Ventyx Biosciences has revealed promising endoscopic response data from its Phase 2 trial of VTX958, an allosteric TYK2 inhibitor, in patients with Crohn's disease, despite not meeting the primary endpoint based on symptomatic improvement.
The randomized, double-blind, placebo-controlled study enrolled 109 patients with moderately-to-severely active Crohn's disease, evaluating two dose levels of VTX958 (225mg and 300mg BID) against placebo over a 12-week induction period.
While the trial did not achieve its primary endpoint of change in Crohn's Disease Activity Index (CDAI) due to an unexpectedly high placebo response, the drug demonstrated significant improvements in objective measures of disease activity.
Strong Endoscopic Response Data
The most compelling evidence of VTX958's efficacy came from endoscopic assessments. Patients receiving the 300mg dose showed a 32.4% endoscopic response rate (p=0.0066), while the 225mg group achieved a 24.3% response rate (p=0.0263), compared to just 5.7% in the placebo group. Endoscopic response was defined as a ≥50% reduction from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD).
Biomarker Improvements and Combined Endpoints
The drug's efficacy was further supported by improvements in key inflammatory markers. A notable 43.2% of patients in the 300mg group achieved a clinical-biomarker response, compared to 14.3% in the placebo group (p=0.0105). This composite endpoint required either a significant CDAI improvement or clinical remission, combined with substantial reductions in inflammatory markers.
"These Phase 2 data suggest that VTX958 has the potential for disease-modifying benefit in Crohn's disease, including strong effects on endoscopic response," stated Dr. Silvio Danese, Professor of Gastroenterology at Vita-Salute San Raffaele University. "The totality of the Phase 2 data for VTX958, including a favorable safety profile, warrant further investigation in future clinical trials."
Clinical Implications and Future Development
The disconnect between symptomatic and endoscopic responses has precedent in Crohn's disease trials. Raju Mohan, PhD, Founder and CEO of Ventyx, suggested that longer treatment duration could potentially demonstrate greater placebo-adjusted clinical remission rates and reduced placebo response on symptomatic measures.
The company is continuing to analyze data from the 52-week long-term extension phase, which will inform future development strategy and partnership opportunities. The results position VTX958 as a potential new oral therapy option in a field where safe and effective oral treatments remain an unmet need.
Safety and Tolerability
Throughout the Phase 2 trial, VTX958 demonstrated a favorable safety profile, an important consideration for chronic inflammatory conditions requiring long-term treatment. This safety profile, combined with the convenience of oral administration, could potentially offer advantages over existing injectable therapies.
