Eplontersen for Transthyretin Amyloid Cardiomyopathy

The negative result suggests combining a silencer with a stabilizer adds less benefit than assumed

Drop-in of stabilizers during the trial limited estimation of eplontersen's true monotherapy effect

57% already on a stabilizer at baseline and more started during follow-up, diluting any added benefit

The topline was very surprising but the full dataset holds much to unpack

Eplontersen did not lower the composite risk versus placebo through 140 weeks

The key question was whether eplontersen could dethrone tafamidis in ATTR-CM

Noted the overall miss on the primary endpoint and flagged the exploratory signal favoring eplontersen in patients without background stabilizer therapy.

Summarized eplontersen's sustained TTR suppression alongside the negative primary outcome at 140 weeks.

Highlighted the disconnect between circulating TTR reduction and the failure to move the primary endpoint.

Noted the trial did not meet its primary endpoint in a population where roughly 60% were already on stabilizer therapy, and flagged the exploratory question of efficacy without background stabilizer.

Reported eplontersen did not significantly reduce the primary composite versus placebo at 140 weeks.

Summarized the neutral primary result while noting preserved functional capacity and quality of life with eplontersen.

Noted huge interest and packed discussion sessions at ESC around the ATTR-CM space and CARDIO-TTRansform.

“Even if you never care for patients with cardiac amyloidosis, the CARDIO-TTRansform trial offers lessons in looking beyond soundbite of a clinical trial to understand what the findings really mean for patient care.”

“We believe these findings reflect the rapidly evolving treatment landscape, in which contemporary ATTR-CM patients are widely treated with stabilizers. Although we are disappointed that the study did not meet the primary endpoint, these results have the potential to guide the treatment landscape for ATTR-CM and contribute to advancing future care for patients.”

“Results from cardioTTRansform. Eplontersen (ASO) did not improve survival in Amyloidosis (85%WT, 15%) already on tafamidis. #ESC Main Arena, Múnich”

“Mat Maurer presentating the results of the CARDIO-TTRansform trial. We are so thankful to our/all patients who enrolled in this trial. Lots of learnings here. Lots more to do. Simultaneously published in”

“The CARDIO-TTRansform trial was designed to examine the role of Wainua, a gene silencer treatment, on top of today's standard of care in reducing recurring cardiovascular events and mortality. Although the trial did not meet its primary objective, we believe the results support greater scientific understanding of treatment approaches for the hundreds of thousands of patients worldwide suffering from this progressive and often fatal condition.”