Ionis Pharmaceuticals Wins FDA Approval for First Alexander Disease Treatment

Ionis Pharmaceuticals received FDA approval for ZANVASTRO, the first disease-modifying treatment for Alexander disease, with a broad label covering children and adults.

The approval was supported by a 54-patient trial showing statistically significant stabilization of gait, improvements in motor function among younger children, and reductions in plasma GFAP; most adverse reactions were mild to moderate.

Ionis priced ZANVASTRO at $285,000 per quarterly dose and expects peak sales above $100 million, while focusing its U.S. launch on specialized treatment centers, patient identification and payer reimbursement.

Ionis Pharmaceuticals NASDAQ: IONS said the U.S. Food and Drug Administration has approved ZANVASTRO as the first and only disease-modifying treatment for Alexander disease, an ultra-rare, progressive neurological disorder caused by pathogenic variants in the GFAP gene.

The approval includes a broad label for children and adults with Alexander disease and arrived nearly three weeks ahead of the anticipated FDA decision date, according to Chief Executive Officer Brett Monia.

The company said ZANVASTRO will be its first independently commercialized neurology launch.

Alexander disease affects the brain’s white matter and can cause progressive motor and cognitive dysfunction, loss of mobility and independence, and difficulty with swallowing, airway protection and purposeful movement.

Symptoms commonly begin in infancy or childhood but can emerge at any age.

The disease is estimated to affect roughly one in 1 million to 3 million people worldwide and is almost always fatal, Chief Development Officer Holly Kordasiewicz said.

The FDA approval was based on a controlled, integrated trial that combined first-in-human dose finding and pivotal-study components.

The study enrolled 54 patients between ages 2 and 53, with most participants younger than 18 at enrollment.

The pivotal portion evaluated a 50-milligram quarterly intrathecal dose of ZANVASTRO.

The primary endpoint assessed stabilization of gait speed in patients age 5 and older through the 10-meter walk test.

Ionis said the study met that endpoint, demonstrating a statistically significant and clinically meaningful stabilization of gait among patients receiving the 50-milligram dose.

Secondary and exploratory measures also favored ZANVASTRO, according to the company.

In patients ages 2 to 4, the drug improved gross motor function versus control on the Gross Motor Function Measure-88.

ZANVASTRO also reduced plasma GFAP compared with control, which Ionis said provided evidence of target engagement and modulation of the disease’s underlying mechanism.

The company reported that most adverse reactions were mild to moderate, while serious adverse reactions occurred less frequently with ZANVASTRO than with control.

Kordasiewicz said the safety profile was broadly similar between pediatric and adult patients.

ZANVASTRO is administered through intrathecal injection once every quarter.

Ionis initially tested a lower 25-milligram quarterly dose in a small patient group to establish safety and pharmacokinetics before evaluating the approved 50-milligram regimen in a larger cohort.

Ionis estimates that about 300 people in the U.S. are living with Alexander disease, with approximately half identified through medical claims.

Many patients receiving supportive care are treated at about 12 leukodystrophy Centers.