Wave Life Sciences (NASDAQ:WVE) saw its shares fall more than 52% following the release of six-month Phase 1 data for WVE-007, its investigational INHBE GalNAc-siRNA therapy, despite results showing improvements in body composition and continued safety and tolerability.
The Phase 1 INLIGHT trial reported that a single 240 mg dose of WVE-007 produced placebo-adjusted reductions of 14.3% in visceral fat, 5% in total fat, a 2% increase in lean mass, a 3.3% reduction in waist circumference, and a 0.9% reduction in body weight after six months.
At three months, the same cohort had shown 7.8% visceral fat reduction, 0.3% body weight loss, and a 0.4% decrease in waist circumference.
The study also demonstrated durable suppression of serum Activin E for at least seven months, supporting the potential for once- or twice-yearly dosing.
Wave’s Phase 1 cohort included 32 participants with an average BMI of 32 kg/m². The company noted that the improvements in body composition occurred in participants with lower baseline BMI and fat levels than those typically enrolled in later-stage obesity trials.
“WVE-007 is already translating in the clinic with potent and durable Activin E reductions and it continues to be safe and well tolerated,” Wave Life Sciences’ chief medical officer Dr Christopher Wright said.
“Even in this early Phase 1 trial, we are seeing our differentiated chemistry translate into clinically meaningful levels of fat loss, particularly harmful visceral fat, with muscle preservation.”
Wave plans to begin the Phase 2a multidose portion of INLIGHT in the second quarter of 2026. This study will test WVE-007 as a monotherapy in individuals with BMIs of 35–50 and additional comorbidities, with company scientists anticipating larger reductions in body weight and fat in this higher-BMI population.