Community Statement 

September 22, 2025 

Dear Alexander disease community, 

Ionis announced today positive initial results from the pivotal clinical trial (NCT: 04849741)¹ of zilganersen (ION373) in people with Alexander disease (AxD). In the announcement, Ionis reported that zilganersen (50 mg) demonstrated statistically significant and clinically meaningful stabilization on the primary endpoint of gait speed as assessed by the 10-Meter Walk Test at week 61 (mean difference 33.3%, p=0.0412), with favorable safety and tolerability, as compared to control. Zilganersen also demonstrated consistent benefit in key secondary endpoints. These data mark the first time an investigational medicine has shown a potential disease-modifying impact in Alexander disease.² 

Ionis expresses sincere gratitude to the 54 patients and their caregivers and families who bravely volunteered to participate in this clinical trial and the countless staff at study sites who supported them over the last four years.² We also wish to acknowledge the substantial contributions of Ionis’ academic collaborators, whose support and partnership helped make this achievement possible.

Ionis also announced today that it will engage with regulators at the U.S. Food and Drug Administration (FDA) and submit a New Drug Application (NDA) in the first quarter of 2026.² As a reminder, neither the FDA nor any other regulatory agency has reviewed the safety and efficacy data of zilganersen (ION373). 

Finally, Ionis thanks the entire AxD and broader leukodystrophy community for its support, partnership, patience, and perseverance. We are at this moment because of our years-long partnership, and we look forward to sharing additional updates. 

Sincerely, 

The Ionis Zilganersen Team 

Please see the following information which you may find helpful: 

Where can someone get more information about the zilganersen clinical trial results? 

We recognize that people will have questions about today’s announcement of initial results from the pivotal study and encourage those seeking more information to speak with their doctor or study site, if they’re currently enrolled in the study. 

How do the study results impact individuals who are enrolled in the current trial? 

Individuals enrolled in the study can continue to receive zilganersen as part of the open-label long-term extension part of the trial. Trial participants seeking additional information should speak to their study site. 

Will Ionis pursue marketing authorization for zilganersen as a treatment for Alexander disease? 

Ionis announced today that it will work with urgency to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in early 2026.² If the NDA is accepted by the FDA, Ionis will work together with the agency to support, as appropriate, a thorough and efficient review of the application. To learn more about how the FDA regulates and approves drugs, visit their website.³ Ionis has not yet disclosed plans to pursue marketing authorization in regions outside of the U.S. 

Will Ionis offer an Expanded Access Program (EAP) to zilganersen while the application is under review? 

Ionis is evaluating the potential to initiate an Expanded Access Program (EAP) in the U.S. However, no EAP has been activated at this time. Ionis will provide updates to all stakeholders, including the AxD community, when appropriate. Should the company initiate an EAP, additional information will be made available here.⁴ A person’s doctor should be their primary source of information on this topic. 

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The End Alexander Disease Foundation, Elise’s Corner, Alex TLC, and United Leukodystrophy Foundation are additional community resources that provide education and support to those affected by Alexander disease. 

For more information about Ionis, please visit www.ionis.com or contact us at padvocacy@ionis.com. 

Abbreviations: AxD, Alexander disease; FDA, U.S. Food and Drug Administration; NDA, new drug application. 

References: 1. A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD). Updated August 26, 2025. Accessed September 21, 2025. https://clinicaltrials.gov/study/NCT04849741, 2. Ionis announces positive topline results from pivotal study of zilganersen in Alexander disease. Published September 22, 2025., 3. Overview of our role regulating and approving drugs | Video series. Updated November 21, 2024. Accessed September 21, 2025. https://www.fda.gov/drugs/information-consumers-and-patients-drugs/overview-our-role-regulating-and-approving-drugs-video-series., 4. Ionis Expanded Access Policy. Updated December 2024. Accessed September 21, 2025. https://ionis.com/patients-and-advocacy/expanded-access-policy.