EU clears AZ, Ionis' Wainzua for ATTR polyneuropathy

AstraZeneca and Ionis Pharma have an EU green light for their Wainzua therapy for hereditary transthyretin-mediated amyloidosis (ATTR) polyneuropathy, building on earlier approvals in the US and UK for the would-be blockbuster.

The European Commission has cleared Wainzua (eplontersen) – known as Wainua in the US – to treat adults with ATTR and stage 1 or stage 2 (mild to moderate) polyneuropathy. It is the first treatment option for the disease that can be self-administered once a month by patients using a pen-injector, rather than being administered by a healthcare professional.

That differentiates the product from Alnylam's Amvuttra (vutrisiran), which was approved in the EU in 2022 for the same indication and comes formulated in prefilled syringes with a dose needed every three months.

Both drugs work by inhibiting the production of the TTR protein that accumulates in ATTR, causing tissue damage. When it affects the nerves, leading to ATTR-PN, symptoms include pain, discomfort, progressive weakness and loss of sensation in the legs and arms, and mobility difficulties.

The EU approval comes on the back of the NEURO-TTRansform trial, which showed that Wainzua reduced levels of TTR by 82%, while a placebo group saw an 11% reduction and also reduced the progression of neurological impairment.

The drug is also being developed to treat cardiomyopathy associated with ATTR and is in a 1,400-patient phase 3 trial (CARDIO-TTRansform), due to read out in the first half of this year. That could be a more substantial opportunity, with 300,000 to 500,000 patients estimated worldwide, compared with up to 40,000 for ATTR polyneuropathy.

In Ionis' fourth-quarter results call, the company's global product strategy chief, Kyle Jenne, said it "couldn't be more pleased" with the initial rollout of Wainua, with "accelerating sequential growth" that drove full-year 2024 sales to $85 million, with $42 million of that coming in the fourth quarter, earning Ionis $20 million in royalties.

It is expecting sales to ramp up further this year, although the drug still has a long way to go to catch Amvuttra, which made $970 million in 2024, as well as Pfizer's daily oral therapy Vyndamax/Vyndaqel (tafamidis), which is approved for both ATTR polyneuropathy and cardiomyopathy and made almost $5.5 billion worldwide last year but is in the last few years of its patent life.

AZ licensed Wainzua from Ionis in a $3.6 billion deal in 2021 and sees the drug as a future pillar of its cardiovascular, renal, and metabolism (CVRM) business unit. Some analysts agree that it has strong sales potential – possibly able to bring in $1 billion or more at peak – assuming it also gets approval for the ATTR cardiomyopathy indication.