Novel Mechanism Demonstrates Clinically Meaningful Prevention of Weight Rebound and Metabolic Benefits After Stopping GLP-1 Therapy
- Primary Endpoint met: Statistically significant reduction in blood-fat levels after eating (-51.9%)
- Multiple secondary endpoints met: Including statistically significant reduction in weight regain (-34%) compared to placebo, and improvement in cardiometabolic risk factors with RDX-002
- Favorable safety and tolerability profile: No SAEs or discontinuation due to AEs consistent with prior studies
FALLS CHURCH, Va.--(BUSINESS WIRE)--#AIWG--Response Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing next-generation therapies for weight management and metabolic health, today announced positive top-line results from its double-blind, placebo-controlled Phase 2 clinical trial evaluating RDX-002 in individuals who have previously completed a course of GLP-1 Receptor Agonist therapy for obesity. The study (NCT06640972) enrolled 68 participants at a single US site, evaluating the safety, efficacy, and metabolic impact of RDX-002 monotherapy in a post-GLP-1 setting.
While GLP-1 Receptor Agonist therapies have advanced the treatment of obesity, multiple analyses have shown that most people discontinue treatment by 12 months, often due to cost or tolerability. As a result, many individuals face challenges maintaining their weight loss and the accompanying metabolic benefits, highlighting a critical unmet need in the post-GLP-1RA setting.
RDX-002, an investigational agent that is a selective inhibitor of intestinal microsomal triglyceride transfer protein (iMTP) — a critical chaperone protein involved in the intestinal absorption of dietary triglycerides and cholesterol — demonstrated statistically significant reductions in blood fat-levels after eating (post-prandial triglycerides) and an associated reduction in weight regain versus placebo over 12 weeks of treatment.
“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 Dr. William Sasiela, Chief Medical Officer of Response Pharmaceuticals. “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.”
Key Highlights from the Phase 2 Trial:
- Mean reduction of –227.3 mg*hr/dL in postprandial triglycerides (area under the response curve) at Week 12 versus placebo change of +64.1 mg*hr/ml (LS mean difference of -93.5%; p<0.001)
- Individuals receiving RDX-002 gained less weight after GLP-1 discontinuation: -2.92% (-34% relative difference) versus placebo (p=0.019); exploratory analyses also suggest a corresponding difference in total body fat mass change (mean percent change at week 12 of 1.99% for RDX-002 vs. 6.71% for placebo).
- Improved markers of cardiometabolic health, including blood pressure and high-sensitivity C-reactive protein (hsCRP)
- Favorable safety and tolerability profile consistent with prior studies with no serious adverse events (SAEs) or discontinuations and mild to moderate gastrointestinal AEs that generally resolved early in treatment
- Sustained efficacy in individuals recently completing GLP-1 receptor agonist therapy over 12 weeks, which will be further confirmed with an ongoing 24-week open label extension (OLE)
“These Phase 2 results underscore the potential of our approach to address the most critical gap in obesity care following GLP-1 therapy,” said Response Pharmaceuticals’ Chief Executive Officer, Eric Keller. “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.”
“GLP-1 Receptor Agonist therapies have revolutionized obesity treatment, but they are not the end of the story,” said Professor Chris Packard, Institute of Cardiovascular and Medical Sciences, University of Glasgow. “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.”
Full data from this Phase 2 study will be presented at an upcoming scientific meeting. Response Pharmaceuticals plans to further evaluate the safety and efficacy of RDX-002 for the treatment of AIWG, and other weight management indications.
About Response Pharmaceuticals
Response Pharmaceuticals is a clinical-stage biopharmaceutical company developing therapies for weight management and metabolic health in high-need populations. The company’s lead programs focus on addressing antipsychotic-induced weight gain in patients with serious mental illness and supporting individuals transitioning off weight loss drugs in maintaining their weight loss and cardiometabolic benefits. Adjunctive Phase 2 studies are being explored in settings marked by significant weight gain or metabolic disruption, including potential combination use with other therapies.
About RDX-002
RDX-002, Response Pharmaceuticals’ lead candidate, is an investigational first-in-class, potent, selective, and gut-specific small molecule inhibitor of intestinal microsomal triglyceride transfer protein (iMTP). The overall effect of iMTP inhibition is a reduction in the post-meal uptake of triglycerides (fat)—and thus calories—and cholesterol by the body. RDX-002 is being developed as a therapy to address drug-induced weight gain and decrease cardiometabolic risk, including in patients taking life-saving anti-psychotic medications and those discontinuing GLP-1 Receptor Agonists for the treatment of obesity. RDX-002 has been studied in multiple Phase 1 and Phase 2 clinical trials in more than 450 healthy subjects and patients dosed up to 84 days. In these studies, RDX-002 lowered post-prandial triglyceride levels and circulating levels of low-density lipoprotein cholesterol (LDL-C), and reduced weight. RDX-002 was generally well-tolerated, with adverse events restricted to mostly mild to moderate gastrointestinal effects. No serious adverse events have been attributed to RDX-002. RDX-002 is being developed under an exclusive world-wide license from Sanofi S.A.
For more information, please visit https://www.responsepharmaceuticals.com.
Contacts
Press and Investor Contact
Sabine Bisson, PhD
Chief Operating Officer, Response Pharmaceuticals Inc.
press@responsepharmaceuticals.com
