お知らせ • Apr 22
Ionis Pharmaceuticals Inc Presents New Data from Pivotal Study of Zilganersen in Alexander Disease
Ionis Pharmaceuticals, Inc. announced additional positive results from the pivotal study of zilganersen in children and adults living with Alexander disease (AxD), a rare, progressive and often fatal neurological condition with no approved disease-modifying treatments. These findings, which will be presented at the 2026 American Academy of Neurology (AAN) annual meeting, build on previously reported positive topline data and provide a more comprehensive view of treatment effect across multiple clinically meaningful domains. The study met its primary endpoint in individuals =5 years of age, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-Meter Walk Test (10MWT), compared to control at Week 61. The 10MWT is a commonly used measure of gross motor function in neurologic disease. New data from the Gross Motor Function Measure-88 (GMFM-88), a well-established motor endpoint, supports the primary outcome of the study by demonstrating that treatment with zilganersen may improve gross motor function in younger children (2-4 years of age), compared to control. Key secondary endpoint results from patient/caregiver- and clinician-reported outcome assessments consistently favored zilganersen. Zilganersen demonstrated favorable safety and tolerability. AxD is a rare, genetic, progressive and often fatal neurological condition that is primarily associated with toxic over-production of glial fibrillary acidic protein (GFAP). It is estimated to occur in approximately 1 per 1 to 3 million people worldwide. Although symptoms vary depending on age of onset, individuals may experience progressive motor and cognitive dysfunction, a loss of independence and the inability to control muscles for swallowing, airway protection and purposeful movements. Zilganersen is an investigational RNA-targeted medicine designed to reduce overproduction of GFAP, the underlying cause of AxD. The pivotal Phase 1-3 study of zilganersen included 53 people with AxD aged 2 to 53 years. Results presented are from the 60-week double-blind, randomized controlled treatment period of the ongoing trial. Zilganersen met the primary endpoint in patients =5 years, resulting in statistically significant and clinically meaningful stabilization of gait speed on the 10MWT at Week 61 compared to control (least square mean difference 33.3%, p=0.041). Additionally, results from the GMFM-88 in children 2-4 years of age support that zilganersen may improve gross motor function at Week 61 compared to control (least square mean difference 22.9 points, nominal1 p=0.034). Key secondary endpoints favored zilganersen over control: Key secondary endpoints evaluated the disease’s heterogeneous presentation through assessments focused on the individual’s most bothersome AxD symptom and their overall health. Across these measures, outcomes favored zilganersen-treated individuals, with more reporting improvement or no change and fewer reporting worsening compared to control. Most Bothersome Symptom (MBS): In the zilganersen group, 32% of patients rated their most bothersome symptom as “much better” compared to 0% on control. Only 5% of patients receiving zilganersen rated their most bothersome symptom as “much worse” compared to 31% on control. Patient Global Impression of Severity (PGIS): In the zilganersen group, 83% of patients reported improvement or no change in overall disease severity compared to 76% on control. Only 17% of patients receiving zilganersen reported worsening compared to 24% on control. Patient Global Impression of Change (PGIC): In the zilganersen group, 21% of patients reported feeling “much better” overall compared to 0% on control. Only 4% of patients receiving zilganersen reported feeling “much worse” compared to 18% on control. Clinical Global Impression of Change (CGIC): Clinicians rated 75% of patients receiving zilganersen as improved (“a little better”) or “no change” compared to 47% on control. Clinicians rated 25% of patients receiving zilganersen as “a little worse” and 0% as “much worse” compared to 41% as “a little worse” and 12% as “much worse” on control. Results from additional secondary and exploratory endpoints assessing communication, swallowing, gastrointestinal and autonomic symptoms, consistently support that zilganersen may have a positive impact across AxD symptoms. In an exploratory analysis, zilganersen reduced plasma GFAP levels by 33.6% at Week 61 compared to control (nominal1 p=0.003)2, consistent with its mechanism of targeting GFAP RNA in the central nervous system. Zilganersen demonstrated a favorable safety and tolerability profile, with most adverse events (AE) mild or moderate in severity. Serious treatment-emergent adverse events (TEAEs) occurred less frequently in the zilganersen group compared to control (37.5% zilganersen 25 mg or 50 mg; 47.1% pooled control). Zilganersen is currently under Priority Review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) action date of September 22, 2026. The global, multicenter, randomized, double-blind, controlled, multiple-ascending dose (MAD) Phase 1-3 study (NCT04849741) enrolled 54 participants with Alexander disease (AxD) between the ages of 1.5 and 53 years across 13 sites in eight countries. Most participants in the study were children, reflecting the early onset and severe progression of AxD in pediatric populations. Participants were randomized in a 2:1 ratio to receive zilganersen or control for a 60-week double-blind treatment period. The study included two dose cohorts, 25 mg and 50 mg, with the 50 mg dose cohort analyzed as the pivotal dose cohort, with dosing every 12 weeks. At 60 weeks, all eligible participants transitioned into an open-label treatment period, followed by a 120-week open-label, long-term extension treatment period, during which participants in the 25 mg dose cohort moved to the 50 mg dose cohort, and finally a 28-week post-treatment follow-up period. The primary endpoint is percent change from baseline in gait speed as assessed by the 10-Meter Walk Test (10MWT), an assessment of functional mobility, at the end of the double-blind treatment period. Key secondary endpoints include patients' self-identified Most Bothersome Symptom (MBS) Score, change from baseline in Patient Global Impression of Severity (PGIS) Score and Patient Global Impression of Change (PGIC) Score and Clinician Global Impression of Change (CGIC) Score at the end of the double-blind treatment period. Zilganersen is an investigational RNA-targeted medicine being evaluated as a treatment for people with Alexander disease (AxD).