CARLSBAD, Calif., July 18, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that it has completed enrollment in the pivotal trial of zilganersen (ION373), an investigational RNA-targeted medicine in development for the treatment of children and adults with a rare, progressive and ultimately fatal neurological disorder known as Alexander disease (AxD).

加利福尼亚州卡尔斯巴德，2024年7月18日/PRNewswire/--Ionis Pharmaceuticals，Inc.（纳斯达克：IONS）今天宣布，它已经完成了zilganersen（ION373）关键试验的注册，zilganersen（ION373）是一种研究性RNA靶向药物，正在开发中，用于治疗儿童和成人罕见的，进行性的，最终致命的神经系统疾病，称为亚历山大病（AxD）。

The primary endpoint is percent change from baseline in gait speed as assessed by the 10-Meter Walk Test (10MWT). Topline data are anticipated in the second half of 2025..

主要终点是通过10米步行测试（10MWT）评估的步态速度与基线的百分比变化。预计2025年下半年将公布顶线数据。。

AxD is estimated to occur in an estimated one in one million people in the U.S. and can present throughout life.1-3 The disease is a result of genetic variants in the glial fibrillary acidic protein (GFAP) gene that disrupt the structure and function of astrocytes in the brain. AxD is generally characterized by cognitive dysfunction and progressive neurologic deterioration, including loss of independence and the ability to control muscles for large movements, swallowing and airway protection.

据估计，在美国，每百万人中就有一人患有AxD，并可能终生存在。1-3该疾病是神经胶质纤维酸性蛋白（GFAP）基因遗传变异的结果，该基因破坏了大脑中星形胶质细胞的结构和功能。AxD通常以认知功能障碍和进行性神经系统恶化为特征，包括丧失独立性和控制肌肉进行大运动，吞咽和气道保护的能力。

Zilganersen is designed to stop the excess GFAP that accumulates because of disease-causing variants in the GFAP gene, with the goal of slowing or stabilizing disease progression in people living with AxD..

Zilganersen旨在阻止由于GFAP基因致病变异而积累的过量GFAP，目的是减缓或稳定AxD患者的疾病进展。。

'Current approaches to disease management for Alexander disease can mitigate some symptoms of AxD but do not address the underlying cause or slow disease progression. Our zilganersen study is the first trial to evaluate an investigational medicine designed to address the underlying cause of Alexander disease,' said Eugene Schneider, M.D., executive vice president and chief clinical development officer at Ionis.

“目前针对亚历山大病的疾病管理方法可以缓解AxD的某些症状，但不能解决根本原因或减缓疾病进展。尤金·施耐德（EugeneSchneiderM.）说，我们的齐尔加内森（zilganersen）研究是第一个评估旨在解决亚历山大病根本原因的研究药物的试验。D、 ，Ionis执行副总裁兼首席临床开发官。

'We are grateful for the dedication and support from the patients, families and investigators in the Alexander disease community, whose partnership has made this milestone possible.'.

“我们感谢亚历山大疾病社区的患者，家属和研究人员的奉献和支持，他们的合作使这一里程碑成为可能。”。

About the Zilganersen Study The global, multicenter, randomized, double-blind, controlled, multiple-ascending dose (MAD) is a Phase 1-3 study (NCT04849741), which enrolled patients aged two to 65 with Alexander disease (AxD) across 13 sites in eight countries. Participants were randomized in a 2:1 ratio to receive zilganersen or control for a 60-week double-blind treatment period.

关于Zilganersen研究，全球多中心，随机，双盲，对照，多次递增剂量（MAD）是一项1-3期研究（NCT04849741），该研究招募了8个国家13个地点的2至65岁亚历山大病（AxD）患者。。

At 60 weeks, all participants will receive zilganersen for a 180-week open-label treatment period, followed by a 28-week post-treatment follow-up period. The primary endpoint is percent change from baseline in gait speed as assessed by the 10-Meter Walk Test (10MWT) at the end of the double-blind treatment period.

在60周时，所有参与者将接受为期180周的开放标签治疗期，然后是28周的治疗后随访期。。

Secondary endpoints include change from baseline in patients' self-identified Most Bothersome Symptom (MBS) Score, Patient Global Impression of Severity (PGIS) Score, Patient Global Impression of Change (PGIC) Score and Clinician Global Impression of Change (CGIC) Score at the end of the double-blind treatment period..

次要终点包括患者自我识别的最烦人症状（MBS）评分，患者总体严重程度印象（PGIS）评分，患者总体变化印象（PGIC）评分和临床医生总体变化印象（CGIC）评分在双盲治疗期结束时的基线变化。。

The study includes an open-label sub-study in eligible participants under the age of two years with AxD, which will continue to enroll into 2025.

该研究包括一项针对两岁以下符合条件的AxD参与者的开放标签子研究，该研究将继续注册到2025年。

About Zilganersen (ION373)Zilganersen is an investigational antisense oligonucleotide medicine being developed as a potential treatment for people with genetically confirmed Alexander disease (AxD). Zilganersen is designed to stop the excess glial fibrillary acidic protein (GFAP) production that accumulates because of disease-causing variants in the GFAP gene.

关于Zilganersen（ION373）Zilganersen是一种研究性反义寡核苷酸药物，正在开发中，作为遗传证实的亚历山大病（AxD）患者的潜在治疗方法。Zilganersen旨在阻止由于GFAP基因的致病变异而积累的过量胶质纤维酸性蛋白（GFAP）的产生。

In 2020, the U.S. Food and Drug Administration (FDA) granted zilganersen Orphan Drug designation and Rare Pediatric designation. In addition, the European Medicines Agency (EMA) granted zilganersen Orphan Drug designation in 2019..

2020年，美国食品和药物管理局（FDA）批准了齐尔加内森孤儿药和罕见儿科药物。此外，欧洲药品管理局（EMA）于2019年授予齐尔加内森孤儿药称号。。

About Alexander Disease (AxD)AxD is a rare, progressive and ultimately fatal neurological disease that affects a type of cell in the brain called astrocytes. Astrocytes have multiple roles in the brain to support neurons and oligodendrocytes, including maintenance of the myelin sheath that protects nerve fibers.

关于亚历山大病（AxD）AxD是一种罕见的，进行性的，最终致命的神经系统疾病，会影响大脑中一种称为星形胶质细胞的细胞。星形胶质细胞在大脑中有多种作用来支持神经元和少突胶质细胞，包括维持保护神经纤维的髓鞘。

AxD is caused by disease-causing variants in the glial fibrillary acidic protein (GFAP) gene and is generally characterized by cognitive dysfunction and progressive neurologic deterioration, including loss of independence and the ability to control muscles for large movements, swallowing and airway protection, though symptoms can vary depending on age of onset.

AxD是由胶质纤维酸性蛋白（GFAP）基因的致病变异引起的，通常以认知功能障碍和进行性神经功能恶化为特征，包括丧失独立性和控制肌肉进行大运动，吞咽和气道保护的能力，尽管症状可能因发病年龄而异。

AxD usually leads to death within 14-25 years after symptom onset. There are no disease modifying medicines approved for patients..

AxD通常在症状出现后14-25年内导致死亡。没有批准用于患者的疾病缓解药物。。

About Ionis Pharmaceuticals, Inc.For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing.

关于Ionis Pharmaceuticals，Inc.三十年来，Ionis发明了为严重疾病患者带来更好未来的药物。Ionis目前拥有五种上市药物，并在神经病学、心脏病学和其他患者需求较高的领域拥有领先的渠道。作为RNA靶向药物的先驱，Ionis除了推进基因编辑的新方法外，还继续推动RNA疗法的创新。

A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients..

对疾病生物学和业界领先技术的深入了解推动了我们的工作，同时也激发了我们为患者带来改变生活的进步的热情和紧迫感。。