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ButtonLoadingButtonLoading AboutAbout ATTR-CMUrgencySuspectDetectDiagnostic flowchartAbout ATTR-PNUrgencyAwarenessPartnershipStudy DesignStudy DesignAbout ATTR-PNUrgencyAwarenessPartnershipEfficacy & SafetyPivotal efficacyLong-term survivalSubgroup analysisKey secondary endpointsEarly efficacy measuresSafety profileATTR-PNPivotal efficacyPivotal efficacy ALTLong-term efficacyMutations efficacyLong-term survivalSafety profileDosingATTR-CM dosingATTR-PNPivotal efficacyPivotal efficacy ALTLong-term efficacyMutations efficacyLong-term survivalSafety profileMOD/MOARole of TTRATTR-CM MODATTR-CM MOAATTR-PNATTR-PN MODATTR-PN MOASupport & ResourcesMaterialsVideosATTR-PNATTR-PN MODATTR-PN MOA

Prescribing Information

ATTR-PNATTR-PN MODATTR-PN MOA

Vyndaqel 61mg is indicated for the treatment of wild‑type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy
(ATTR-CM).1

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Refer to section 4.8 of the SmPC for how to report adverse reactions.

VYNDAQEL* is the only ATTR-CM therapy with 5 years of clinical data1-3†

Prolonged survival was observed throughout ATTR-ACT and the post hoc LTE study1,3

A European Society of Cardiology Working Group position paper states that VYNDAQEL “should be generally considered the agent of choice in (hereditary and wild-type) ATTR-CM patients with reasonable expected survival.”4

ATTR-ACT Phase 3 Study 
Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT)

A phase 3, multicenter, international, randomized, double-blind, placebo-controlled study in 441 patients with wild-type or hereditary ATTR-CM.1

  • Two-thirds of patients in the pooled VYNDAQEL group were on the 80-mg dose1
  • Approval of VYNDAQEL (tafamidis) was based on ATTR-ACT, which evaluated pooled VYNDAQEL doses of 20 mg and 80 mg. A single VYNDAQEL 61-mg capsule corresponds to VYNDAQEL 80 mg (four 20-mg capsules) and is not interchangeable on a per-mg basis1,2,5 
Post hoc analysis of ATTR-ACT and LTE3|| See the bioequivalence data  Inclusion criteria1,3
  • Patients between 18 and 90 years of age
  • Confirmation of ATTR-CM, wild type or hereditary
  • Echocardiography with an end-diastolic interventricular septal wall thickness >12 mm
  • History of heart failure with at least 1 prior hospitalisation for heart failure, or clinical evidence of heart failure (without hospitalisation)#
  • NT-proBNP level ≥600 pg/mL
  • 6MWT >100 m
Manifested by signs or symptoms of volume overload or elevated intracardiac pressures requiring treatment with a diuretic for improvement; an NT-proBNP level greater than or equal to 600 pg/mL; and a 6MWT distance exceeding 100 m.1
Main exclusion criteria1,6,7
  • ​​​​​​​Heart failure unrelated to ATTR-CM
  • NYHA class IV heart failure
  • Light-chain amyloidosis
  • History of liver or heart transplantation
  • Implanted cardiac mechanical assist device6**
  • Pregnancy or breastfeeding
  • Previous VYNDAQEL treatment
  • eGFR <25 mL/min/1.73 m2
  • Liver transaminase levels >2x the upper limit of normal
  • mBMI <600
  • Concurrent treatment with NSAIDs,†† tauroursodeoxycholate, doxycycline, calcium-channel blockers, or digitalis
Cardiac mechanical assist device (CMAD) term utilized to cover LVAD. Patients with a permanent pacemaker or implanted cardiac defibrillator were permitted in this study.6Select NSAIDs were permitted (eg, aspirin, ibuprofen, naproxen).6
 The Finkelstein-Schoenfeld method1
  • A statistical method used to compare each patient to every other patient within each stratum in a pair-wise manner that proceeds in a hierarchical fashion using all-cause mortality first1
  • The test statistic is based on the sum of scores and stratified by TTR genotype (hereditary and wild type) and NYHA baseline classification, resulting in a total of 4 strata1

All-cause mortality

CV-related hospitalization‡‡

Hierarchical comparison prioritizes all-cause mortality over CV-related hospitalizations1

Frequency of CV-related hospitalizations is used to compare patients who cannot be differentiated based on all-cause mortality.
A single VYNDAQEL 61 mg capsule corresponds to VYNDAQEL 80 mg (four 20-mg capsules) and is not interchangeable on a per-mg basis.2,5ATTR-ACT was a phase 3, multicenter, international, parallel-design, placebo-controlled, double-blind, randomized study in 441 patients with wild-type or hereditary ATTR-CM. In ATTR-ACT, patients with ATTR-CM were randomized (2:1:2) to VYNDAQEL 80 mg, VYNDAQEL 20 mg, or placebo once daily (qd) for 30 months. Upon completion of ATTR-ACT, patients could enroll in the ongoing LTE study for up to 60 months. Patients receiving VYNDAQEL in ATTR-ACT continued to receive the same dose uninterrupted while those in the placebo group were randomized (2:1) to VYNDAQEL 80 mg or 20 mg. As of July 2018, the LTE protocol was amended to transition all patients to VYNDAQEL 61 mg. Patients were treated with VYNDAQEL 80 mg or 20 mg (up to the protocol amendment) for a median of 39 months. Median LTE follow-up was 58.5 months in the continuous VYNDAQEL 80 mg to 61 mg group and 57.1 months in the placebo to VYNDAQEL 80 mg/20 mg to 61 mg group. For both groups, time zero for survival analyses was the time of enrollment in ATTR-ACT.3The primary analysis was conducted using the Finkelstein-Schoenfeld method.1In this LTE post-hoc analysis, patients treated with VYNDAQEL 80 mg in ATTR-ACT continued with VYNDAQEL 80 mg, then transitioned to VYNDAQEL 61 mg and were compared with those treated with placebo in ATTR-ACT, who were randomized to VYNDAQEL 80 mg or 20 mg (2:1), then transitioned to VYNDAQEL 61 mg. The VYNDAQEL 20 mg arm in ATTR-ACT was not included in the LTE post-hoc analysis. Patients were treated with VYNDAQEL 80 mg or 20 mg (up to the protocol amendment) for a median of 39 months. Median LTE follow-up was 58.5 months in the continuous VYNDAQEL 80 mg to 61 mg group and 57.1 months in the placebo to VYNDAQEL 80 mg/20 mg to 61 mg group. For both groups, time zero for survival analyses was the time of enrollment in ATTR-ACT.3The primary efficacy outcome in the LTE was all-cause mortality, with heart transplant and implantation of a cardiac mechanical assist device treated as death. Differential all-cause mortality in the 2 groups was assessed by Cox proportional hazards model with treatment, genotype (wtATTR and hATTR), and NYHA baseline classification (NYHA classes I and II combined and NYHA class Ill) in the model. All-cause mortality was also assessed by Cox proportional hazards model by genotype and by NYHA baseline classification subgroups.3ATTR-ACT=Tafamidis in Transthyretin Cardlomyopathy Clinical Trial; ATTR-CM=tranthyretin amyloid cardiomyopathy; LTE=long-term extension; eGFR=estimated glomerular filtration rate; LVAD=left ventricular assist device; mBMl=modified body mass index; NT-proBNP=N-terminal pro-B-type natriuretic peptide; NSAID=nonsteroidal anti-inflammatory drug; NYHA=New York Heart Association; hATTR=hereditary transthyretin amyloidosis; wtATTR=wild-type transthyretin amyloidosis.
Explore More ATTR-CM efficacy See the Pivotal Efficacy Data
ATTR-CM identification and diagnosis Download Resources
References:Maurer MS, Schwartz JH, Gundapaneni B, et al; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016. doi:10.1056/NEJMoa1805689VYNDAQEL summary of product characteristicsElliott P, Drachman BM, Gottlieb SS, et al. Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy. Circ Heart Fail. 2022;153e008193:1-8.Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42(16):1554-1568. doi:10.1093/eurheartj/ehab072Lockwood PA, Le VH, O'Gorman MT, et al. The bioequivalence of tafamidis 61 mg free acid capsules and tafamidis meglumine 4 × 20-mg capsules in healthy volunteers. Clin Pharmacol Drug Dev. 2020;9(7):849-854. doi:10.1002/cpdd.789Maurer MS, Schwartz JH, Gundapaneni B, et al; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy [protocol]. N Engl J Med. 2018;379(11):1007-1016. Accessed July 6, 2020. https://nejm.org/doi/suppl/10.1056/NEJMoa1805689/suppl_file/nejmoa1805689_protocol.pdfMaurer MS, Schwartz JH, Gundapaneni B, et al; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretinamyloid cardiomyopathy [supplemental appendix]. N Engl J Med. 2018;379(11):1007-1016. Accessed July 6, 2020. https://nejm.org/doi/suppl/10.1056/NEJMoa1805689/suppl_file/nejmoa1805689_appendix.pdf VYNDAQEL Prescribing InformationLoading
Study Design

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