AstraZeneca and Ionis have suffered a major late-stage setback after Wainua/Wainzua (eplontersen) failed to hit the primary endpoint in a phase 3 trial in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), denting hopes that the RNA-targeted therapy could compete in one of cardiology’s fastest-growing rare disease markets.
Why it matters: The result weakens AstraZeneca’s attempt to expand eplontersen beyond hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), where the drug is already approved in more than 20 countries, including in the EU as Wainzua.
The context: ATTR-CM is a progressive and often underdiagnosed heart disease caused by misfolded transthyretin (TTR) protein building up in the heart. AstraZeneca estimates that 300,000 to 500,000 people live with the condition worldwide.
How it works: eplontersen is a once-monthly RNA-targeted silencer designed to reduce production of transthyretin at its source in the liver.
- That is different from stabilisers such as tafamidis and acoramidis, which aim to prevent the TTR protein from misfolding and forming amyloid deposits. The question for CARDIO-TTRansform was whether silencing TTR could add meaningful benefit on top of today’s standard of care.