AstraZeneca and Ionis Pharmaceuticals announced on July 9 that their antisense therapeutic Wainua did not demonstrate significant cardiovascular benefit in a Phase 3 study of patients with transthyretin-mediated amyloid cardiomyopathy. The companies said Wainua, when added to standard of care, "did not meet the primary efficacy endpoint," which was a composite of cardiovascular mortality and recurrent cardiovascular clinical events compared to placebo after up to 140 weeks of follow-up.
Stifel analysts called the outcome "surprising" in a note to investors, saying, "The study here was expected to work since we know TTR [transthyretin] silencers are effective." H.C. Wainwright had previously assigned a "75% probability of approval" for Wainua in this indication. Stifel also said that Wainua's potential approval was "a key valuation driver" for Ionis and described the results as "obviously a negative" for the company. Following the announcement, Ionis shares dropped by 20% in premarket U.S. trading while AstraZeneca shares fell by 9% on the British stock exchange.
The companies plan to conduct a full analysis of the results and present their findings at an upcoming medical congress next month. There was no mention from AstraZeneca or Ionis regarding future regulatory plans for Wainua in ATTR-CM. Stifel said that, “trying to approach regulators here on these data would seem like a stretch.”
Wainua received its first approval in December 2023 for treating polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (hATTR-PN). The drug originated at Ionis before AstraZeneca obtained joint development and commercialization rights through an agreement reached in December 2021, which included $200 million upfront, additional payments upon regulatory approvals totaling $485 million, up to $2.9 billion tied to sales milestones, plus royalties.
The CARDIO-TTRansform trial enrolled more than 1,400 patients already receiving standard care who were randomly assigned either add-on Wainua or placebo treatment. The result comes as BridgeBio recently reported posthoc data indicating its transthyretin stabilizer Attruby preserved kidney function in patients with ATTR-CM—a benefit Jefferies analysts described as “distinct” from other drugs available for this condition.
Stifel wrote that the failure is “absolutely the most complicated possible outcome” for Alnylam Pharmaceuticals, another competitor marketing Amvuttra for ATTR-CM but also developing nucresiran currently undergoing Phase 3 trials.
