The FDA has approved Ionis’ antisense therapy Zanvastro for Alexander disease (AxD), a rare and devastating neurological disorder. This approval provides a treatment option for people living with AxD, which is thought to affect only a few hundred people in the US, but may be underdiagnosed.
Zanvastro (zilganersen) has been cleared in the US with a broad label that spans both adult and pediatric AxD patients, becoming the first treatment specifically indicated for the disease.
Alexander Disease and Its Causes
AxD is caused by mutations in the gene that produces GFAP, leading to excess levels of the protein in certain brain cells, damaging neurons and the insulating myelin sheath that surrounds them. This results in serious and life-threatening symptoms like seizures, delayed development, difficulty walking, and muscle weakness.
A recent study drawing on data from the UK Biobank suggested that the GFAP gene mutation is almost 200 times more common than previously thought.
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Treatment and Clinical Trials
Until now, treatment of AxD has primarily been limited to managing symptoms, but patients, their families, and clinicians now have an option that can address the underlying disease mechanism. Zanvastro, administered every three months into the cerebrospinal fluid (CSF), has been shown to reduce the production of GFAP.
In a trial in 49 patients, Zanvastro was shown to improve clinical measures, including walking speed and other motor skills over 60 weeks of follow-up, while those in an untreated control group declined.
Emily Petty, president of the End Alexander Disease advocacy group, has seen firsthand the profound impact this disease has on individuals and their families. She stated that Zanvastro’s approval is changing the conversation from managing the disease to treating it.
For far too long, receiving a diagnosis of Alexander disease was accompanied by uncertainty and the difficult reality that there were no available treatments. Today, that begins to change, according to Emily Petty.
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Commercial Presence and Future Plans
Zilganersen is one of the four products Ionis plans to self-market in the US to build its commercial presence, and it is the second to be approved by the FDA after Tryngolza (olezarsen) for lipid disorders associated with raised triglycerides.
In June, Ionis licensed zilganersen in all countries outside the US to Italy’s Recordati, which has said it plans to file the drug for approval in Europe next year.
Pricing plans in the US have not been revealed yet, but analysts at William Blair have predicted that Zanvastro could reach $295 million in peak global sales. The approval also earns Ionis a pediatric disease priority review voucher (PRV), which can be worth $100 million to $200 million if sold on.
Zanvastro provides a new option for patients and clinicians, and its approval marks an important step forward in the treatment of this rare and devastating disease.
