AstraZeneca’s $200 million bet on Ionis Pharmaceuticals’ rare disease drug has delivered an early win. A phase 3 trial of eplontersen in hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN) hit the mark at an interim analysis, teeing the British Big Pharma up to make an approval filing that will keep it hot on the heels of Alnylam.
Ionis granted AstraZeneca rights to its ligand-conjugated antisense candidate in the final days of last year, pocketing $200 million upfront and positioning itself to receive up to $3.4 billion in milestones, most of which are tied to sales thresholds. In return, AstraZeneca secured the right to jointly commercialize the drug in the U.S., plus exclusive rights in the rest of the world, and thereby established itself as a player in the competitive ATTR space.
ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability and is usually fatal. To evaluate the effect of eplontersen in ATTRv-PN, the smaller of the two opportunities open to eplontersen, Ionis enrolled 168 participants and compared their outcomes to the external placebo group from its Tegsedi registrational clinical trial. Participants received eplontersen by subcutaneous injection every four weeks.
At the planned 35-week interim analysis, the researchers saw statistically significant changes in the concentration of serum transthyretin, indicating a reduction in the TTR protein that drives ATTR, and on a measure of neuropathic disease progression. The changes caused the clinical trial to hit its co-primary endpoints.
AstraZeneca reported that the trial met a secondary endpoint that looked at patient-reported quality of life. With the trial also delivering “a favorable safety and tolerability profile with no specific concerns,” according to AstraZeneca, the partners think they have the data to support a filing for FDA approval of the candidate this year.
If approved, eplontersen will go up against Alnylam’s Amvuttra. The drug, which was known as vutrisiran during its development, won FDA approval in ATTR polyneuropathy in adults last week, after a two-month delay. Amvuttra is an RNAi therapeutic, administered every three months, that halted or reversed disease in more than half of the patients in a phase 3 trial. AstraZeneca and Ionis will share the phase 3 data that will dictate whether eplontersen is competitive at an upcoming medical meeting.
The competition in amyloid transthyretin cardiomyopathy, a form of ATTR that affects the heart that analysts at Jefferies estimate is a 10 times larger opportunity than ATTRv-PN, is fiercer still. Pfizer is already racking up blockbuster sales with Vyndaqel and Vyndamax, Alnylam is working to deliver phase 3 data on Onpattro and vutrisiran, and BridgeBio Pharma still hoping to establish acoramidis as a player despite failing a late-stage study last year. Success in cardiomyopathy will determine how much Ionis gets of the $3.4 billion in milestones.