Ionis Pharmaceuticals Reports Positive Phase III Results for Zilganersen in Alexander Disease

Ionis Pharmaceuticals (IONS) announced positive phase III study results for its investigational RNA-targeted therapy, zilganersen, in treating Alexander disease (AxD). The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful stabilization in gait speed. Treatment with zilganersen also showed a favorable safety and tolerability profile. Ionis plans to submit a regulatory filing with the FDA for zilganersen in AxD next year.

Ionis Pharmaceuticals, Inc. (IONS) has announced promising results from a pivotal phase III study of its investigational RNA-targeted therapy, zilganersen, in treating Alexander disease (AxD). The study, which enrolled 54 participants with Alexander disease aged 1.5 to 53 years across 13 sites in eight countries, demonstrated statistically significant and clinically meaningful stabilization in gait speed as assessed by the 10-Meter Walk Test (10MWT) compared to control at week 61 (mean difference 33.3%, p=0.0412). This marks the first time an investigational medicine has shown a positive disease-modifying impact in AxD Ionis Pharmaceuticals, Inc. Announces Positive Topline Results from Pivotal Study of Zilganersen in Alexander Disease^[1].

The study also showed consistent benefit in key secondary endpoints, including changes from baseline in patients' self-identified Most Bothersome Symptom (MBS) Score, Patient Global Impression of Severity (PGIS) Score, and Patient Global Impressed of Change (PGIC) Score at the end of the 60-week double-blind treatment period. Zilganersen demonstrated a favorable safety and tolerability profile, with most adverse events (AE) being mild or moderate in severity and a numerically lower incidence of serious adverse events (SAEs) in the zilganersen arm compared to the control arm Ionis Pharmaceuticals, Inc. Announces Positive Topline Results from Pivotal Study of Zilganersen in Alexander Disease^[1].

Ionis plans to submit a new drug application (NDA) to the U.S. Food and Drug Administration in the first quarter of 2026 and is evaluating the potential to initiate an Expanded Access Program (EAP) in the U.S. Detailed data from the study will be presented at an upcoming medical conference Ionis Pharmaceuticals, Inc. Announces Positive Topline Results from Pivotal Study of Zilganersen in Alexander Disease^[1].

Zilganersen is an investigational antisense oligonucleotide medicine designed to stop the production of excess glial fibrillary acidic protein (GFAP) that accumulates due to disease-causing variants in the GFAP gene. It received Orphan Drug designation and Rare Pediatric designation from both the U.S. FDA and the European Medicines Agency (EMA) Ionis Pharmaceuticals, Inc. Announces Positive Topline Results from Pivotal Study of Zilganersen in Alexander Disease^[1].

Ionis Pharmaceuticals is a leader in antisense technology with a diverse pipeline targeting rare diseases. The company has successfully brought drugs like Spinraza and Tegsedi to market, positioning it uniquely in the market. However, it has faced challenges in revenue growth, with a 3-year revenue growth rate of -6.4% and a net margin of -28.41%. Despite these hurdles, Ionis maintains a robust gross margin of 98.88% and a solid current ratio of 2.87, indicating adequate liquidity to meet short-term obligations Ionis Pharmaceuticals (IONS) Reveals Promising Results for Zilganersen in Alexander Disease Study^[2].

The company's valuation metrics show a mixed picture, with a P/S ratio of 10.81 close to its 5-year high and an Altman Z-Score of 2.2, indicating potential financial stress. However, institutional ownership is high at 106.38%, reflecting strong interest from large investors Ionis Pharmaceuticals (IONS) Reveals Promising Results for Zilganersen in Alexander Disease Study^[2].

Upcoming catalysts, such as the FDA submission for zilganersen, could significantly impact Ionis Pharmaceuticals' stock trajectory. The company's beta of 0.3 suggests lower volatility compared to the broader market, providing some stability for investors.