IMPORTANT INFORMATION FOR THE HEALTHCARE PROVIDER

The publication, Fontana M, Masri A, Solomon S, et al. Eplontersen for Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2026, describes a use of WAINUA® (eplontersen) injection, for subcutaneous use, 45 mg, that has not been approved by the FDA. WAINUA is not approved for the treatment of transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM), and the safety and effectiveness of WAINUA for ATTR-CM has not been established.

WAINUA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. WAINUA reduces serum vitamin A levels, supplementation is recommended. Potentially serious risks observed in clinical trials include atrioventricular (AV) heart block and reduced vitamin A levels, which may lead to vision problems. Please see the Important Safety Information for WAINUA below and the full US Prescribing Information for WAINUA.

AstraZeneca recommends the use of WAINUA only in accordance with its approved Prescribing Information. Prescription drugs used outside of an approved indication may not be eligible for reimbursement by third-party payors, including Medicare or Medicaid.

The CARDIO-TTRansform trial has potential limitations. The proportion of patients who were enrolled in CARDIO-TTRansform that were non-Caucasian, women, or had variant disease was low. Additionally, because TTR stabilizers were allowed as background therapy at baseline, but not randomly assigned, this trial design does not allow for a randomized comparison of the effects of eplontersen alone versus TTR stabilizers alone. Also, tafamidis was the most prevalent concomitant TTR stabilizer therapy used, which may potentially limit conclusions regarding acoramidis.

The CARDIO-TTRansform trial was supported by Ionis Pharmaceuticals and AstraZeneca. Some authors of this article were employees of, shareholders, or under contract with AstraZeneca. Some authors have received compensation from AstraZeneca. Specific details of each author’s affiliations and the nature of any relationship with AstraZeneca are available with the full text of this article at NEJM.org. Specific details of AstraZeneca’s payments to US healthcare providers can be found on https://OpenPaymentsData.cms.gov/

This information is intended for educational purposes only. By accepting this item of value, you acknowledge and agree to access the publication, which may be reported as a transfer of value in accordance with the US Physician Payments Sunshine Act. Please note: you will not be charged for this publication.

IMPORTANT INFORMATION FOR THE HEALTHCARE PROVIDER

The publications, Fontana M, Masri A, Solomon S, et al. Eplontersen for transthyretin amyloid cardiomyopathy. N Engl J Med. 2026 and García-Pavía P, Cappelli F, Davis M, et al. Eplontersen with and without background transthyretin stabilizers in transthyretin amyloid cardiomyopathy: secondary analysis of a phase 3, randomized controlled trial. Nature Medicine. 2026, describe a use of WAINUA® (eplontersen) injection, for subcutaneous use, 45 mg, that has not been approved by the FDA. WAINUA is not approved for the treatment of transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM), and the safety and effectiveness of WAINUA for ATTR-CM has not been established.

WAINUA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. WAINUA reduces serum vitamin A levels, supplementation is recommended. Potentially serious risks observed in clinical trials include atrioventricular (AV) heart block and reduced vitamin A levels, which may lead to vision problems. Please see the Important Safety Information for WAINUA below and the full US Prescribing Information for WAINUA.

AstraZeneca recommends the use of WAINUA only in accordance with its approved Prescribing Information. Prescription drugs used outside of an approved indication may not be eligible for reimbursement by third-party payors, including Medicare or Medicaid.

Study limitations:
For Fontana M, Masri A, et al, the proportion of patients who were enrolled in CARDIO-TTRansform that were non-Caucasian, women, or had variant disease was low. Additionally, because TTR stabilizers were allowed as background therapy at baseline, but not randomly assigned, this trial design does not allow for a randomized comparison of the effects of eplontersen alone versus TTR stabilizers alone. Also, tafamidis was the most prevalent concomitant TTR stabilizer therapy used, which may potentially limit conclusions regarding acoramidis.

For García-Pavía et al, first, estimation of a true monotherapy effect of eplontersen is limited by the drop-in use of stabilizers during the trial. However, this substantial drop-in use of stabilizers in patients who were not receiving them at baseline would be expected to drive the interaction towards the null and underestimate the true monotherapy effect of eplontersen. Second, the analyses of combination therapy address only the sequence of adding a gene silencer to a background stabilizer, and not vice versa. The analyses were conducted on subpopulations of the main trial, in which chance effects and residual confounding may occur due to smaller sample sizes. However, the differential effects of eplontersen according to baseline stabilizer use were consistent across multiple endpoints, making this unlikely. Lastly, tafamidis was almost the only TTR stabilizer used in this study. As such, assessment of the effects of other stabilizers such as acoramidis was not possible.

The CARDIO-TTRansform trial was supported by Ionis Pharmaceuticals and AstraZeneca. The following authors, editors, or other contributors of this article were employees of, consultants to, or received compensation from AstraZeneca or Ionis.

Fontana, M, Masri A, et al: Azevedo, O; Brice, G; Cappelli, F; Chen, J; Claggett, B; Conrad, T; Cruz, M; Damy, T; Davis, M; Follis, R; Fontana, M; Garcia-Pavia, P; Gillmore, J; Hanna, M; Khouri, M; Masri, A; Maurer, M; Obici, L; Riley, R.; Solomon, S; Sperry, B; Störk, S; Tahara, N; Tsimikas, S; Yang, Q.

Garcia-Pavia et al: Garcia-Pavia, P; Cappelli, F; Davis, M; Fontana, M, Gillmore, J; Hanna M, Masri, A; Obici, L; Solomon, S; Sperry, B; Tahara, N; Waddington-Cruz, M; Boman, K; Cuddy, S; Debonnaire, P; Fine, N; Yilmaz, A; Conrad, T; Yang, Q; Chen, J; Tsimikas, S; Maurer, M; Amato, A; Riley, R; de Klerk, S.

Specific details of AstraZeneca’s payments to US healthcare providers can be found on https://OpenPaymentsData.cms.gov/

This information is intended for educational purposes only. By accepting this item of value, you acknowledge and agree to access the publication, which may be reported as a transfer of value in accordance with the US Physician Payments Sunshine Act. Please note: you will not be charged for this publication.