AZ, Ionis build case for amyloidosis drug eplontersen

AstraZeneca and Ionis are waiting for an FDA decision on their new therapy for one of the complications of the disease transthyretin amyloidosis (ATTR) later this year, and now have new data suggesting the drug’s benefits are long-lasting.

Earlier this month, antisense drug eplontersen – licensed from Ionis in a $3.6 billion deal – was filed with the FDA on the strength of 35-week data from the phase 3 NEURO-TTRansform trial in patients with polyneuropathy associated with hereditary ATTR.

Now, the two companies say longer-term follow-up shows the drug efficacy is maintained for 66 weeks, with the drug hitting co-primary endpoints on neuropathic disease progression, quality of life scores and reduction of the levels of disease biomarker TTR in the blood compared to an external placebo group.

Patients with hereditary ATTR with polyneuropathy suffer debilitating nerve damage throughout their body resulting in the progressive loss of motor function that typically leads to disability within five years of diagnosis and can be fatal within 10.

AZ paid $200 million upfront in 2021 to partner eplontersen, Ionis’ second drug for ATTR after Tegsedi (inotersen), which has lagged in the ATTR polyneuropathy market behind Alnylam’s Onpattro (patisiran), as well as Pfizer’s Vyndaqel/Vyndamax (tafamidis), which is also approved to treat cardiomyopathy associated with the disease.

AZ and Ionis hope eplontersen can mount a stronger challenge in the market, aided by a subsequent filing in cardiomyopathy – assuming the results of the ongoing phase 3 CARDIO-TTRansform are positive when it reads out in the first quarter of 2025.

Tegsedi and Onpattro are also in cardiomyopathy trials, potentially setting up an intriguing four-way marketing tussle for market share in that category, as well as polyneuropathy.

“With limited treatment options currently available, there is an urgent unmet medical need for new therapies and earlier, accurate diagnosis across the different types of this systemic, progressive, and fatal condition,” commented AZ’s head of R&D, Mene Pangalos.

Analysts at GlobalData predicted recently that orally-active Vyndaqel may eventually lose out to its rivals, as they seem to offer great efficacy, despite being given via a needle. Pfizer booked almost $2.5 billion from the drug last year.

As they wait for the outcome of the FDA’s deliberations by 22nd December, AZ and Ionis maintain that eplontersen has “best-in-class” credentials that will be apparent when the full results from NEURO-TTRansform – both 35-week and 66-week data – are presented at the American Academy of Neurology (AAN) annual meeting in April.

Among the characteristics that separate eplontersen is that it is suitable for self-administration by patients once a month, whereas Onpattro – currently its closest rival – has to be administered intravenously in a clinic every three weeks. Tegsedi can also be self-injected, but once every seven days.