Wave Life Sciences has announced clinical trial application (CTA) approval and initiation of the Phase 1 INLIGHT clinical trial of WVE-007 in obesity. WVE-007 is a long-acting GalNAc-conjugated small interfering RNA (siRNA) that targets INHBE messenger RNA. INHBE mRNA encodes a protein called Activin E that is secreted from the liver and acts directly on fat cells to block fat burning (“lipolysis”); therefore, silencing of INHBE would restart and maintain lipolysis. Human genetics also provide strong evidence for INHBE as a therapeutic target.
Individuals who have a protective loss-of-function mutation in one copy of 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, leading to fat burning, muscle preservation, and improvements in metabolic health. Preclinical data using a mouse model of diet induced obesity (DIO) demonstrate WVE-007’s potential in multiple treatment settings, including as a monotherapy, as an add-on to GLP-1s, and as a maintenance treatment to prevent weight regain upon discontinuation of GLP-1 treatment.
INLIGHT is a Phase 1, first-in-human clinical trial, which is designed to enrol adults living with overweight or obesity and assess safety, tolerability, pharmacokinetics, biomarkers for target engagement, body weight and composition, and metabolic health. Assessments of healthy weight loss, or fat loss with lean mass preservation, are consistent with recently issued FDA draft guidance on developing therapeutics for weight reduction.
“WVE-007 is designed to treat obesity in an entirely new way by directly impacting fat cells to drive weight reduction, maintain muscle mass, and improve cardiometabolic health outcomes. With the potential for once- or twice-yearly dosing, WVE-007 is uniquely positioned to address more than 1 billion people living with obesity globally,” said Dr Paul Bolno, President and Chief Executive Officer at Wave Life Sciences. “WVE-007 is also Wave’s first siRNA to enter clinical development and utilises our state-of-the art chemistry delivering potentially best-in-class silencing and durability. We are excited to continue advancing WVE-007 as we enter a new era for RNA interference and its application in common diseases.”
Proof-of-concept clinical data from INLIGHT, including safety, tolerability, and biomarkers reflective of healthy weight loss, are expected in 2025.
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