Wave Life Sciences reported interim WVE-007 clinical data from the Phase I portion of its INLIGHT trial, showing that a single 240 mg dose of the INHBE-targeting GalNAc-siRNA produced placebo-adjusted reductions in visceral fat of 14.3% (p<0.05) and waist circumference of 3.3% at six months in 32 individuals with overweight or obesity, according to the company. The data also indicated a placebo-adjusted increase in lean mass of 2.4% and a reduction in body weight of 0.9% over the same period. Wave Life Sciences said WVE-007 was generally safe and well tolerated at doses up to 600 mg, with no treatment discontinuations and no severe or serious treatment-emergent adverse events reported.
In the 240 mg cohort, placebo-adjusted reductions in visceral fat progressed from 7.8% at three months to 14.3% at six months, while total fat mass reduction held steady at approximately 5%. Serum Activin E, the downstream protein product of INHBE, showed dose-dependent suppression sustained through at least seven months, with a mean maximum reduction of up to 88%, the company said. A separate 400 mg cohort of 24 participants showed a 5.0% placebo-adjusted reduction in visceral fat at three months, though this group had lower baseline visceral fat levels; a post-hoc analysis restricted to individuals with baseline visceral fat above 500 grams yielded a 7.8% reduction (p<0.05). All treatment-related adverse events across dose groups were mild, and no changes in lipid profiles or liver function tests were reported.
The INLIGHT trial is a randomized, placebo-controlled (3:1) study evaluating single ascending doses of WVE-007 in otherwise healthy adults with overweight or obesity. The 240 mg cohort had an average BMI of 32 kg/m², lower than populations enrolled in later-stage obesity trials. The company did not disclose formal primary endpoint definitions, and no efficacy endpoints beyond body composition and weight were reported. The data remain interim and are based on a subset of enrolled participants in the Phase I single-ascending dose portion of the trial. Wave said it plans to initiate a Phase IIa multidose portion in individuals with BMI of 35–50 kg/m² and comorbidities in the second quarter of 2026.
WVE-007 is a stereopure siRNA designed to silence INHBE mRNA, reducing Activin E levels and inducing fat breakdown in adipocytes. Wave compared the six-month visceral fat-to-muscle ratio change with WVE-007 (-16.5% from baseline) to that reported with weekly semaglutide 2.4 mg (-12.2% from baseline) in the BELIEVE Phase II trial, though the BELIEVE population had a higher average BMI of 37 kg/m². Cross-trial comparisons are limited by differences in study design, duration, and patient populations.
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