Response Pharmaceuticals Reports Phase 2 Data for RDX-002 Weight Management After GLP-1 Discontinuation
Virginia-based Response Pharmaceuticals announced 36-week Phase 2 data for RDX-002, a gut-restricted inhibitor of intestinal microsomal triglyceride transfer protein (iMTP), in patients who had discontinued GLP-1 receptor agonist therapy for obesity. The Response Pharmaceuticals RDX-002 program targets a specific clinical scenario — post-GLP-1 weight management — where patients commonly regain the majority of lost weight within a year of stopping treatment.
Trial specifics
The Phase 2 study enrolled 68 participants following planned discontinuation of GLP-1 receptor agonist treatment. The trial consisted of a 12-week randomized, double-blind, placebo-controlled period followed by a 24-week open-label extension. The primary endpoint was reduction of postprandial triglyceride response to a standardized high-fat meal, measured by area under the curve. RDX-002 Phase 2 data showed a 93.5% reduction in postprandial triglyceride AUC versus placebo at Week 12 (p<0.001). By Week 36, subjects on RDX-002 preserved 57% of weight loss previously achieved with GLP-1 receptor agonist therapy. Participants who crossed over from placebo to RDX-002 during the open-label extension saw their rate of weight regain fall from 0.58% per week to 0.14% per week. Over the initial 12-week controlled period, total body fat mass gain was 1.99% with RDX-002 versus 6.71% with placebo. Blood pressure and high-sensitivity C-reactive protein also showed treatment-related improvements. The drug was generally well-tolerated; gastrointestinal events — primarily diarrhea, nausea, and abdominal pain — were mild to moderate and largely transient, concentrating in the first two weeks of treatment. One patient in each arm discontinued due to an adverse event, and no serious adverse events were attributed to RDX-002. The specific dosing regimen was not disclosed.
"While GLP-1 agonists are highly effective at reducing weight, 65% of patients discontinue GLP-1 agonist treatment within one year of starting," said Dr. William Sasiela, Chief Medical Officer. The company is now planning a Phase 2 study of RDX-002 in antipsychotic-induced weight gain, a population with elevated cardiometabolic risk. RDX-002 has no prior regulatory approvals; it is being developed under an exclusive worldwide license from Sanofi S.A. and has been studied in more than 450 subjects across multiple Phase I and Phase II trials.
Research context
RDX-002 inhibits MTP selectively within intestinal enterocytes, blocking assembly of chylomicrons and thereby reducing dietary triglyceride and cholesterol absorption. This gut-restricted design distinguishes it from lomitapide (Juxtapid), a systemic MTP inhibitor approved for homozygous familial hypercholesterolemia, which carries hepatotoxicity risks due to hepatic VLDL secretion blockade. By confining activity to the intestine, RDX-002 aims to reduce caloric uptake from fat without systemic lipid accumulation in the liver.