▎Reporting by the WuXi AppTec Content Team

Today (November 12), the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced,Leaderna's Class 1 new drug LDR2402 injection has been approved for clinical trials, intended for development in treatment.Primary Hypertension. According to public information from Leaderna, this is aSmall Nucleic Acid Drug Targeting Angiotensinogen (AGT)Existing preclinical studies have shown that this product has the potential to extend the dosing interval in clinical treatment (Once every quarter or half a year) Improve patient compliance and potentially reduce blood pressure variability (BPV) by maintaining 24-hour blood pressure, bringing cardiovascular benefits to hypertensive patients.

Screenshot source:CDE Official Website

Angiotensinogen (AGT)Is the most upstream precursor of the renin-angiotensin-aldosterone system (RAAS),Synthesized and secreted in the liver, it triggers a rise in blood pressure through a series of bio-signaling processes.The role of this target in blood pressure regulation has been confirmed, and the inhibition of AGT has an anti-hypertensive effect.

Public information shows that Leaderna was established in 2022, focusing on core technological innovations and new drug development related to oligonucleotides. It has also built a small nucleic acid new drug pipeline in the fields of metabolism and cardiovascular-cerebrovascular diseases, immunity, and chronic inflammation.

According to the previous press release from Leaderna, LDR2402 InjectionIt is a novel small nucleic acid drug developed based on RNA interference (RNAi) technology for the treatment of hypertension.The siRNA targeting AGT, after being conjugated with N-acetylgalactosamine (GalNAc), specifically binds to the asialoglycoprotein receptor on the surface of hepatocyte membranes, enters the hepatocytes, recognizes and degrades AGT mRNA, thereby inhibiting AGT synthesis and reducing blood pressure.In preclinical animal experiments,LDR2402ShowedStable efficacy after a single dose with the potential to last over six months, demonstrating good safety., has the potential to break traditional hypertension treatment models and become a new generation of hypertension treatment methods.

With the aging population and the prevalence of risk factors such as obesity and unhealthy diet, the prevalence of hypertension is still increasing globally.Currently, there are effective antihypertensive treatment methods in clinical practice, but antihypertensive drugs need to be taken daily. Since hypertension is not easily detectable when symptoms are not severe, patients may forget to take their medication, and poor compliance has become a major challenge in the current treatment of hypertension.Therefore, the development of a long-acting antihypertensive drug with reliable efficacy and significant improvement in patient medication adherence holds urgent clinical value.

Targeting the treatment bottleneck of hypertension, siRNA drugs can directly reduce the expression of AGT.With differentiated advantages such as long-lasting drug efficacy, good safety, and high patient compliance.`, which is expected to bring better treatment options and long-term benefits to patients. This type of drug has also attracted multiple companies to invest in research and development. In addition to the recent approval for clinical trials,`LDR2402 InjectionRNAi therapy jointly developed by Alnylam Pharmaceuticals and RochezilebesiranPositive results have already been achieved in Phase 2 clinical trials, with some patients who received a single injection of the product still maintaining a sustained reduction in blood pressure at the 6-month follow-up.The small nucleic acid (siRNA) drug for treating hypertension co-developed by Leaderna and Innovent BiologicsSGB-3908The injection has currently entered Phase 1 clinical research stage;Leaderna's GalNAc-siRNA molecules under researchR0797070The preclinical study results have been published previously.

References:

[1] Official Website of the Center for Drug Evaluation, National Medical Products Administration of ChinaWebsite. Retrieved Nov 12, 2024, from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c

[2]Leadena's IND Application for Ultra-Long-Acting Small Nucleic Acid Drug for Hypertension Treatment Accepted. Retrieved Aug 30, 2024, from https://mp.weixin.qq.com/s/PndG8xBZMQ7k9kyh_K1E1Q