▎WuXi AppTec Content Team Report

The official website of the Chinese Drug Clinical Trial Registration and Information Disclosure Platform announced,AstraZeneca launched eplontersen in ChinaTransthyretin Amyloid CardiomyopathyPhase 3 Study in Subjects.Public information shows,eplontersenYesAn antisense oligonucleotide (ASO) therapy co-developed by AstraZeneca in a collaboration exceeding $3.5 billion was submitted in the United States this March.Marketing Application，Treatment of hereditary transthyretin (TTR)-mediated amyloidosis polyneuropathy (ATTRv-PN).

Screenshot source:China Drug Clinical Trial Registration and Information Disclosure Platform Official Website

The single-stranded DNA molecules of ASO drugs can lead to mRNA degradation or alter mRNA splicing by binding to specific RNA sequences, thereby achieving the effect of targeting the underlying mechanisms of diseases at the mRNA level to treat diseases.Ionis Pharmaceuticals' LICA technology platform improves the characteristics of ASO drugs in multiple ways by conjugating different small molecules to ASOs., not only allowing them to be administered through various methods, but also enabling delivery to different organs and tissues in the human body.

EplontersenIt adopts Ionis Pharmaceuticals, Inc.An ASO drug developed by Ceuticals using ligand-conjugated antisense oligonucleotide (LICA) technology.In December 2021, AstraZeneca announced a global development and commercialization agreement with Ionis Pharmaceuticals for eplontersen.Agreement。Public information shows,eplontersenASO drugs can beSubstances are coupled with ligand molecules that can bind to specific receptors on the cell surface.It is designed for once-a-month administration, allowing patients to self-administer subcutaneously. By inhibiting the production of TTR protein, it treats hereditary and non-hereditary amyloidosis polyneuropathy.。

According to the official website of the Chinese Drug Clinical Trial Registration and Information Disclosure Platform, this AstraZeneca launch isOne3PeriodRandomized study, the purpose isInChinese Transthyretin Amyloid Cardiomyopathy（ATTR-CM）SubjectTo evaluate the effect of eplontersen on TTR reduction and its long-term safety. The trial initially consists of a 24-week double-blind, placebo-controlled treatment period, followed by an open-label extension phase. The principal investigator is Dr. Shuyang Zhang, Chief Physician at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences.

ATTR-CM isA systemic, progressive, and fatal disease that can lead to progressive heart failure and death within four years after diagnosis.. Due to aging or genetic mutations, patients have resulted inTTRAmyloid Misfolding, and deposit as amyloid fibrils in the myocardium, thereby impairing the normal function of the corresponding organ tissues, and ultimately leading to death.

Except forATTR-CM，eplontersen has also been developed for the treatment ofAmyloid TTR Polyneuropathy (ATTR-PN), and has been inPhase 3 ClinicalThe study met all co-primary endpoints and secondary endpoints. This therapy is currently under FDA review.

References:

[1] Official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved May 10, 2023, from https://www.cde.org.cn/main/xxgk/listpage/2f78f372d351c6851af7431c7710a731