Response’s Investigational Small Molecule Inhibitor Shows Promising Post-GLP-1 Weight Management, Cardiometabolic Benefits

Author(s):

Key Takeaways

RDX-002 significantly reduced postprandial triglycerides and weight regain in patients post-GLP-1 therapy, showing potential in obesity management.
The trial reported no serious adverse events, with most being mild gastrointestinal issues that resolved early in treatment.
RDX-002's mechanism may complement GLP-1 therapies, offering a durable solution for long-term weight management and cardiometabolic health.
Obesity prevalence in the U.S. has increased, highlighting the need for effective long-term management strategies.

Results from a Phase II trial (NCT06640972) showed that patients treated with RDX-002 experienced significant reductions in postprandial triglycerides, less weight regain after GLP-1 therapy, and improvements in key cardiometabolic markers.

Image Credit: Adobe Stock Images/WavebreakMediaMicro

Topline Findings

Significant triglyceride reduction: RDX-002 lowered postprandial triglycerides by 93.5% versus placebo at week 12 in adults recently discontinuing GLP-1 therapy.
Less weight regain: Patients on RDX-002 experienced 34% less weight regain and smaller increases in total body fat compared with placebo.
Favorable safety profile: No serious adverse events were reported, with only mild-to-moderate gastrointestinal effects that resolved early in treatment.

Results from a Phase II trial (NCT06640972) show that Response Pharmaceuticals’ RDX-002 demonstrated statistically significant reductions in postprandial triglycerides and was associated with less weight regain, improvements in total body fat, and favorable cardiometabolic effects in patients following GLP-1 receptor agonist therapy. The novel selective inhibitor of intestinal microsomal triglyceride transfer protein (iMTP) also maintained a well-tolerated safety profile. Full data from the trial are expected to be presented at an upcoming scientific meeting.¹

Could RDX-002 Unlock a New Era in Post-GLP-1 Weight Management?

“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,” said William Sasiela, chief medical officer, Response Pharmaceuticals, in a press release. “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, and we look forward to confirming the durability of these effects in the ongoing open-label extension study. We also believe that these data support future clinical studies in related settings including the use of RDX-002 in combination with GLP-1RA therapy and other related medications where our distinct mechanism of action may work synergistically.”

Trial Design

The randomized, double-blind, placebo-controlled, parallel-group trial evaluated the efficacy and safety of RDX-002 in 68 adults who recently discontinued GLP-1 receptor agonist therapy for obesity.
All eligible patients were required to have lost at least 10% of their original body weight, with plans to stop GLP-1 therapy.
Patients were randomly assigned to receive either 200 mg of RDX-002 twice daily or placebo over 12 weeks, with clinic visits every four weeks for monitoring.
The primary endpoint of the trial was to assess whether RDX-002 reduced postprandial triglycerides following a high-fat meal.
Key secondary endpoints included change in mean percent body weight, proportion of patients achieving at least 5% change in body weight, and the difference in the mean percent change from baseline in low-density lipoprotein cholesterol.²

Key Findings

RDX-002 treatment led to a mean reduction of –227.3 mghr/dL in postprandial triglycerides at week 12 compared with a placebo increase of +64.1 mghr/dL, representing a 93.5% least squares mean difference (p<0.001).
Patients receiving RDX-002 also experienced 34% less weight regain after discontinuing GLP-1 therapy (–2.92% vs. placebo; p=0.019), with exploratory analyses suggesting smaller increases in total body fat mass (1.99% vs. 6.71% for placebo).
No serious adverse events (AEs) or treatment discontinuations were reported.
Most AEs were mild to moderate gastrointestinal issues that generally resolved early in treatment.¹

“These Phase II results underscore the potential of our approach to address the most critical gap in obesity care following GLP-1 therapy,” said Eric Keller, CEO, Response Pharmaceuticals, in the press release. “By targeting key pathways involved in metabolic regulation, we aim to provide a durable, well-tolerated solution that supports long-term weight management and cardiometabolic health. We remain committed to advancing the development of RDX-002 in our lead indication—antipsychotic-induced weight gain (AIWG)—targeting a highly metabolically vulnerable population, as well as exploring its potential in other areas with significant unmet metabolic need.”

Obesity Context

According to the Centers for Disease Control and Prevention, more than two out of every five adults in the United States are currently living with obesity.
Notably, the prevalence of obesity in the United States increased from 30.5% in 1999-2000 to 41.9% in 2017–March 2020.
Approximately 23% of adults with obesity also have diabetes, while 58% also have high blood pressure.³

“GLP-1 receptor agonist therapies have revolutionized obesity treatment, but they are not the end of the story,” said Chris Packard, professor, Institute of Cardiovascular and Medical Sciences, University of Glasgow, in the press release. “Many people regain weight and experience the return of an adverse cardiometabolic profile after stopping GLP-1RA therapy. 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.”

References

Response Pharmaceuticals Announces Positive Top-Line Results From Phase 2 Study of RDX-002 in Post-GLP-1 Management. BusinessWire. August 13, 2025. Accessed August 13, 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
Effects of RDX-002 on Postprandial Triglycerides in Patients Discontinuing GLP-1 Agonists. Clinicaltrials.gov. Accessed August 13, 2025. https://clinicaltrials.gov/study/NCT06640972
Adult Obesity Facts. CDC. Accessed August 13, 2025. https://www.cdc.gov/obesity/adult-obesity-facts/index.html#:~:text=At%20a%20glance,BMI%20of%2040.0%20or%20higher.

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