Wave Life Sciences has submitted its first clinical trial application (CTA) for WVE-007 in obesity. WVE-007 is an investigational GalNAc-conjugated small interfering RNA (siRNA) designed to silence Inhibin βE (INHBE) gene expression, which would induce fat burning (lipolysis) to decrease body weight without impacting muscle mass. Wave expects CTA approval and initiation of the first-in-human study of WVE-007 in the first quarter of 2025.
“Our WVE-007 programme, which uses Wave’s best-in-class GalNAc-siRNA capabilities with proprietary chemistry, has potential to be dosed once or twice annually and may ultimately be used across the obesity treatment continuum for sustainable weight loss and cardiometabolic risk reduction,” said Dr Paul Bolno, President and Chief Executive Officer at Wave Life Sciences. “With a growing understanding of human genetics and opportunities to directly impact adipose tissue, INHBE has emerged as an exciting, novel therapeutic target to address obesity, without the challenges of current standard-of-care therapeutics.”
Human genetics provide strong evidence for INHBE as a therapeutic target. Individuals who have a protective loss-of-function mutation in the INHBE gene have a healthier cardiometabolic profile, including less abdominal fat, lower triglycerides, and lower risk of type 2 diabetes and cardiovascular disease. WVE-007 is designed to induce this healthy phenotype through INHBE gene silencing, leading to fat burning and improvements in metabolic health.
In preclinical studies using a mouse model of diet induced obesity (DIO), a single dose of Wave’s INHBE siRNA led to weight loss on par with semaglutide, with no muscle loss. When administered as an add-on to semaglutide, a single dose doubled the amount of weight loss. In another study, Wave’s INHBE siRNA also prevented weight regain when semaglutide treatment was discontinued.
Wave’s first-in-human study of WVE-007 is a Phase 1 clinical trial in adults living with overweight or obesity. The trial is designed to assess safety, tolerability, pharmacokinetics, and biomarkers for target engagement, as well as body composition and metabolic health.
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