FDA approves Ionis, AZ’s Wainua for ATTR polyneuropathy

AstraZeneca and Ionis are planning a US launch next month for Wainua, their treatment for polyneuropathy in life-threatening disease transthyretin-mediated amyloidosis (ATTR), after getting FDA approval for the would-be blockbuster.

The US approval is the first in the world for Wainua (eplontersen), a once-monthly antisense treatment that can be self-administered by subcutaneous injection. According to AZ and Ionis, it is the only drug for ATTR polyneuropathy that doesn’t need to be administered by a healthcare professional.

ATTR is a debilitating disease affecting up to half a million people worldwide that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade. Wainua works by reducing levels in the body of TTR protein, which builds up as fibrils in tissues and damages them.

In the NEURO-TTRansform trial Wainua reduced levels of TTR by 82%, while a placebo group saw an 11% reduction, and reduced disease progression.

The approval fires a warning shot across the bows of Alnylam and Pfizer, which both have big-selling drugs on the market for ATTR polyneuropathy that could be threatened by Wainua.

Alnylam’s Onpattro (patisiran) – given by intravenous infusion every three weeks – has been approved for ATTR polyneuropathy since 2018. It was joined last year by follow-up Amvuttra (vutrisiran), which requires a doctor-administered subcutaneous injection every three months and has quickly overtaken its predecessor in the market. The two drugs made $81 million and $149 million, respectively, in the third quarter of this year.

Pfizer meanwhile sells daily oral therapy Vyndamax/Vyndaqel (tafamidis), which made $892 million in third-quarter sales across its approvals in ATTR polyneuropathy as well as cardiomyopathy, another consequence of the disease.

The question for AZ and Ionis is whether self-administration will be a draw for patients and their doctors as they try to drive uptake of Wainua, which has also been filed with regulators in Europe and elsewhere.

AZ sees the drug as a future pillar of its cardiovascular, renal and metabolism (CVRM) business unit, and some analysts agree that it has strong sales potential with the potential to bring in $1 billion or more at peak – assuming it also gets approval for ATTR cardiomyopathy.

Meanwhile, there is a large, as-yet untreated patient population that could allow plenty of room in the market for all the drugs if it can be addressed. There’s also no word yet on the price of Wainua, which will also have a bearing on its take-up.

Importantly for Ionis, Wainua will be its first commercial launch, having previously relied on partners to sell its drugs. It will co-market the drug with AZ in the US, while the latter has exclusive rights in ex-US markets.

After launch, the next major development for Wainua will be the results of the 1,400-patient CARDIO-TTRansform study in ATTR cardiomyopathy, which completed enrolment in the summer and is due to generate preliminary results next year.

AZ licensed rights to eplontersen in 2021 for $200 million upfront in a deal valued at up to $3.6 billion.