FDA approves first disease modifying treatment for Alexander disease
The US Food and Drug Administration (FDA) has approved Ionis Pharmaceuticals’ Zanvastro (zilganersen) for the treatment of Alexander disease (AxD) in paediatric and adult patients.
It 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.
AxD is caused by changes in the glial fibrillary acidic protein (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.
Zanvastro is an RNA-targeted medicine designed to address the underlying disease mechanism of AxD by reducing the production of GFAP.
“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 Monia, Chief Executive Officer, 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.”
Addressing underlying biology of AxD
In a pivotal study, Zanvastro met its primary endpoint in individuals ≥5 years of age, with a 50mg dose 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 6.
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 (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 favoured Zanvastro.
“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,” said Dr Amy Waldman, Paediatric Neurologist and lead investigator for the Zanvastro study at Children’s Hospital of Philadelphia. “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.”