The ATTR-CM drug race almost got another contender, but AstraZeneca and Ionis’ Wainua unexpected Phase 3 trial failure might have actually simplified the field.
- Wainua earned FDA approval in 2023 for ATTR-polyneuropathy, bringing in $212M in 2025, with Ionis collecting $49M in royalties.
- It belongs to the TTR silencer drug class, which is already known to be effective in ATTR-CM, so the trial was widely expected to succeed.
Initially intended to support FDA approval, the Phase 3 CARDIO-TTRansform study enrolled 1,432 patients and randomized them to Wainua or placebo plus standard of care, with results showing that…
- The trial missed its primary endpoint of reducing cardiovascular deaths or repeat CV events over a 140 week follow-up.
- Most patients were also receiving a stabilizer drug (57% at baseline in each arm, with another 24% adding one during the trial).
- One patient subgroup was assigned to Wainua as a monotherapy and saw a 29% risk reduction, so it’s worth noting the therapy still worked to an extent.
The most likely culprit for these results is how ATTR-CM treatment is evolving rather than an ineffective drug.
- According to Ionis, the data speaks to how effective ATTR stabilizers have become, making the add-on benefits of Wainua hard to demonstrate.
- That said, Alnylam’s HELIOS-B trial, which tested the silencer-plus-stabilizer combo did show benefit, so there is a question as to why Wainua couldn’t replicate that.
Two other players stand to gain. BridgeBio’s stabilizer Attruby, which binds TTR rather than silencing it, looks emboldened, as does Intellia’s one-time CRISPR gene therapy nex-z, developed with Regeneron.
- With Wainua out of the running, Attruby’s sales are also likely to climb (it brought in $362.4M in 2025).
But these Phase 3 results also cut against Alnylam’s next-generation bet. The company is already developing nucresiran (a silencer like Wainua) with the TRITON-CM trial expected to read out in 2030.
- The Wainua miss now raises questions about whether a next-gen silencer can prove itself in a stabilizer-dominated market.
And of course, it wouldn’t be cardio-pharma news without a mention of AZ and Ionis’ stock.
- Ionis shares fell around 20% and AstraZeneca dropped 7%, while rivals Alnylam and BridgeBio rose roughly 10% and 15% respectively.
- The failure leaves Alnylam’s Amvuttra as the only approved TTR silencer for ATTR-CM.
The Takeaway
While the CARDIO-TTRansform trial isn’t a win for Astrazeneca/Ionis’ Waiuna, it helps clarify where the real effective therapy for ATTR-CM stems from. For now, this trial’s results point to TTR stabilizers rather than silencers as the way to go
