速递｜不靠少吃多动，靠关基因：Arrowhead 把减肥战场推进到脂肪源头

Core Viewpoint - Arrowhead Pharmaceuticals is targeting the obesity market with two gene-silencing candidates showing potential for fat reduction rather than just weight loss, leading to a significant stock price increase after the announcement [5][8]. Group 1: Clinical Data and Mechanisms - Arrowhead disclosed early clinical data for two assets with different mechanisms: one targeting liver INHBE gene expression and the other targeting ACVR1C gene in adipocytes [5]. - In a small exploratory study, participants with obesity and type 2 diabetes showed an average weight loss of 9.4% after 16 weeks of treatment with ARO-INHBE combined with tirzepatide, compared to 4.8% in the control group using tirzepatide plus placebo [6]. - The combination therapy also resulted in reductions in visceral fat, total fat, and liver fat content, although Arrowhead did not disclose data on ARO-INHBE as a monotherapy [6][8]. Group 2: Industry Insights and Regulatory Changes - The industry consensus suggests that such molecules are more likely to serve as enhancers of GLP-1 drugs rather than standalone weight loss medications [7]. - Regulatory pathways are evolving, with the FDA potentially accepting "additional quantifiable fat reduction effects on top of GLP-1" as a primary endpoint, shifting focus from mere weight loss to fat distribution and muscle preservation [7]. - Arrowhead's ACVR1C-targeting asset, ARO-ALK7, showed an 88% average reduction in ALK7 mRNA in adipose tissue at a 200 mg dose, with a 14.1% average reduction in visceral fat after 8 weeks [7]. Group 3: Market Reaction and Future Outlook - The market reacted positively, with Arrowhead's stock rising approximately 17% to $75, indicating investor confidence in the potential of next-generation obesity treatments that may focus on deeper metabolic regulation rather than solely on incretin-based therapies [8].