AZ, Ionis get CHMP backing for ATTR polyneuropathy drug

AstraZeneca and Ionis are set fair for EU approval of Wainzua, their treatment for polyneuropathy associated with transthyretin-mediated amyloidosis (ATTR), after the EMA's human medicines committee backed the drug.

The CHMP issued a positive opinion on the once-monthly RNA-targeting treatment at its October meeting, putting it on course to become the first drug for ATTR polyneuropathy in the EU that can be self-administered by patients, rather than a healthcare professional.

Wainzua (eplontersen) – which is already approved as Wainua in other markets, including the US and Canada – works by preventing the production of the TTR protein that becomes accumulated in ATTR, causing damage to tissues such as the heart and the peripheral nerves. It affects around half a million people around the world, causing disability, and can be fatal if untreated.

The CHMP's decision was based on the results 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), which is due to read out within the next few months.

AZ sees Wainzua 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 the ATTR cardiomyopathy indication.

For Ionis, Wainzua is 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.

The drug – which, according to AZ, has shown "encouraging launch uptake" in its first few months on the market – is competing with drugs from Alnylam and Pfizer, with the big question now whether self-administration will differentiate it from its rivals.

Alnylam has two drugs for ATTR polyneuropathy – Onpattro (patisiran), which is given by intravenous infusion every three weeks, and newer Amvuttra (vutrisiran), which requires a doctor-administered subcutaneous injection every three months – which made $355 million and $558 million in sales, respectively, last year.

Amvuttra has also cleared a phase 3 trial in cardiomyopathy, which analysts at Goldman Sachs have suggested could be the key to driving sales to $5 billion a year.

Pfizer, meanwhile, sells daily oral therapy Vyndamax/Vyndaqel (tafamidis), which is approved for both ATTR polyneuropathy and cardiomyopathy and made more than $3.3 billion worldwide last year. It is approaching the end of its market exclusivity, however, as basic product patents are due to expire at the end of this year in the US and in 2026 in Europe.

Pfizer has been working to extend its patent life, but several generic drugmakers have filed copycat versions for approval, prompting patent infringement lawsuits.

Another potential is BridgeBio and Bayer's acoramidis, which has also shown efficacy in a phase 3 ATTR cardiomyopathy trial and is heading for a possible FDA approval in November.

Image by Brian Penny from Pixabay