On Sept. 3, Ionis Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has approved ZANVASTRO™ (zilganersen) for the treatment of Alexander disease (AxD) in pediatric and adult patients. ZANVASTRO is the first and only disease modifying treatment for AxD, an ultra-rare, progressive and often fatal neurological disorder that can affect motor, cognitive, autonomic and gastrointestinal function. Until now, treatment of AxD has primarily been limited to managing symptoms. ZANVASTRO is an RNA-targeted medicine designed to address the underlying disease mechanism of AxD by reducing the production of glial fibrillary acidic protein (GFAP). ZANVASTRO 50 mg is administered quarterly as an intrathecal (IT) injection.

AxD affects approximately 1 in 1 to 3 million people worldwide. Initial signs of AxD can present from infancy through adulthood and may vary depending on age of onset. As AxD progresses, symptoms may include progressive motor and cognitive dysfunction, a loss of independence and the inability to control muscles for swallowing, airway protection and purposeful movements. AxD is caused by changes in the GFAP gene that lead to the overproduction and toxic accumulation of GFAP in astrocytes. Over time, dysfunction in astrocytes can damage neurons and myelin, which can lead to symptoms commonly associated with AxD.

The FDA approval was based on positive results from the pivotal study of ZANVASTRO in people living with AxD. The pivotal study met its primary endpoint in individuals ≥ 5 years of age, with ZANVASTRO 50 mg demonstrating statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-Meter Walk Test (10MWT), a commonly used measure of gross motor function in neurologic disease, compared to control at Week 61 (least square mean difference 33.3%, p=0.041). ZANVASTRO also demonstrated improvement in gross motor function in patients 2 to 4 years of age as assessed by the Gross Motor Function Measure-88 (GMFM-88), a well-established motor endpoint, compared to control at Week 61. Secondary and exploratory endpoint results from patient/caregiver- and clinician-reported outcome assessments consistently favored ZANVASTRO.

ZANVASTRO demonstrated a favorable safety and tolerability profile, with most adverse events (AEs) being mild or moderate in severity. Serious treatment-emergent adverse events (TEAEs) occurred less frequently in the ZANVASTRO group compared to control.

Ionis is committed to helping people access the medicines they are prescribed and will offer a full suite of services for people prescribed ZANVASTRO through Ionis Every Step™. As part of Ionis Every Step, patients will have access to a wide range of support and resources including disease state and product education for patients and caregivers, access to a dedicated Patient Education Manager, assistance with the insurance approval process, information on affordability programs and other ongoing services and resources throughout the treatment journey. Visit ZANVASTRO.com for more information.

With the approval of ZANVASTRO, the FDA granted Ionis a Rare Pediatric Disease Priority Review Voucher (PRV), a program designed to incentivize the development of therapies for serious and life-threatening diseases by providing a mechanism to potentially accelerate regulatory review timelines for subsequent applications.

ZANVASTRO will be available in the U.S. in the coming weeks.