Wave Life Sciences reports Phase 1 INLIGHT trial data showing WVE-007 reduced visceral fat with preserved muscle mass after a single dose in individuals with overweight or obesity.
Written By: Karthik Teja Macharla, PharmD
Reviewed By: Pharmacally Editorial Team
Wave Life Sciences reported new six-month data from the Phase 1 portion of the INLIGHT clinical trial evaluating WVE-007, an investigational INHBE-targeting GalNAc-siRNA therapy for obesity and cardiometabolic conditions. Results from the early study suggest a single dose can reduce harmful visceral fat while preserving muscle mass in individuals living with overweight or obesity.
The findings come from the single-ascending dose (SAD) portion of the randomized, placebo-controlled INLIGHT trial (NCT06842186). In the 240 mg cohort, participants receiving a single dose of WVE-007 showed improvements in body composition after six months of follow-up, including statistically significant reductions in visceral fat and clinically meaningful decreases in waist circumference, along with modest reductions in body weight.
The cohort included 32 participants with an average BMI of 32 kg/m². After six months, visceral fat mass decreased 14.3% from baseline, total fat mass declined 5.3%, and lean mass increased 2.4%, based on DEXA body composition measurements. Waist circumference decreased 3.3%, while body weight declined 0.9%.
Wave also reported improvements in the visceral fat-to-muscle ratio (VMR), a composite measure of visceral fat and lean mass. In the INLIGHT trial, VMR declined 16.5% from baseline following a single 240 mg dose of WVE-007. By comparison, VMR reductions of 12.2% were reported after six months of weekly 2.4 mg semaglutide in the Phase 2 BELIEVE trial, which enrolled participants with a higher average BMI of 37 kg/m².
WVE-007 is designed to silence INHBE mRNA, which reduces production of the downstream protein Activin E, a liver-derived signaling protein involved in regulating fat metabolism. When Activin E levels decrease, fat cells increase lipolysis, the process that breaks down stored triglycerides into fatty acids. This leads to a reduction in body fat, particularly visceral fat. Unlike many weight-loss treatments that can also reduce lean tissue, lowering Activin E primarily affects adipose tissue metabolism, allowing fat loss while largely preserving skeletal muscle mass.
The therapy also showed durable target engagement, with serum Activin E reductions sustained for at least seven months and reaching a mean maximum reduction of up to 88%, supporting potential once- or twice-yearly dosing.
WVE-007 has been generally safe and well tolerated, with no treatment discontinuations or serious treatment-emergent adverse events reported. All treatment-related adverse events were mild, and no clinically meaningful laboratory changes were observed.
Additional data from the 400 mg cohort showed placebo-adjusted reductions in visceral fat (-5.0%) and total fat (-0.7%) at three months, with lean mass largely preserved (-0.2%). A post-hoc analysis showed greater visceral fat reduction (-7.8%, p<0.05) in participants with higher baseline visceral fat levels.
Wave plans to initiate the Phase 2a multidose portion of INLIGHT in the second quarter of 2026, enrolling individuals with BMI 35–50 kg/m² and comorbidities. Additional updates from the program, including data from the 600 mg Phase 1 cohort, are expected in 2026.
References
Wave Life Sciences Announces Positive Interim Phase 1 Data from INLIGHT: Further Improvements in Body Composition, with Clinically Meaningful Reductions in Visceral Fat and Waist Circumference, at Six Months Following Single Dose of WVE-007, 26 March 2026, https://ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-positive-interim-phase-1-data
A Phase 1 Study of WVE-007 in Adults Living with Overweight or Obesity (INLIGHT), ClinicalTrials.gov ID NCT06842186, https://clinicaltrials.gov/study/NCT06842186
About the Writer
Karthik Teja Macharla, PharmD is a Pharm.D. graduate with a strong interest in clinical research, pharmacovigilance, and medical writing. In his words, he is passionate about converting complex medical information into clear, evidence-based scientific communication, committed to contributing to patient safety and advancing healthcare through accurate and impactful medical content.