zilganersen (ION373) / Ionis - LARVOL DELTA

Zilganersen Expanded Access Program for Individuals With Alexander Disease (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Ionis Pharmaceuticals, Inc.

New trial • CNS Disorders • Rare Diseases • FAP • GFAP

Ionis announces zilganersen New Drug Application for Alexander disease (AxD) accepted by FDA for Priority Review (Businesswire) - "The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of September 22, 2026....The NDA and Priority Review designation were based on results from the pivotal study of zilganersen in children and adults living with AxD."

FDA filing • PDUFA • Priority review • Genetic Disorders

Alexander Disease: A Literature Review for Clinicians. (PubMed, J Child Neurol) - "Current management is supportive, but emerging gene-targeted approaches, including antisense oligonucleotides such as zilganersen and AAV-mediated gene silencing strategies, offer promising therapeutic prospects. This review provides an updated overview of the clinical, radiologic, genetic, and molecular features of ALEXD, emphasizing its spectrum of phenotypes across age groups and ongoing efforts toward improved diagnosis and targeted treatment."

Journal • Review • Ataxia • CNS Disorders • Developmental Disorders • Epilepsy • Movement Disorders • Rare Diseases • FAP • GFAP

Efficacy and Safety of Zilganersen, an Investigational RNA-targeted Antisense Therapy, in People Living with Alexander Disease: Results from a Pivotal Study (AAN 2026) - P3 | "Zilganersen shows potential as a disease-modifying therapy for AxD, with statistically significant and clinically meaningful stabilization of motor function, a consistent trend towards benefit across key secondary endpoints, a favorable safety profile, and target engagement vs control."

Clinical • CNS Disorders • Rare Diseases • FAP • GFAP

Recent Highlights - Wholly Owned Medicines: Zilganersen (Businesswire) - "Zilganersen on track for launch this year as the first and only medicine to demonstrate clinically meaningful and disease-modifying impact in children and adults with Alexander disease (AxD), assuming approval: NDA submitted with approval decision anticipated in H2:2026; Expanded access program (EAP) in U.S. underway."

FDA approval • FDA filing • Genetic Disorders

Ionis receives U.S. FDA Breakthrough Therapy designation for zilganersen for Alexander disease (AxD) (Ionis Pharmaceuticals Press Release) - "Ionis plans to submit an NDA to the U.S. FDA in Q1 2026 and is working to initiate an Expanded Access Program (EAP) in the U.S."

Breakthrough therapy • FDA filing • Genetic Disorders

Recent Highlights - Wholly Owned Medicines: Zilganersen (Businesswire) - "NDA submission planned for the first quarter of 2026 with approval anticipated next year."

FDA approval • FDA filing • Genetic Disorders

A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD) (clinicaltrials.gov) - P3 | N=54 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Rare Diseases • FAP • GFAP

Case Study: EEG-Guided Sedation in a Pediatric Patient with Alexander's Disease (IARS-SOCCA 2025) - "The patient was enrolled in a clinical trial studying the efficacy of intrathecal ION373, an antisense oligonucleotide-based therapy administered via intrathecal infusion under general anesthesia that inhibits the amount of GFAP protein produced...In past procedures, the patient was induced with sevoflurane and maintained on a regimen of propofol ranging from 100 mcg/kg/min to 200 mcg/kg/min...In this report we show how EEG was used to guide anesthetic care for a pediatric patient with Alexander's Disease, reducing the amount of propofol used by 50% and leading to notably shorter wash-off time and time to emergence from anesthesia.We believe that this patient's increased sensitivity to propofol measured through the EEG could be explained by the effects of Alexander's Disease on astrocyte metabolism. Astrocytes play a key role in the regulation of neuronal metabolism.5 Past work has shown that anesthetic drugs impair neuronal mitochondrial function, shifting..."

Case study • Clinical • Anesthesia • CNS Disorders • Developmental Disorders • Epilepsy • Hypotension • Pediatrics • Solid Tumor • GFAP

Zilganersen granted U.S. FDA Fast Track designation for people living with Alexander disease (PRNewswire) - "Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that the U.S. Food and Drug Administration (FDA) has granted zilganersen Fast Track designation for the treatment of children and adults with an ultra-rare, progressive and ultimately fatal neurological disorder known as Alexander disease (AxD). Topline data from the pivotal study of zilganersen is expected in the second half of 2025. The FDA grants investigational medicines Fast Track designation to facilitate the development and expedite the review of medicines that demonstrate the potential to treat serious conditions and fill an unmet medical need."

Fast track • P3 data: top line • Genetic Disorders

A Study to Evaluate the Safety and Efficacy of Zilganersen (ION373) in Patients With Alexander Disease (AxD) (clinicaltrials.gov) - P3 | N=73 | Enrolling by invitation | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Enrolling by invitation | Trial completion date: Mar 2029 ➔ Sep 2029 | Trial primary completion date: Mar 2025 ➔ Sep 2025

Enrollment status • Trial completion date • Trial primary completion date • CNS Disorders • Rare Diseases • FAP • GFAP

A Study to Evaluate the Safety and Efficacy of ION373 in Patients With Alexander Disease (AxD) (clinicaltrials.gov) - P3 | N=73 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Trial completion date: Nov 2025 ➔ Mar 2029 | Trial primary completion date: Feb 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • CNS Disorders • Rare Diseases • GFAP

"We also entered our late-stage pipeline with the initiation of pivotal studies for ION363 in patients with FUS-#ALS. And the ION373 in patients with #Alexandersdisease. #raredisease #neurotwitter #MedTwitter #neurolgy #ALSAwarenessMonth $ions $biib" (@IonisDisrupts)

Clinical • Amyotrophic Lateral Sclerosis • Rare Diseases

A Study to Evaluate the Safety and Efficacy of ION373 in Patients With Alexander Disease (AxD) (clinicaltrials.gov) - P3; N=58; Recruiting; Sponsor: Ionis Pharmaceuticals, Inc.; Not yet recruiting ➔ Recruiting

Enrollment open • GFAP