Ionis licenses global rights outside the U.S. for investigational Alexander disease therapy zilganersen to Recordati as the FDA reviews the first potential disease-modifying treatment ahead of its September 22 PDUFA date.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Ionis Pharmaceuticals has entered a global licensing agreement with Recordati to commercialize zilganersen, an investigational antisense oligonucleotide therapy for Alexander disease (AxD), in all markets outside the United States. Ionis will retain exclusive commercialization rights in the U.S. while continuing to lead global clinical development.
Under the agreement, Recordati will oversee regulatory submissions, market access activities, and commercialization across international markets, including country-specific early access programs where applicable. Ionis will receive an upfront payment of $30 million and remains eligible for milestone payments and tiered royalties reaching the mid-20% range of annual net sales.
The partnership comes as zilganersen undergoes U.S. Food and Drug Administration (FDA) review, with a Prescription Drug User Fee Act (PDUFA) target action date of September 22, 2026. If approved, the therapy would become the first disease-modifying treatment for Alexander disease and mark Ionis’ first independent commercial launch in neurology.
Zilganersen Targets the Genetic Cause of Alexander Disease
Zilganersen is an investigational antisense oligonucleotide (ASO) that reduces production of glial fibrillary acidic protein (GFAP), which accumulates because of disease-causing variants in the GFAP gene. Excess GFAP damages astrocytes, leading to progressive neurological decline.
Alexander disease is an ultra-rare, progressive, and frequently fatal neurodegenerative disorder affecting approximately one to three people per million worldwide. Patients gradually lose mobility, independence, swallowing function, and airway protection. Survival is typically 14 to 25 years after symptom onset, and no disease-modifying therapies are currently approved.
The FDA has granted zilganersen Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations, while the European Medicines Agency (EMA) has awarded Orphan Drug designation.
Pivotal Study Demonstrated Clinically Meaningful Benefit
Recent data from the pivotal study reinforced previously reported positive topline results. The trial met its primary endpoint in participants aged 5 years and older, with the 50 mg dose producing statistically significant and clinically meaningful stabilization of gait speed compared with control at Week 61, measured using the 10-Meter Walk Test (10MWT).
Secondary and exploratory assessments, including clinician- and caregiver-reported outcomes, consistently favored zilganersen across multiple symptoms of Alexander disease, supporting broad functional benefit.
The therapy also demonstrated a favorable safety profile. Most adverse events were mild to moderate, while serious treatment-emergent adverse events (TEAEs) occurred less frequently in patients receiving zilganersen than in the pooled control group (37.5% vs. 47.1%).
Partnership Expands Global Access Strategy
Ionis Chief Executive Officer Brett P. Monia, Ph.D. said Recordati’s established rare disease infrastructure and expertise in regional regulatory pathways make the company well positioned to accelerate access for patients outside the United States.
Recordati Chief Executive Officer Rob Koremans said the agreement strengthens the company’s rare disease portfolio and combines Ionis’ innovation with Recordati’s global commercialization capabilities to maximize access to a therapy that could address a major unmet medical need.
Regulatory Path Forward
The collaboration positions Recordati to lead international commercialization while Ionis prepares for a potential U.S. launch following the FDA decision expected in September. If approved, zilganersen could establish a new treatment standard for Alexander disease and represent a major milestone for both companies in rare neurological disorders.
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About the Writer
Chikkula Pavan Kumar (LinkedIn), PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.