공지 • Mar 28
Wave Life Sciences Ltd. Announces Positive Interim Phase 1 Data From INLIGHT
Wave Life Sciences Ltd. announced new data from the Phase 1 portion of its first-in-human INLIGHT trial evaluating WVE-007, an investigational INHBE GalNAc-siRNA (SpiNA design), in otherwise healthy individuals living with overweight or obesity. After six months of follow-up, a single 240 mg dose led to further improvements in body composition, including fat loss with muscle preservation, with clinically meaningful reductions in visceral fat and waist circumference in a population with less fat and lower BMI than those in Phase 2 and 3 obesity studies. At 6-month follow-up, a single 240 mg dose of WVE-007 (INHBE GalNAc-siRNA) continued to drive significant placebo-adjusted reductions in visceral fat (-14%). WVE-007 led to greater improvement in body composition (visceral fat-to-muscle ratio) at six months versus that seen with weekly GLP-1 in later-stage trial (BMI: ~37 kg/m2), even with participants in Phase 1 portion of INLIGHT having substantially lower BMI (~32 kg/m2) and lower levels of fat than those in Phase 2 and 3 obesity studies. Durable and dose-dependent suppression of serum Activin E sustained through at least seven months continues to support expectations for once or twice-yearly dosing. WVE-007 continues to be generally safe and well tolerated. In the 240 mg cohort, six-month data demonstrated further improvements in body composition following a single dose of WVE-007, with statistically significant reductions in visceral fat and clinically meaningful reductions in waist circumference, as well as reductions in body weight. There were 32 participants in the 240 mg cohort (3:1 treatment to placebo) that had an average BMI of 32 kg/m2 and less visceral and subcutaneous fat than those in Phase 2 or 3 obesity studies. Placebo-adjusted percent change from baseline* 240 mg 3-month follow-up 6-month follow-up DEXA Visceral fat mass -7.8% -14.3% Total fat mass -5.1% -5.3% Lean mass +2.2% +2.4% Clinical measurements Waist circumference -0.4% -3.3% Body weight -0.3% -0.9%. The results were analyzed with a pre-specified statistical analysis (MMRM) utilizing all available data across all timepoints and dose groups at the time of the current data analysis and utilizing a pooled placebo comparator. The improvement in body composition as measured by visceral fat-to-muscle ratio (VMR) observed with a single 240 mg dose of WVE-007 (-16.5% vs. baseline) in the Phase 1 INLIGHT trial was greater than that achieved with weekly 2.4 mg doses of semaglutide at six months (-12.2% vs. baseline) in the BELIEVE Phase 2 clinical trial, which enrolled a higher BMI population (average 37 kg/m²). VMR is an established measure of body composition integrating harmful visceral fat and beneficial lean mass into a single index. Lower VMR is associated with a decreased risk of MASH, type 2 diabetes, and cardiometabolic disorders. Consistent, durable, and dose-dependent serum Activin E reductions sustained through at least seven months continue to support WVE-007’s potential for once or twice-yearly dosing, with a mean maximum reduction of up to 88%. WVE-007 continues to be generally safe and well tolerated to date up to 600 mg. There were no treatment discontinuations, and no severe or serious treatment emergent adverse events (TEAEs). All TEAEs in the treatment groups were mild or moderate, and all treatment-related adverse events were mild. There were no clinically meaningful changes in clinical laboratory measurements, including lipid profiles or liver function tests. In the 400 mg cohort, three-month data demonstrated placebo-adjusted reductions in visceral fat (-5.0%), total fat (-0.7%), with lean mass preservation (-0.2%) from baseline following a single dose. Notably, the 400 mg cohort had a leaner baseline body composition, with lower BMI and more participants (10 out of 24 individuals) with healthy levels of visceral fat (=500 g). A post-hoc analysis of the three-month results demonstrated a more robust and statistically significant average reduction in visceral fat (-7.8%, p500g), similar to that observed in the 240 mg cohort. These results emphasize the impact of baseline body composition on therapeutic effect and support expectations that evaluating individuals with higher BMI and visceral fat at baseline will lead to greater improvements in body composition and weight loss. Wave is on track to initiate the Phase 2a multidose portion of INLIGHT evaluating WVE-007 as monotherapy in individuals with higher BMI (35-50 kg/m2) and comorbidities in the second quarter of 2026. This placebo-controlled (3:1) Phase 2a study will include multiple assessments over a 12-month period, including body weight, waist circumference, body composition (MRI and DEXA), liver fat (MRI-PDFF), HbA1c, lipid levels, CRP, and muscle function. The study is expected to demonstrate further body composition improvements, including greater fat loss with preserved muscle, and additional weight loss. The results will inform further development of WVE-007 in obesity, as well as MASH, type 2 diabetes, and cardiovascular disease. The first assessment in this portion of the trial is planned for three months after participants have received their first dose. Additional data from INLIGHT, including data from the 600 mg Phase 1 SAD cohort, are expected in 2026. Wave expects to initiate the Phase 2a multidose portion of INLIGHT in individuals with higher BMI and comorbidities in the second quarter of 2026 and initiate new clinical trials evaluating WVE-007 as an incretin add-on and as post-incretin maintenance in 2026. WVE-007 is an investigational GalNAc-siRNA that utilizes Wave’s best-in-class proprietary oligonucleotide chemistry and the company’s Stereopure interfering Nucleic Acid (SpiNA) next generation siRNA design. WVE-007 is designed to silence INHBE mRNA, an obesity target with strong evidence from human genetics. In preclinical models, INHBE GalNAc-siRNA led to adipocyte shrinkage, fewer pro-inflammatory macrophages, less fibrosis, and improved insulin sensitivity in visceral adipose tissue, supporting potential for metabolic improvement. As an add-on to semaglutide, Wave’s GalNAc-siRNA doubled weight loss in mice and prevented weight regain upon cessation of semaglutide. INLIGHT is an ongoing randomized, placebo-controlled (3:1) clinical trial that includes a Phase 1, single-ascending dose portion in otherwise healthy individuals living with overweight or obesity. This portion is designed to address safety, tolerability, pharmacokinetics, and Activin E target engagement. INLIGHT is currently ongoing at multiple trial sites, including in the US. A Phase 2a portion of INLIGHT evaluating multiple WVE-007 doses in individuals with high BMI and comorbidities is expected to initiate in the second quarter of 2026.