Ionis Pharmaceuticals has won US FDA approval for ZANVASTRO, offering patients with Alexander disease (AxD), a rare and often fatal neurological disease, a treatment aimed at its underlying cause.

 

The company said ZANVASTRO (zilganersen) is designed to reduce production of glial fibrillary acidic protein (GFAP), whose toxic accumulation in brain cells called astrocytes drives the disease. The treatment is administered as a 50 mg intrathecal injection every 12 weeks.

 

Until now, treatment for AxD has largely focused on managing symptoms rather than slowing the underlying disease process.

 

“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, 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. 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 roughly one in 1 million to 3 million people worldwide. The disease can emerge from infancy through adulthood and progressively impair motor and cognitive function, independence, swallowing, airway protection and purposeful movement. It is caused by disease-causing changes in the GFAP gene that result in excessive production and toxic accumulation of GFAP in astrocytes.

 

The FDA's decision was supported by results from a pivotal clinical study involving 54 participants between 1.5 and 53 years old across 13 sites in eight countries.

 

Among participants aged 5 and older, ZANVASTRO met the study's primary endpoint, showing statistically significant and clinically meaningful stabilization of gait speed compared with control at Week 61. The company reported a least-square mean difference of 33.3% on the 10-Meter Walk Test, with a p-value of 0.041.

 

The treatment also improved gross motor function among children aged 2 to 4, based on the Gross Motor Function Measure-88. Patient-, caregiver- and clinician-reported measures consistently favored ZANVASTRO, according to Ionis.

 

“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 Amy Waldman, pediatric 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.”

 

Safety results were described as favorable, with most adverse events reported as mild or moderate. Serious treatment-emergent adverse events occurred less frequently in the ZANVASTRO group than in the control group.

 

The most common adverse reactions occurring in at least 25% of patients treated with ZANVASTRO and at a higher rate than control were vomiting, back pain, cough, headache and post-lumbar puncture syndrome. The prescribing information also carries a warning for aseptic meningitis.