The neurological deterioration and progressive muscle weakness caused by Alexander disease has its first FDA-approved therapy, a genetic medicine that Ionis Pharmaceuticals designed to address the underlying driver of this life-threatening orphan disorder.
The late Thursday regulatory decision for the Ionis drug, zilganersen, covers the treatment of both children and adults with Alexander disease. Now set to be commercialized under the brand name Zanvastro, this new product is a key piece of the Carlsbad, California-based biotech’s unfolding new business strategy.
Alexander disease stems from mutations in the gene that provides instructions for making glial fibrillary acidic protein (GFAP). Normal versions of this protein provide support for astrocytes, a type of cell found throughout the central nervous system. Mutated GFAP accumulates in these cells, leading to nervous system damage that manifests as seizures, developmental problems, muscle weakness, and increased pressure in the brain. The disease is ultra-rare, estimated to occur just once in every one million to three million people worldwide.
Zanvastro is an antisense oligonucleotide designed to bind to and degrade pre-messenger RNA for GFAP, reducing synthesis of the disease-driving protein. Similar to many neuroscience medicines, Zanvastro is administered as an intrathecal injection. The dosing interval is every three months.
Approval of Zanvastro comes nearly a year after Ionis reported results from a placebo-controlled pivotal clinical trial whose main goal was assessing the 49 trial participants in a 10-meter walk test. At week 61, results showed patients treated with the study drug achieved statistically significant and clinically meaningful stabilization of gait speed compared to the control group, which showed deteriorating gait speed. In addition to improved motor function, blood tests showed evidence that the drug engaged its target and modulated the underlying cause of the disease. Adverse reactions were classified as mild or moderate; the most common ones included vomiting, back pain, and cough.
Ionis estimates that 300 patients in the U.S. have Alexander disease, Chief Global Product Strategy Officer Kyle Jenne said during a Friday morning conference call. The company is working to get Zanvastro into distribution channels and the product will become available shortly carrying a list price of $285,000 per dose, he said. With dosing every three months, that works out to $1.14 million a year before any insurance rebates or discounts.
Ionis has experience with neuroscience drugs through the spinal muscular atrophy medicine Spinraza and Qalsody, which is approved for a rare form of amyotrophic lateral sclerosis. Both products are marketed by Biogen under a partnership.
Ionis has been shifting away from partnering out its internally developed assets, choosing to instead handle commercialization. Tryngolza, approved for familial chylomicronemia in 2024 and in June for severe hypertriglyceridemia, was Ionis’s first product in this strategy. Next was Dawnzera, approved last summer for preventing attacks from the rare swelling disorder hereditary angioedema. With the approval of Zanvastro, the first neurology medicine that Ionis will commercialize on its own, the most advanced candidate in the pipeline is now obudanersen, an antisense oligonucleotide in Phase 3 development for Angelman syndrome. Ionis expects data from this study in the second half of 2027.
While Ionis’s new business strategy emphasizes retaining U.S. commercialization rights for its drugs, the company is still open to partnerships in the rest of the world. In June, Recordati licensed ex-U.S. rights to the Alexander disease drug for $30 million up front plus royalties on sales of an approved product. Recordati assumes responsibility for regulatory submissions in other markets.
FDA approval of Zanvastro came with a priority review voucher, a regulatory fast pass that a recipient may use to accelerate the review of a future rare pediatric disease drug candidate. Many biotechs opt to sell vouchers to big pharma companies as a way to raise non-dilutive capital. Ionis can decide what to do with the voucher from a position of financial strength. As of the end of the June, the company reported its cash position was about $2.1 billion. During the conference call, Ionis CEO Brett Monia said Ionis is still weighing its options, but he acknowledged the voucher could be applied to an asset in the pipeline, which currently spans eight medicines in clinical development.
“That’s priority now and that pipeline is going to grow,” Monia said. “We’re expecting additional neurology medicines to enter the clinic in the near future.”
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