ACO-SWITCH to Evaluate Tafamidis-to-Acoramidis Switch in ATTR-CM

A newly published protocol describes ACO-SWITCH (NCT07298044), a prospective, open-label, multicenter, single-arm phase 4 study evaluating changes in serum transthyretin (sTTR) levels after patients with transthyretfin amyloid cardiomyopathy (ATTR-CM) switch from tafamidis to acoramidis.¹ The trial will enroll 50 adults aged 18 to 90 years with variant or wild-type ATTR-CM diagnosed within the prior 24 months.

“Acoramidis is a novel oral transthyretin (TTR) stabilizer approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) based on the phase 3 ATTRibute-CM study (ClinicalTrials.gov identifier, NCT03860935),” wrote the researchers. “As the ATTR-CM therapy landscape evolves, there is a growing need to evaluate changes in disease markers and treatment response in patients who switch therapies.”

Tafamidis and acoramidis bind the TTR tetramer and prevent its dissociation into amyloidogenic monomers. Acoramidis has been shown to achieve near-complete (≥ 90%) TTR stabilization through enthalpically driven binding. The study authors note that this mechanism may result in greater TTR stabilization than tafamidis. As more ATTR-CM therapies become available, the authors write, there is growing interest in understanding how biomarkers of treatment response change when patients switch between TTR stabilizers.

End Points and Study Procedures

Eligible participants must have received tafamidis for at least 3 months before enrollment, with documented adherence of at least 80% of days during a 21-day screening period. The day after their final tafamidis dose, participants will begin acoramidis at 712 mg twice daily, self-administered at home for 6 months. Total study participation will last up to 7.75 months, including a 30-day follow-up period.

The primary end point is the change in sTTR, measured by immunoturbidimetry, from baseline to month 6 or premature treatment discontinuation, analyzed using a 1-sided paired Wilcoxon signed-rank test. Secondary end points include sTTR levels at multiple time points; changes in cardiovascular biomarkers, including NT-proBNP, high-sensitivity troponin T, and retinol-binding protein 4; kidney biomarkers, including estimated glomerular filtration rate, creatinine, cystatin C, and urinary albumin-to-creatinine ratio; thyroid-stimulating hormone; echocardiographic measures; 6-minute walking distance; Kansas City Cardiomyopathy Questionnaire and EQ-5D-5L scores; and treatment-emergent adverse events. Exploratory objectives include direct assessment of TTR stabilization using ex vivo assays.

The rationale draws in part on findings from the open-label extension (OLE) of the pivotal ATTRibute-CM (NCT03860935) trial. Participants who had received placebo plus tafamidis during the randomized trial and subsequently switched to acoramidis in the OLE had mean sTTR increases of 3.0 mg/dL at month 1 and 3.4 mg/dL at month 6.1 The ACO-SWITCH authors note that these findings warrant prospective evaluation of sTTR changes after a direct tafamidis-to-acoramidis switch.

In the broader ATTRibute-CM OLE analysis, continuous acoramidis treatment was associated with a lower hazard of all-cause mortality or first cardiovascular hospitalization through month 42 compared with participants who switched from placebo to acoramidis at month 30.² However, these findings do not establish sTTR as a validated surrogate for clinical outcomes.

Managed Care Implications

As payers and health systems evaluate treatment selection between 2 approved oral TTR stabilizers, ACO-SWITCH is designed to generate prospective, standardized evidence on whether switching from tafamidis to acoramidis produces measurable changes in sTTR and other biomarkers. Such data could complement existing retrospective studies and open-label extension analyses, which cannot fully isolate the effects of a direct treatment switch.

The study authors acknowledge that the single-arm design limits direct comparison with continued tafamidis or acoramidis therapy and that the 6-month treatment period may not capture longer-term clinical outcomes.¹ The study also has eligibility criteria that exclude some patients with more advanced or clinically unstable disease, so its findings should not be assumed to represent the entire ATTR-CM population. Nonetheless, the investigators designed the inclusion criteria to capture a broad population of patients encountered in clinical practice.

“ACO-SWITCH is a prospective study in adults with ATTR-CM,” wrote the researchers. “The study will determine the effects of switching treatment from tafamidis to acoramidis, with a particular focus on sTTR levels. ACO-SWITCH aims to provide evidence to support clinical decision-making and guide optimal management in patients with ATTR-CM.”

References

1. Pfister R, Michel L, Schulze M, et al. ACO-SWITCH: rationale and design of a phase 4 study evaluating serum transthyretin in ATTR-CM after switching from tafamidis to acoramidis. Cardiol Ther. Published online August 20, 2026. doi:10.1007/s40119-026-00466-4
2. Judge DP, Gillmore JD, Alexander KM, et al. Long-term efficacy and safety of acoramidis in ATTR-CM: initial report from the open-label extension of the ATTRibute-CM trial. Circulation. 2025;151(8):601-611. doi:10.1161/CIRCULATIONAHA.124.072771