FDA approved Zanvastro (zilganersen) for the treatment of Alexander disease in pediatric and adult patients.

Zanvastro is the first and only disease-modifying treatment for Alexander disease, an ultra-rare, progressive and often fatal neurological disorder that can affect motor, cognitive, autonomic and gastrointestinal function; until now, treatment has primarily been limited to managing symptoms.¹

Zanvastro is an RNA-targeted medicine designed to address the underlying disease mechanism of Alexander disease by reducing the production of glial fibrillary acidic protein, or GFAP.¹ Zanvastro 50 mg is administered quarterly as an intrathecal injection.

What is the approval based on?

FDA's approval was based on positive results from the pivotal study of Zanvastro in people living with Alexander disease.^1,2 The study met its primary endpoint in individuals 5 years of age and older, with Zanvastro 50 mg demonstrating statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-Meter Walk Test compared with control at Week 61, with a least square mean difference of 33.3% (p=0.041).¹ Zanvastro also demonstrated improvement in gross motor function in patients two to four years of age as assessed by the Gross Motor Function Measure-88, a well-established motor endpoint, compared with control at Week 61.¹

In the trial, secondary and exploratory endpoint results from patient, caregiver, and clinician-reported outcome assessments consistently favored Zanvastro, as the drug demonstrated a favorable safety and tolerability profile as most adverse events were recorded as mild or moderate in severity, and serious treatment-emergent adverse events occurring less frequently in the Zanvastro group compared with control.¹

"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," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "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."

What is Alexander disease?

Alexander disease affects approximately one in one to three million people worldwide. Initial signs can present from infancy through adulthood and may vary depending on age of onset.¹ As the disease 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.¹ Alexander disease 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 the symptoms commonly associated with the disease.

"As a mom to a young boy living with Alexander disease and an advocate for this community, I have seen firsthand the profound impact this disease has on individuals and their families. Today's approval represents a fundamental shift, changing the conversation from 'How do we manage this disease' to 'How can we treat it,'" said Emily Petty, president of End Alexander Disease. "For far too long, receiving a diagnosis of Alexander disease was accompanied by uncertainty and the difficult reality that there were no available treatments. Today, that begins to change. Zanvastro marks a defining moment and brings a new sense of possibility to our community."

What's next for the drug?

Along with the approval, FDA granted Ionis a Rare Pediatric Disease Priority Review Voucher, a program designed to incentivize development of therapies for serious and life-threatening diseases. Zanvastro is expected to be available in the U.S. in the coming weeks, and Ionis will offer a full suite of patient support services through its Ionis Every Step program, including disease state and product education, a dedicated Patient Education Manager, help with insurance approval, and information on affordability programs.^1,2

“What we've really seen over the last couple of years is a commitment to developing therapies for rare diseases, evidenced by the formation of a rare disease review division within the centers at CBER, as well as some additional offices like the Rare Disease Hub and Rare Disease representation within the Office of the Commissioner," said Lisa Bollinger, chief medical officer at Polaryx, in an interview with Pharmaceutical Executive.

Ionis has already lined up its path beyond the U.S. market. Back in June 2026, the company 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 commercialize zilganersen in all countries outside the U.S.

Sources

1. Zanvastro (zilganersen) approved by the FDA as the first and only disease modifying treatment for Alexander disease (AxD) in pediatric and adult patients Ionis Pharmaceuticals Septmber 3, 2026, https://ir.ionis.com/news-releases/news-release-details/zanvastrotm-zilganersen-approved-fda-first-and-only-disease
2. Ionis Pharma's drug becomes first FDA-approved treatment for rare brain disorder Reuters September 3, 2026, https://www.reuters.com/legal/litigation/us-fda-approves-ionis-pharmas-therapy-treat-rare-brain-disorder-2026-09-03/