Arrowhead Pharmaceuticals Unveils Obesity Treatment at ADA Conference
Arrowhead Pharmaceuticals Unveils Obesity Treatment at ADA Conference
Arrowhead Pharmaceuticals, Inc. (NASDAQ:ARWR) today announced that preclinical data on ARO-INHBE, an investigational RNAi-based medicine for the treatment of obesity and metabolic diseases, were presented at the American Diabetes Association (ADA) 84th Scientific Sessions, which were held June 21-24, in Orlando, FL, and virtually.
纳斯达克上市公司Arrowhead Pharmaceuticals, Inc. (NASDAQ：ARWR)今日宣布其针对肥胖和代谢性疾病的干扰RNA药物候选药ARO-INHBE的临床前数据已在美国糖尿病协会（ADA）第84届科学会议上（6月21日至24日，于佛罗里达州奥兰多市及虚拟）公布。
The preclinical results demonstrate that ARO-INHBE substantially silenced hepatic expression of the INHBE gene, which has been identified through large genetic studies as a promising target for next generation therapies to address obesity and metabolic diseases. Further, Arrowhead's preclinical research suggests that INHBE knockdown may potentially lead to a suppression in body weight gain, loss of fat mass, and preservation of lean mass. Arrowhead plans to file for regulatory clearance in late 2024 to begin clinical studies of ARO-INHBE.
临床前结果表明，ARO-INHBE明显抑制了肝脏中INHBE基因的表达，该基因经过大规模的遗传研究被确定为下一代治疗肥胖和代谢性疾病的有望靶点。此外，Arrowhead的临床前研究表明，INHBE的抑制可能潜在地导致体重增加的抑制、脂肪质量的减少和瘦体重的保持。Arrowhead计划于2024年底申请监管机构批准，开始ARO-INHBE的临床研究。
"There has been a great deal of progress with new agents to treat obesity and metabolic diseases, but significant loss of lean mass and adverse gastrointestinal events at higher dose levels have necessitated the identification of new therapeutic strategies with novel mechanisms of action," said James Hamilton, M.D., chief of discovery and translational medicine at Arrowhead. "ARO-INHBE directly targets hepatic expression of the INHBE gene. Prior genetic studies have associated loss of function mutations in the INHBE gene with reduced levels of abdominal fat and an improved metabolic profile. Our preclinical data presented at ADA suggest that INHBE reduction with siRNA is a promising new approach to address obesity and metabolic diseases and strongly support advancing ARO-INHBE into clinical trials."
"虽然新药物治疗肥胖和代谢性疾病取得了很大的进展，但在更高剂量下损失大量瘦体重和出现不良的肠胃事件，必须寻找新的治疗策略和新的作用机制。"Arrowhead的发现和转化医学首席医生James Hamilton博士说:"ARO-INHBE直接靶向肝脏中的INHBE基因表达。以往的遗传研究表明INHBE基因缺陷与腹部脂肪的减少和改善代谢水平有关。我们在ADA上展示的临床前数据表明，使用siRNA减少INHBE表达是解决肥胖和代谢性疾病的有前途的新方法，并且强烈支持将ARO-INHBE推进临床试验。"
In pharmacological studies in obese and diabetic mouse models, INHBE siRNA administration resulted in multiple promising findings, including the following:
在肥胖和糖尿病小鼠模型中的药理研究中，INHBE siRNA的使用带来了多种有望的发现，包括以下内容：
- 95% reduction in INHBE mRNA expression
- 19% suppression of body weight compared to saline controls
- 26% loss of fat mass
- Preservation of lean mass
- INHBE mRNA表达量的减少达到了95%。
- 与盐水对照组相比，体重减轻了19%。
- 脂肪质量减少了26%。
- 瘦体重得到了保持。
In addition, co-treatment of tirzepatide with INHBE siRNA allowed for the use of a lower tirzepatide dose without compromising its therapeutic effect. These encouraging results suggest that ARO-INHBE has the potential to be a novel therapeutic for metabolic disease.
此外，联合使用tirzepatide和INHBE siRNA可在不损害其治疗效果的情况下使用更低剂量的tirzepatide。这些令人鼓舞的结果表明，ARO-INHBE有望成为代谢性疾病的新型治疗药物。