Ionis claims first approval for Alexander disease therapy

Ionis' antisense therapy Zanvastro has been approved by the FDA for Alexander disease (AxD), throwing a lifeline to people living with the rare and devastating neurological disorder.

Zanvastro (zilganersen) has been cleared in the US with a broad label that spans both adult and paediatric AxD patients, and becomes the first treatment specifically indicated for the disease, which is thought to affect only a few hundred people in the US, but may be underdiagnosed.

Caused by mutations in the gene that produces GFAP, AxD leads to excess levels of the protein in certain brain cells, damaging neurons and the insulating myelin sheath that surrounds them. It 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.

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 pivotal 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.

"As a mom to a young boy living with Alexander disease and an advocate for this community, I have seen firsthand the profound impact this disease has on individuals and their families," said Emily Petty, president of the End Alexander Disease advocacy group.

Zanvastro's approval is "changing the conversation from 'how do we manage this disease' to 'how can we treat it'," she added. "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."

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 elevated triglycerides. Previously, the company relied on partners to sell its products.

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 paediatric disease priority review voucher (PRV), which can be worth $100 million to $200 million if sold on.