Ionis, AstraZeneca Stumble in ATTR-CM Trial as Rivals Stand to Gain

Ionis Pharmaceuticals Inc. (NASDAQ:IONS) and partner AstraZeneca Plc (NYSE:AZN) said on Thursday that their Phase 3 CARDIO-TTRansform study of eplontersen for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) failed to meet its primary efficacy endpoint.

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In patients receiving contemporary standard of care, including a majority treated with a transthyretin stabilizer, adding eplontersen did not significantly reduce the combined risk of cardiovascular mortality and recurrent cardiovascular clinical events through Week 140 versus placebo.

At baseline, 57% of participants in both treatment groups were receiving stabilizer therapy, while another 24% in each arm started a stabilizer during the study.

Analysts Say Existing ATTR-CM Therapies Benefit From Trial Failure

William Blair wrote on Thursday, “The miss is surprising to us given the well-documented combination use benefit of stabilizers and silencers reported in the HELIOS-B trial of Amvuttra.”

The failure of CARDIO-TTRansform removes a competitor from the ATTR-CM market and is seen as positive for existing therapies, including Alnylam Pharmaceuticals Inc.’s (NASDAQ:ALNY) Amvuttra (vutrisiran) (silencer, same mechanism as eplontersen), BridgeBio Pharma Inc.’s (NASDAQ:BBIO) Attruby (second-gen stabilizer), and Pfizer Inc.’s (NYSE:PFE) tafamidis (first-gen stabilizer).

Trial Results Reinforce Monotherapy Approach

The results also reinforce the view that combining a silencer such as eplontersen with a stabilizer does not improve outcomes, supporting the use of monotherapy and benefiting second-generation treatments like Amvuttra, Attruby and Intellia Therapeutics Inc.’s (NASDAQ:NTLA) nexiguran ziclumeran (nex-z).

Analyst Myles R. Minter said physician discussions had already indicated that second-generation therapies such as Attruby and Amvuttra are differentiated from first-generation tafamidis.

The CARDIO-TTRansform results further suggest that using a single therapy from these newer options is sufficient for treating ATTR-CM patients.

IONS Stock Price Activity: Ionis Pharmaceuticals shares were down 8.96% at $58.51 at the time of publication on Friday, according to Benzinga Pro data.

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