RDX-002 Hits Primary and Secondary Endpoints for Post-GLP-1 Weight Management

Response Pharmaceuticals has reported positive top-line findings from a phase 2 trial of its investigational agent RDX-002, in development to help maintain weight loss and metabolic improvements after discontinuation of GLP-1 receptor agonist (GLP-1) therapy for obesity.

The randomized, double-blind, placebo-controlled study (NCT06640972) enrolled 68 adults at a single US site who had recently completed a course of incretin-based antiobesity medication, either semaglutide (Wegovy; Novo Nordisk) or tirzepatide (Zepbound; Eli Lilly), and had lost at least 10% of their original body weight or 10 kg. Participants received 12 weeks of RDX-002 or placebo.

Weight Regained Slowed

RDX-002 met its primary endpoint, producing a statistically significant mean reduction of –227.3 mg x hr/dL in postprandial triglycerides (area under the response curve) at week 12, compared with a placebo change of +64.1 mg x hr/dL, according to the Response news release. Participants who received the study drug also gained less weight following GLP-1 discontinuation. Investigators reported a 34% relative reduction in regain in the RDX-002 treatment arm vs placebo (–2.92% vs. placebo; P =.019).

Response also reported results of exploratory analyses that showed smaller increases in total body fat mass with RDX-002 (mean change 1.99%) compared with placebo (6.71%). Blood pressure and hsC-reactive protein values also improved. Safety and tolerability profiles were favorable, the company said, with no serious adverse events (SAEs) or treatment discontinuations. Sustained efficacy will be further evaluated in an ongoing 24-week open-label extension.

RDX-002 is a first-in-class, gut-specific small-molecule inhibitor of intestinal microsomal triglyceride (TG) transfer protein (iMTP), described as a chaperone protein that mediates intestinal absorption of dietary TGs and cholesterol. By limiting post-meal fat uptake, iMTP inhibition may reduce caloric absorption and improve lipid metabolism.

"Critical Gap" in Obesity Care

“These results confirm our data from prior studies and highlight RDX-002’s potential to address what is recognized increasingly as a critical gap in obesity management following GLP-1RA therapy,” William Sasiela, PhD, Response Pharmaceuticals chief medical officer, said in the statement. “We believe this mechanism of action offers a differentiated and complementary approach to help patients maintain and over the long term enhance the health benefits they achieve with GLP-1s.”

GLP-1 therapy discontinuation rates top 50% within a year of initiation, often as a result of tolerability or cost. Moreover, weight regain after treatment cessation has been widely observed, regardless of lifestyle interventions. A recent meta-analysis found mean weight regain after stopping semaglutide/tirzepatide of nearly 10 kg. "The proportion of weight regained was proportional to the amount originally lost," the authors noted.

With weight regain comes the potential for rapid deterioration of improved cardiometabolic risk factors, the additional benefit observed in this study and a known class effect.

“Many people regain weight and experience the return of an adverse cardiometabolic profile after stopping GLP-1RA therapy,” Chris Packard, PhD, Institute of Cardiovascular and Medical Sciences, University of Glasgow, said in the statement. “A novel treatment that can sustain and build upon the gains achieved with GLP-1 receptor agonists presents a potentially important advance in long-term obesity care.”

RDX-002 Past, Future

In multiple phase 1 and 2 studies including more than 450 participants, the investigational iMTP inhibitor has demonstrated reductions in postprandial triglycerides, LDL-C, and body weight, with mostly mild to moderate gastrointestinal adverse events. No SAEs have been attributed to the drug in prior studies

Response Pharmaceuticals plans to advance RDX-002 for additional indications, including antipsychotic-induced weight gain—a condition associated with high cardiometabolic risk—and to explore its use in combination with GLP-1RAs and other metabolic therapies. Full Phase 2 results will be presented at an upcoming scientific meeting.

References

Response Pharmaceuticals announces positive top-line results from phae 2 sutdy of RDX-002 in post-GLP-1 management. News release. Response Pharmaceuticals. August 13, 2025. Accessed August 14, 2025. https://www.businesswire.com/news/home/20250813869741/en/Response-Pharmaceuticals-Announces-Positive-Top-Line-Results-From-Phase-2-Study-of-RDX-002-in-Post-GLP-1-Management

Berg S, Stickle H, Rose SJ, Nemec EC. Discontinuing glucagon-like peptide-1 receptor agonists and body habitus: A systematic review and meta-analysis. Obesity Rev. 2025;26(8):e13929. doi:10.1111/obr.13929