Ionis Pharmaceuticals has announced that the US 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.

Brett P Monia, PhD, Chief Executive Officer (CEO), Ionis Pharmaceuticals, said, “Today’s approval of ZANVASTRO begins a new chapter for people living with Alexander Disease and their families, who have long faced this relentlessly progressive and often fatal disease with no treatment options. This transformative approval also marks our first independent launch from our industry-leading neurology pipeline and underscores the power of our RNA-targeted technology to address serious neurological diseases without adequate treatment options. We are proud to bring this important new treatment to this incredible community and are deeply grateful to the clinical trial participants and their families, regulators, investigators and advocates who helped make this advancement possible.”

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.

Amy Waldman, MD, MSCE, pediatric neurologist and lead investigator for the ZANVASTRO study at Children’s Hospital of Philadelphia, said, “For decades, care for people living with Alexander Disease has focused primarily on managing symptoms, without an option to modify the underlying cause of disease. The approval of ZANVASTRO for the treatment of Alexander Disease represents a significant advancement in care and opens new possibilities for patients and their families. For the first time, we can move beyond managing individual manifestations of the disease to addressing its underlying biology, with the potential to meaningfully improve outcomes for this community.”

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 stabilisation 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 percent, 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. It also 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.

With the approval of ZANVASTRO, the FDA granted Ionis a rare pediatric disease Priority Review Voucher (PRV), a program designed to incentivise 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 US in the coming weeks.

In June 2026, Ionis entered into a license agreement with Recordati, a global pharmaceutical company headquartered in Italy, focused on specialty and rare diseases, under which Recordati obtained exclusive rights to develop and commercialise zilganersen in all countries outside the US. Ionis is working closely with Recordati on preparing regulatory submissions in Europe and Japan, which are expected in 2027.