Wave Life Sciences Begins Phase 2a Trial of INHBE siRNA WVE-007 Combined With Tirzepatide in Obesity
核心洞察
Wave Life Sciences has initiated a Phase 2a trial of its GalNAc-siRNA candidate WVE-007 combined with weekly tirzepatide in adults living with obesity (搜索).
The placebo-controlled 3:1 study will test 240 mg and 400 mg doses of WVE-007 in patients with BMI 35-50 kg/m2 and type 2 diabetes (搜索).
Preclinical data presented at ObesityWeek 2025 showed the INHBE siRNA doubled weight loss when combined with a GLP-1 (搜索) versus GLP-1 alone.
Wave Life Sciences has initiated a Phase 2a clinical trial evaluating WVE-007, an investigational GalNAc-siRNA, in combination with tirzepatide in adults living with obesity (搜索). The Cambridge, Massachusetts-based company announced the start of the trial on Sept. 23, 2026.
WVE-007 is designed to silence INHBE, a mechanism Wave describes as differentiated from incretin-based therapies. According to the company, its clinical data to date support a profile of fat loss without muscle loss, favorable safety and tolerability, and once- or twice-yearly dosing.
"This combination trial of WVE-007 with weekly tirzepatide marks an important milestone in our development plan to advance WVE-007 across three distinct obesity (搜索) treatment settings: monotherapy, combination therapy, and as a post-incretin maintenance therapy to prevent weight recurrence," said Christopher Wright, MD, PhD, Chief Medical Officer at Wave Life Sciences.
Wright added that preclinical data and emerging clinical data in the field support the potential for enhanced fat loss and preservation of muscle with WVE-007 compared with incretins alone. "The consequence of muscle loss is particularly important since beyond strength, skeletal muscle also plays an important role in both metabolism and weight maintenance," he said.
Trial Design and Dosing
The placebo-controlled Phase 2a combination trial randomizes participants 3:1 and will evaluate 240 mg and 400 mg doses of WVE-007 alongside weekly tirzepatide. The study enrolls individuals living with obesity (搜索), defined as a BMI of 35-50 kg/m2, and type 2 diabetes (搜索).
The combination study sits within the INLIGHT clinical program, which is assessing WVE-007 both as a monotherapy and in combination with tirzepatide for obesity (搜索) and other cardiometabolic indications, including MASH (搜索). An ongoing Phase 2a monotherapy trial includes multiple assessments over a 12-month period. Wave said those results will inform further development of WVE-007 in obesity as well as in MASH, type 2 diabetes (搜索) and cardiovascular disease.
Preclinical Rationale
Wave previously presented preclinical data at ObesityWeek 2025 showing that its INHBE GalNAc-siRNA combined with a GLP-1 (搜索) doubled weight loss compared with GLP-1 alone. The same data set indicated that WVE-007 has potential for synergistic use with GLP-1s and for curtailing weight regain after GLP-1 treatment is stopped.
Maintenance Setting
Beyond the combination and monotherapy studies, Wave said it remains on track to initiate a clinical trial of WVE-007 as a maintenance therapy intended to preserve weight loss following discontinuation of incretin treatment in the second half of 2026.
WVE-007 is the lead program in Wave's pipeline, which also includes WVE-006 for alpha-1 antitrypsin deficiency (搜索) and WVE-008 (搜索) for PNPLA3 I148M liver disease (搜索), along with clinical programs in Duchenne muscular dystrophy (搜索) and Huntington's disease (搜索). The company's PRISM platform combines RNA medicine modalities, including RNAi (SpiNA) and RNA editing (AIMers).