Ventyx Biosciences announced positive phase 2 results for its oral NLRP3 inhibitor, VTX3232, in patients with obesity and cardiovascular risk factors. The study showed the investigational therapy achieved substantial reductions in inflammatory biomarkers, including an almost 80% decrease in high-sensitivity C-reactive protein (hsCRP) within the first week of dosing.
The randomized, double-blind, placebo-controlled trial enrolled 175 participants with body mass index (BMI) values between 30.0 and 42.0 kg/m² and hsCRP levels above 2 mg/L. Patients were divided into four groups receiving either VTX3232 or placebo, both as monotherapies and in combination with Novo Nordisk’s semaglutide. The trial’s primary goal was to evaluate safety and tolerability, while secondary measures focused on the drug’s effect on hsCRP and other inflammatory biomarkers.
VTX3232 was found to be safe and well-tolerated both alone and in combination with semaglutide. Treatment-emergent adverse events occurred in 46% of patients in the VTX3232 group and 49% of those on placebo.
Similar rates were observed between the semaglutide-containing groups, with 56% of participants in each experiencing such events. Severe adverse events and discontinuations were balanced across treatment arms.
When assessing efficacy, VTX3232 demonstrated a 78% reduction in hsCRP compared with a 3% increase in the placebo cohort at 12 weeks in the modified analysis set. In the full analysis set, reductions of 64% were reported compared to a 3% increase among placebo recipients. Nearly 69% of patients achieved hsCRP levels below 2 mg/L, a threshold associated with reduced cardiovascular risk.
In addition to lowering hsCRP, VTX3232 monotherapy significantly reduced interleukin-6 (IL-6) levels to a median of 1.60 ng/L, below the cardiovascular risk threshold of 1.65 ng/L. The therapy also produced statistically significant decreases in lipoprotein(a) [Lp(a)], fibrinogen, and erythrocyte sedimentation rate (ESR). No changes were observed in other lipid parameters, and the treatment did not result in weight loss.
The combination of VTX3232 and semaglutide showed enhanced benefits compared to semaglutide alone, achieving further reductions in hsCRP, IL-6, Lp(a), fibrinogen, ESR, and liver inflammation. Among participants with at least 5% baseline liver fat, the combination treatment produced a statistically significant decline in liver inflammation as measured by corrected T1 MRI.
Ventyx’s Chief Executive Officer, Raju Mohan, Ph.D., said, “We are very pleased with the results of this study where an ~80% reduction in hsCRP was achieved within the first week of dosing and maintained throughout the full 12-week dosing period in participants with measurable drug levels.” He added that nearly 70% of participants reached target hsCRP levels and that the findings support further investigation into VTX3232’s potential as an oral anti-inflammatory therapy.
Chief Medical Officer Mark Forman, M.D., Ph.D., said the results showed robust inhibition of the NLRP3 pathway and an encouraging safety profile. He added that combining VTX3232 with semaglutide led to additional reductions in key inflammatory markers and liver inflammation.
Ventyx intends to present additional data at upcoming medical conferences and will provide updates on the continued development of VTX3232 in future disclosures. The company is also investigating VTX3232 in an ongoing phase 2 study for Parkinson’s disease.
