinuing GLP-1 therapy maintained both stable body weight and glycaemic control through 6 months. The new results highlight Revita’s potential as a compelling first-in-class therapy for post-GLP-1 weight maintenance.

To date, 22 participants have been treated in the REVEAL-1 Cohort and are included in safety analyses, with 6-month follow-up efficacy data reported for 17. Three participants withdrew or were lost to follow up and two participants experienced protocol deviations. The profile of the REVEAL-1 Cohort closely mirrors that of the REMAIN-1 Midpoint and Pivotal Cohorts, with an average age of 50 and a gender distribution of 86% women. All 22 participants had previously been treated with a GLP-1 therapy for durations ranging from approximately 5 months to 5 years, with a mean total body weight loss of 24% while on therapy and a mean body weight of 80 kg ± 3 kg (SEM) at the time of intervention.

The key findings include:

• Hard-to-treat GLP-1 responder population: Participants lost 24% total body weight (>50 lbs.) on GLP-1 drugs prior to enrolment (duration on GLP-1 therapy ranging from 5 months to 5 years). Safety and efficacy data through 6 months are available for 22 and 17 participants, respectively.

• Sustained weight maintenance: Participants maintained stable weight after a single Revita procedure, with a mean total body weight change of 1.5% ± 1.3% (SEM; n=17) at 6 months. Published third-party studies report ~10% weight regain by this time point after GLP-1 withdrawal alone (see Figure 1).

• Sustained glycaemic control: Minimal change in HbA1c levels was observed after the Revita procedure (0.04% ± 0.08%; SEM; n=17), compared to the ~0.4% increase in HbA1c seen post-GLP-1 discontinuation in the STEP-1 trial extension of GLP-1 withdrawal. These results indicate the potential for Revita to help stabilize cardiometabolic parameters beyond weight loss alone.

• Stable metabolic trajectory from 1 month to 3 months to 6 months: Mean body weight and HbA1c curves showed a stable and durable trajectory over time, consistent with prior Revita clinical study and real-world experience. These results are encouraging for potential longer-term durability of weight maintenance and metabolic control.

• Excellent tolerability: No procedure-related serious adverse events were observed; 8 of 22 participants (36%) experienced mild treatment-emergent adverse events which were transient and self-limited; all consistent with prior Revita experience and similar to routine upper endoscopy findings.

• Reproducible procedure performance: Average ablation length was approximately 16 cm (n=22), consistent with Revita European real-world experience and the ongoing REMAIN-1 Pivotal study, supporting the potential translatability of results and scalability of technique.

“Many patients desperately need an off-ramp from GLP-1 drugs. These six-month REVEAL-1 results are an important milestone in our understanding of the potential durability and trajectory of post-GLP-1 weight and metabolic maintenance with Revita,” said Dr Adarsh M Thaker, Assistant Clinical Professor, Medicine, David Geffen School of Medicine at UCLA. “We know from experience that most patients begin regaining weight within weeks of stopping GLP-1 therapy, so seeing such sustained effects out to six months after a single Revita procedure is remarkable. This durability points to Revita’s potential as an important new strategy for long-term metabolic health and a new path forward for patients seeking to stay off chronic drug therapy.”