Poor tolerability of GLP-1 obesity drugs leads many patients to stop taking them, resulting in gaining back the weight that was lost. Some drug companies are trying to develop other approaches that could serve as maintenance therapies following initial treatment with GLP-1 injections, and Response Pharmaceuticals now has encouraging mid-stage clinical data building the case for its pill.
The Response drug, RDX-002, is an oral small molecule designed to inhibit a target called intestinal microsomal triglyceride transfer protein (iMTP). The Falls Church, Virginia-based biotech says this approach reduces the uptake of triglycerides (fats) and cholesterol by the body. Consequently, the body takes in fewer calories.
Response evaluated RDX-002, taken as a twice-daily pill, in a Phase 2 test that enrolled 68 participants who had stopped or were willing to discontinue the Novo Nordisk GLP-1 drug Wegovy or the Eli Lilly GLP-1 and GIP receptor agonist Zepbound. The main goal was to measure the change in triglyceride levels, compared to placebo, after 12 weeks. Secondary goals include measuring the change in body weight and cholesterol levels.
According to results released Wednesday, Response’s drug let to statistically significant reductions in fat levels in the blood after eating. Furthermore, results at 12 weeks showed these reductions were also associated with reduction in weight regain compared to a placebo. The startup said RDX-002 was generally well-tolerated, characterizing adverse events as mostly mild-to-moderate gastrointestinal effects. No serious adverse events were reported. The company said full Phase 2 data will be presented at an upcoming scientific meeting.
RDX-002 was discovered and initially developed by Surface Logix, a biotech that was acquired by Kadmon Pharmaceuticals. In 2021, Sanofi paid $1.9 billion to acquire Kadmon, a deal focused mainly on Rezurock, a ROCK2 inhibitor that reached the market as a treatment for chronic graft-versus-host disease. Response licensed global rights to RDX-002 from Sanofi. According to Response’s website, company co-founder and Chief Scientific Officer Paul Sweetnam led the discovery of RDX-002 at Surface Logix. Response announced an $8 million Series A financing in 2022.
The lead indication for RDX-002 is addressing weight gain from antipsychotics, a common side effect of these medications. A separate Phase 2 program is ongoing in this indication. But helping patients maintain weight loss following GLP-1 treatment opens up another opportunity for the biotech.
“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,” Response CEO Eric Keller said in a prepared statement. “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.”
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