Staying Ahead of the Curve in ATTR-CM: Adapting and Advancing Our Approach to Decision-Making as the Treatment Landscape Evolves
PeerVoice
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Oct 28, 2025
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About This Presentation
Emer Joyce, MB BCh BAO, PhD, Carsten Tschöpe, MD, PhD, and Peter van der Meer, MD, PhD, discuss ATTR-CM in this IME activity titled "Staying Ahead of the Curve in ATTR-CM: Adapting and Advancing Our Approach to Decision-Making as the Treatment Landscape Evolves." For the full presentation...
Slide Content
PeerVoice
Staying Ahead of the Curve in ATTR-CM: Adapting and Advancing Our
Approach to Decision-Making as the Treatment Landscape Evolves
Learning Objectives
Assess available data which may be applied to guide treatment decision-making
within the evolving treatment landscape of transthyretin amyloid cardiomyopathy
(ATTR-CM)
Differentiate between TTR stabilisers based on existing evidence in ATTR-CM
Apply current evidence related to the use of combination therapy in patients with
ATTR-CM
This activity is supported by an unrestricted educational grant from Bayer HealthCare Pharmaceuticals Inc. Bayer has had
no involvement in the selection of the speakers, the development of the activity, the agenda, or the materials.
www.peervoice.com/FMW870 Copyright © 2010-2025, Pe
Staying Ahead of the Curve in ATTR-CM: Adapting and Advancing Our
Approach to Decision-Making as the Treatment Landscape Evolves
Learning Objectives
Assess available data which may be applied to guide treatment decision-making
within the evolving treatment landscape of transthyretin amyloid cardiomyopathy
(ATTR-CM)
Differentiate between TTR stabilisers based on existing evidence in ATTR-CM
Apply current evidence related to the use of combination therapy in patients with
ATTR-CM
This activity is supported by an unrestricted educational grant from Bayer HealthCare Pharmaceuticals Inc. Bayer has had
no involvement in the selection of the speakers, the development of the activity, the agenda, or the materials.
www.peervoice.com/FMW870 Copyright © 2010-2025, Pe
PeerVoice
Part 1 of 4: Preparing for the Future in ATTR-CM: How Will We Apply What
We've Learned to Optimise Patient Experiences and Outcomes?
Emer Joyce, MB BCh BAO, PhD Carsten Tschöpe, MD, PhD
University College Dublin Deutsches Herzzentrum der Charite
Mater University Hospital Berlin, Germany
Dublin, Ireland
Peter van der Meer, MD, PhD
University Medical Center Groningen
Groningen, The Netherlands
Copyright © 2010-2025, PeerVoice
Part 1 of 4: Preparing for the Future in ATTR-CM: How Will We Apply What
We've Learned to Optimise Patient Experiences and Outcomes?
Emer Joyce, MB BCh BAO, PhD Carsten Tschöpe, MD, PhD
University College Dublin Deutsches Herzzentrum der Charite
Mater University Hospital Berlin, Germany
Dublin, Ireland
Peter van der Meer, MD, PhD
University Medical Center Groningen
Groningen, The Netherlands
Copyright © 2010-2025, PeerVoice
PeerVoice
Emer Joyce, MB BCh BAO, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Honoraria from Alnylam Pharmaceuticals, Inc.
layer AG; and Pfizer Inc.
Carsten Tschöpe, MD, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Speaker fee from AstraZeneca; Bayer AG; and Novartis AG.
Peter van der Meer, MD, PhD, has no financial interests/relationships or affiliations in relation to this
activity.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
Emer Joyce, MB BCh BAO, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Honoraria from Alnylam Pharmaceuticals, Inc.
layer AG; and Pfizer Inc.
Carsten Tschöpe, MD, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Speaker fee from AstraZeneca; Bayer AG; and Novartis AG.
Peter van der Meer, MD, PhD, has no financial interests/relationships or affiliations in relation to this
activity.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
Overview of Key ATTR-CM Trials
ATTR-ACT
Tafamidis
(Phase 3, n = 264)
Age (+ SD) or (range), y 745 =72
ATTRWt (%) 761
NYHA class, %
Class | ea
Class I 614
Class ill 295
NT-proBNP cut-off 2600 pg/mL
eGFR cut-off <25 mL/min/173m?
SMWT cut-off >100 m
Hierarchical: all-cause mortality
Primary endpoint and CV hospitalisations
‘at 30 mo
Follow-up 30 mo
Concomitant therapy N/A
Hierarchical combo of mortality,
CV hospitalisations, NT-proBNP,
‘6MWT at 30 mo
Tafamidis allowed after 12 mo
HELIOS-B
Vutrisiran
326)
714 265 710 (45-85)
903 89
121 5
696 7
183 8
>800 pg/ml (or »600 pg/ml. for
2300 palm patients with AF)
5 mL/min/L 73m? <30 mL/min/173m?
2150m 2150 m
Composite: all-cause mortality
and recurrent CV events at
33-36 mo (total and
monotherapy subgroups)
Variable (33-36 mo)
Tafamidis allowed at BL
30 mo
ients with an eGFR <30 m/min/173m* were excluded from the primary efficacy analysis but were included in an exploratory safety analysis.
Note: The data shown are not derived from head-to-head trials and should be interpreted with caution.
www.peervoice.com/FMW870
Copyright © 2010-2025, Peer
Overview of Key ATTR-CM Trials
ATTR-ACT
Tafamidis
(Phase 3, n = 264)
Age (+ SD) or (range), y 745 =72
ATTRWt (%) 761
NYHA class, %
Class | ea
Class I 614
Class ill 295
NT-proBNP cut-off 2600 pg/mL
eGFR cut-off <25 mL/min/173m?
SMWT cut-off >100 m
Hierarchical: all-cause mortality
Primary endpoint and CV hospitalisations
‘at 30 mo
Follow-up 30 mo
Concomitant therapy N/A
Hierarchical combo of mortality,
CV hospitalisations, NT-proBNP,
‘6MWT at 30 mo
Tafamidis allowed after 12 mo
HELIOS-B
Vutrisiran
326)
714 265 710 (45-85)
903 89
121 5
696 7
183 8
>800 pg/ml (or »600 pg/ml. for
2300 palm patients with AF)
5 mL/min/L 73m? <30 mL/min/173m?
2150m 2150 m
Composite: all-cause mortality
and recurrent CV events at
33-36 mo (total and
monotherapy subgroups)
Variable (33-36 mo)
Tafamidis allowed at BL
30 mo
ients with an eGFR <30 m/min/173m* were excluded from the primary efficacy analysis but were included in an exploratory safety analysis.
Note: The data shown are not derived from head-to-head trials and should be interpreted with caution.
www.peervoice.com/FMW870
Copyright © 2010-2025, Peer
PeerVoice
ATTR-CM Trials: All-Cause Mortality
ATTR-ACT
— Pooled tafamidi
Sa =
Zu Placebo
À | pomenccson
Ce er ee ee E E E ES
Ter See Dose me
HELIOS-B: Overall Population
®
é
0 6 D où om 0 % #4
Time Since First Dose, mo
‘Cumulative incidence, %
ATTRibute-CM
= .
4 Acoramiis
: n= 409
Time Since Randomisation, mo
HELIOS-B: Monotherapy Population
Patients Alive, %
mm 088 (6x 1044-097)
Time Since First Dose, mo
Note: The data shown are not derived from head-to-head trials and should be interpreted with caution.
www.peervoice.com/FMW870
Copyright © 2010-2025, PeerVoice
ATTR-CM Trials: All-Cause Mortality
ATTR-ACT
— Pooled tafamidi
Sa =
Zu Placebo
À | pomenccson
Ce er ee ee E E E ES
Ter See Dose me
HELIOS-B: Overall Population
®
é
0 6 D où om 0 % #4
Time Since First Dose, mo
‘Cumulative incidence, %
ATTRibute-CM
= .
4 Acoramiis
: n= 409
Time Since Randomisation, mo
HELIOS-B: Monotherapy Population
Patients Alive, %
mm 088 (6x 1044-097)
Time Since First Dose, mo
Note: The data shown are not derived from head-to-head trials and should be interpreted with caution.
www.peervoice.com/FMW870
Copyright © 2010-2025, PeerVoice
PeerVoice
ATTR-CM Approved Therapies: Administration and Dose
Administration
Route
Posology
61mg QD
Additional
Considerations
Acoramidis
Vutrisiran
Oral (free acid capsule) =
712 mg BID _
Chel (356 mg x 2 tablets)
Vitamin A
Subcutaneous tone a nen) supplementation is
Bern advised
Copyright © 2010-2025, PeerVoice
ATTR-CM Approved Therapies: Administration and Dose
Administration
Route
Posology
61mg QD
Additional
Considerations
Acoramidis
Vutrisiran
Oral (free acid capsule) =
712 mg BID _
Chel (356 mg x 2 tablets)
Vitamin A
Subcutaneous tone a nen) supplementation is
Bern advised
Copyright © 2010-2025, PeerVoice
PeerVoice
ATTR-CM: Traditional Indicators of Disease Progression
Expert Consensus-Based Indicators (2021)
r
Clinical and functional Laboratory biomarker Imaging and ECG
Increase in HF-related
hospitalisation
Increase in NYHA Class
KCCQ (5-10
Bene
decline in 6MWT
‘every 6 months.
¡e marker from each domain provides the minimum requiremen
for assessing ATT M progression
Copyright © 2010-2025, PeerVoice
ATTR-CM: Traditional Indicators of Disease Progression
Expert Consensus-Based Indicators (2021)
r
Clinical and functional Laboratory biomarker Imaging and ECG
Increase in HF-related
hospitalisation
Increase in NYHA Class
KCCQ (5-10
Bene
decline in 6MWT
‘every 6 months.
¡e marker from each domain provides the minimum requiremen
for assessing ATT M progression
Copyright © 2010-2025, PeerVoice
PeerVoice
ATTR-CM: Novel Indicators of Disease Progression
Recently Proposed Indicators (2025)
Markers
NT-proBNP NT-proBNP progression defined as an increase of >700 ng/L and >30%
Outpatient diuretic intensification defined as any initiation
LEE ESS or increment in the dose of loop diuretic
Absolute reduction defined as a >35 m decrease;
Shui distance relative reduction defined as a 5% decrease
KCCQ Worsening of the KCCQ
Mitral regurgitation Worsening of mitral regurgitation
Tricuspid regurgitation Worsening of tricuspid regurgitation
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
ATTR-CM: Novel Indicators of Disease Progression
Recently Proposed Indicators (2025)
Markers
NT-proBNP NT-proBNP progression defined as an increase of >700 ng/L and >30%
Outpatient diuretic intensification defined as any initiation
LEE ESS or increment in the dose of loop diuretic
Absolute reduction defined as a >35 m decrease;
Shui distance relative reduction defined as a 5% decrease
KCCQ Worsening of the KCCQ
Mitral regurgitation Worsening of mitral regurgitation
Tricuspid regurgitation Worsening of tricuspid regurgitation
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PeerVoice
Abbreviations and References
Overview of Key ATTR-CM Trials
Abbreviation(s): 6MWT: 6-minute walk test; AF: atrial fibrillation; ATTR-CM: transthyretin amyloid (ATTR)
cardiomyopathy; BL: baseline; CV: cardiovascular; eGFR: estimated glomerular filtration rate; NT-proBNP: N-terminal
pro-B-type natriuretic peptide; NYHA: New York Heart Association; SD: standard deviation; wt: wild type.
Reference(s): Maurer MS; ATTR-ACT Study Investigators. N Engl J Med. 2018:379:1007-1016.
Gillmore JD; ATTRibute-CM Investigators. N Engl J Med. 2024;390:132-142.
Fontana M; HELIOS-B Trial Investigators and Collaborators. N Engl J Med. 2025:392:33-44.
ATTR-CM Trials: All-Cause Mortality
Reference(s): Maurer MS; ATTR-ACT Study Investigators. N Eng! J Med. 2018;379:1007-1016.
Gillmore JD; ATTRibute-CM Investigators. N Engl J Med. 2024;390:132-142.
Fontana M; HELIOS-B Trial Investigators and Collaborators. N Engl J Med. 2025:392:33-44.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVaice
Abbreviations and References
Overview of Key ATTR-CM Trials
Abbreviation(s): 6MWT: 6-minute walk test; AF: atrial fibrillation; ATTR-CM: transthyretin amyloid (ATTR)
cardiomyopathy; BL: baseline; CV: cardiovascular; eGFR: estimated glomerular filtration rate; NT-proBNP: N-terminal
pro-B-type natriuretic peptide; NYHA: New York Heart Association; SD: standard deviation; wt: wild type.
Reference(s): Maurer MS; ATTR-ACT Study Investigators. N Engl J Med. 2018:379:1007-1016.
Gillmore JD; ATTRibute-CM Investigators. N Engl J Med. 2024;390:132-142.
Fontana M; HELIOS-B Trial Investigators and Collaborators. N Engl J Med. 2025:392:33-44.
ATTR-CM Trials: All-Cause Mortality
Reference(s): Maurer MS; ATTR-ACT Study Investigators. N Eng! J Med. 2018;379:1007-1016.
Gillmore JD; ATTRibute-CM Investigators. N Engl J Med. 2024;390:132-142.
Fontana M; HELIOS-B Trial Investigators and Collaborators. N Engl J Med. 2025:392:33-44.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVaice
PeerVoice
Abbreviations and References (Cont'd)
ATTR-CM Approved Therapies: Administration and Dose
Abbreviation(s): BID: twice daily; Q3M: every 3 months; QD: once daily.
Reference(s): Acoramidis Summary of Product Characteristics (SmPC). European Medicines Agency (EMA) website.
https://www.ema.europa.eu/en/documents/product-information/beyonttra-epar-product-information_en.pdf.
Accessed 8 October 2025.
Tafamidis SmPC. EMA website. https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar=
product-information_enpdf. Accessed 8 October 2025.
Vutrisiran SmPC. EMA website. https://www.ema.europa.eu/en/documents/product-information/amvuttra-epar-
product-information_enpdf. Accessed 8 October 2025.
ATTR-CM: Traditional Indicators of Disease Progression
Abbreviation(s): EQ-5D: EuroQol 5 Dimensions; GLS: global longitudinal strain; HF: heart failure; KCCQ: Kansas City
Cardiomyopathy Questionnaire; LVEF: left ventricular (LV) ejection fraction; NAC: National Amyloidosis Centre;
QoL: quality of life.
Reference(s): Garcia-Pavia P et al. Eur J Heart Fail. 2021:23:895-905.
ATTR-CM: Novel Indicators of Disease Progression
Reference(s): Fontana M et al. JACC Cardiovasc Imaging. 2025:
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
Abbreviations and References (Cont'd)
ATTR-CM Approved Therapies: Administration and Dose
Abbreviation(s): BID: twice daily; Q3M: every 3 months; QD: once daily.
Reference(s): Acoramidis Summary of Product Characteristics (SmPC). European Medicines Agency (EMA) website.
https://www.ema.europa.eu/en/documents/product-information/beyonttra-epar-product-information_en.pdf.
Accessed 8 October 2025.
Tafamidis SmPC. EMA website. https://www.ema.europa.eu/en/documents/product-information/vyndaqel-epar=
product-information_enpdf. Accessed 8 October 2025.
Vutrisiran SmPC. EMA website. https://www.ema.europa.eu/en/documents/product-information/amvuttra-epar-
product-information_enpdf. Accessed 8 October 2025.
ATTR-CM: Traditional Indicators of Disease Progression
Abbreviation(s): EQ-5D: EuroQol 5 Dimensions; GLS: global longitudinal strain; HF: heart failure; KCCQ: Kansas City
Cardiomyopathy Questionnaire; LVEF: left ventricular (LV) ejection fraction; NAC: National Amyloidosis Centre;
QoL: quality of life.
Reference(s): Garcia-Pavia P et al. Eur J Heart Fail. 2021:23:895-905.
ATTR-CM: Novel Indicators of Disease Progression
Reference(s): Fontana M et al. JACC Cardiovasc Imaging. 2025:
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PeerVoice
Part 2 of 4: Differentiating Between TTR Stabilisers for ATTR-CM:
What Data Is Available to Guide Our Decision-Making?
iid?
Emer Joyce, MB BCh BAO, PhD Carsten Tschôpe, MD, PhD
University College Dublin Deutsches Herzzentrum der Charite
Mater University Hospital Berlin, Germany
Dublin, Ireland
Peter van der Meer, MD, PhD
University Medical Center Groningen
Groningen, The Netherlands
Copyright © 2010-2025, PeerVoice
Part 2 of 4: Differentiating Between TTR Stabilisers for ATTR-CM:
What Data Is Available to Guide Our Decision-Making?
iid?
Emer Joyce, MB BCh BAO, PhD Carsten Tschôpe, MD, PhD
University College Dublin Deutsches Herzzentrum der Charite
Mater University Hospital Berlin, Germany
Dublin, Ireland
Peter van der Meer, MD, PhD
University Medical Center Groningen
Groningen, The Netherlands
Copyright © 2010-2025, PeerVoice
PeerVoice
Emer Joyce, MB BCh BAO, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Honoraria from Alnylam Pharmaceuticals, Inc.
layer AG; and Pfizer Inc.
Carsten Tschöpe, MD, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Speaker fee from AstraZeneca; Bayer AG; and Novartis AG.
Peter van der Meer, MD, PhD, has no financial interests/relationships or affiliations in relation to this
activity.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
Emer Joyce, MB BCh BAO, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Honoraria from Alnylam Pharmaceuticals, Inc.
layer AG; and Pfizer Inc.
Carsten Tschöpe, MD, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Speaker fee from AstraZeneca; Bayer AG; and Novartis AG.
Peter van der Meer, MD, PhD, has no financial interests/relationships or affiliations in relation to this
activity.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
ATTR-ACT and ATTRibute-CM Trials
ATTR-ACT ATTRibuto:
(n = 264) (n= 421)
Compound Tatamidis Acoramidis
E Promotes hydrogen bonding between the hydroxyl
pisos Sree eee oe groups of adjacent serine residues
A Y Invasive and non-invasive diagnosis
Y Invasive diagnosis
NT-proBNP »300 and «8500 pg/mL.
Inclusion criteria E MIEPrOBNE 2000 pedo. reed
Y eGFR >30 mL/min/173m? en
Y EMWT 100m + Tafamidis permitted after the initial 12 mo
Age SD). y. 7447 7787
Gender, % males EX 802
Race, % Black 143 47
ATREA 761 903
NYHA class, %
NYHAI où
NYHA II 614
NVHA I 295
NT-proBNP, ng/t 3161 (1864-4825) 2326 (1278-3910)
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ATTR-ACT and ATTRibute-CM Trials
ATTR-ACT ATTRibuto:
(n = 264) (n= 421)
Compound Tatamidis Acoramidis
E Promotes hydrogen bonding between the hydroxyl
pisos Sree eee oe groups of adjacent serine residues
A Y Invasive and non-invasive diagnosis
Y Invasive diagnosis
NT-proBNP »300 and «8500 pg/mL.
Inclusion criteria E MIEPrOBNE 2000 pedo. reed
Y eGFR >30 mL/min/173m? en
Y EMWT 100m + Tafamidis permitted after the initial 12 mo
Age SD). y. 7447 7787
Gender, % males EX 802
Race, % Black 143 47
ATREA 761 903
NYHA class, %
NYHAI où
NYHA II 614
NVHA I 295
NT-proBNP, ng/t 3161 (1864-4825) 2326 (1278-3910)
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PeerVoice
TTR Stabilisation in Vitro: Acoramidis vs Tafamidis
TTR Detection by Western Blot
% Stabilisation by Variant
E89Q £929 VOL V2
£
EA
ES
o
G6S A25S V3OM A36D 42D SS50R T6OA I68L
mm Tafamidis, 26 uM a Tafamidis, 16 uM
mm Acoramidis, 10 uM
"SD is only shown for conditions with two or more samples.
Copyright © 2010-2025, PeerVoice
www.peervoice.com/FMW870
TTR Stabilisation in Vitro: Acoramidis vs Tafamidis
TTR Detection by Western Blot
% Stabilisation by Variant
E89Q £929 VOL V2
£
EA
ES
o
G6S A25S V3OM A36D 42D SS50R T6OA I68L
mm Tafamidis, 26 uM a Tafamidis, 16 uM
mm Acoramidis, 10 uM
"SD is only shown for conditions with two or more samples.
Copyright © 2010-2025, PeerVoice
www.peervoice.com/FMW870
PeerVoice
ATTRibute-CM: sTTR and Survival Outcomes
Change From Baseline in sTTR Levels Survival by Baseline sTTR Level Through
Through Month 30 Month 30 in the Overall Population
Acoramidis
5 n=372 1 STTR 220 mad.
Tafamidis treatment ge ne
TTR «20 meat.
x ns 133,
permitted after M12
Mean Change From BL
in sTTR, mg/dl. (= SE)
Survival Probability
8
cowie Of M9 M6 M9 ME MS MO Mr M0
EL M3 MG MO M2 MIS Mia M21 M24 M27 MIO
Time, mo. Time, mo
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ATTRibute-CM: sTTR and Survival Outcomes
Change From Baseline in sTTR Levels Survival by Baseline sTTR Level Through
Through Month 30 Month 30 in the Overall Population
Acoramidis
5 n=372 1 STTR 220 mad.
Tafamidis treatment ge ne
TTR «20 meat.
x ns 133,
permitted after M12
Mean Change From BL
in sTTR, mg/dl. (= SE)
Survival Probability
8
cowie Of M9 M6 M9 ME MS MO Mr M0
EL M3 MG MO M2 MIS Mia M21 M24 M27 MIO
Time, mo. Time, mo
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ATTR-ACT and ATTRibute-CM: Open-Label Extension Survival
‘Survival Probability
3
o
ATTR-ACT
Continuous atomic
Placebo to tatami
ne
© 3 6 9 1215 18 2124 27 30 53 36 90 42 45 48 51 54 57 60 83 66 69 72
Time to Event, mo
‘Survival Probability
os
os
oa
02
ATTRibute-CM
Continous acoramicio
‘n= 409
CRRTETTEPTETETTI
Time Since Randomisation, mo
M
follow-up
+ Placebo to t
continuous tafamidis: 58.5 mo (HR, O.
midis: 57. mo
Ali
mortality
(98% Cl, 0.44-0.791: P <001)
* Continuous tafamidis: 79 (44.9%)
lacebo to tafamidis: 11 (62.7%)
Note: The data shown are not derived from head-to-head tials and should be interpreted with caution.
www.peervoice.com/FMW870
GVM through month 42
(HR, 056 [95% CL 0389-0791); P = 001)
+ Continuous acoramidis: 68 (16.6%)
+ Placebo to acoramidis: 58 (28.7%)
+ Relative risk reduction: 421%
Copyright © 2010-2025, PeerVoice
ATTR-ACT and ATTRibute-CM: Open-Label Extension Survival
‘Survival Probability
3
o
ATTR-ACT
Continuous atomic
Placebo to tatami
ne
© 3 6 9 1215 18 2124 27 30 53 36 90 42 45 48 51 54 57 60 83 66 69 72
Time to Event, mo
‘Survival Probability
os
os
oa
02
ATTRibute-CM
Continous acoramicio
‘n= 409
CRRTETTEPTETETTI
Time Since Randomisation, mo
M
follow-up
+ Placebo to t
continuous tafamidis: 58.5 mo (HR, O.
midis: 57. mo
Ali
mortality
(98% Cl, 0.44-0.791: P <001)
* Continuous tafamidis: 79 (44.9%)
lacebo to tafamidis: 11 (62.7%)
Note: The data shown are not derived from head-to-head tials and should be interpreted with caution.
www.peervoice.com/FMW870
GVM through month 42
(HR, 056 [95% CL 0389-0791); P = 001)
+ Continuous acoramidis: 68 (16.6%)
+ Placebo to acoramidis: 58 (28.7%)
+ Relative risk reduction: 421%
Copyright © 2010-2025, PeerVoice
PeerVoice
ATTR-ACT and ATTRibute-CM: Time to First Hospitalisation
ATTR-ACT ATTRibute-CM
Time to First CV Hospitalisation Time to First CV Hospitalisation
>
1 2
€ Be Acoramiis
2 08 3 n= 409
8 Poole atome À
coed tata
Eos ES
3 oa go
¿ 5
5 oa a
MR 0706 (8 CL 001-1020) ne Inka n2202
o T T T T T T T T T T 1 04 “| P=.0008
0 3 6 9 251 2124 27 20 33 Tr ar u al
Time From First Dose, mo Time Since Randomisation, mo
Note: The data shown are not derived from head-to-head trials and should be interpreted with caution.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
ATTR-ACT and ATTRibute-CM: Time to First Hospitalisation
ATTR-ACT ATTRibute-CM
Time to First CV Hospitalisation Time to First CV Hospitalisation
>
1 2
€ Be Acoramiis
2 08 3 n= 409
8 Poole atome À
coed tata
Eos ES
3 oa go
¿ 5
5 oa a
MR 0706 (8 CL 001-1020) ne Inka n2202
o T T T T T T T T T T 1 04 “| P=.0008
0 3 6 9 251 2124 27 20 33 Tr ar u al
Time From First Dose, mo Time Since Randomisation, mo
Note: The data shown are not derived from head-to-head trials and should be interpreted with caution.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
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Abbreviations and References
ATTR-ACT and ATTRibute-CM Trials
Abbreviation(s): GMWT: 6-minute walking test; ATTR-CM: transthyretin (TTR) amyloid cardiomyopathy; ATTRwt: ATTR
wild-type; eGFR: estimated glomerular filtration rate; MoA: mechanism of action; NT-proBNP: N-terminal pro-B-type
i NYHA: New York Heart Associ
Reference(s): Maurer MS; ATTR-ACT Study Investigators. N Eng! J Med. 2018:379:1007-1016.
Gilmore JD; ATTRibute-CM investigators. N Engl J Med. 2024,390:132-142.
Gonzalez-Lopez E et al. Eur Heart J. 2025;46:999-1013.
TTR Stabilisation in Vitro: Acoramidis vs Tafamidis
Abbreviation(s): SD: standard deviation.
Reference(s): Alexander K et al. European Society of Cardiology Congress 2025 (ESC 2025). Acoramidis reduces
cardiovascular mortality (CVM): Results at month 42 from the ATTRibute-CM open-label extension (OLE) study.
ATTRibute-CM: sTTR and Survival Outcomes
Abbreviation(s): SE: standard error; TTR: serum TTR.
Reference(s): Maurer MS et al. J Am Coll Cardiol. 2025:85:1911-1923.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
Abbreviations and References
ATTR-ACT and ATTRibute-CM Trials
Abbreviation(s): GMWT: 6-minute walking test; ATTR-CM: transthyretin (TTR) amyloid cardiomyopathy; ATTRwt: ATTR
wild-type; eGFR: estimated glomerular filtration rate; MoA: mechanism of action; NT-proBNP: N-terminal pro-B-type
i NYHA: New York Heart Associ
Reference(s): Maurer MS; ATTR-ACT Study Investigators. N Eng! J Med. 2018:379:1007-1016.
Gilmore JD; ATTRibute-CM investigators. N Engl J Med. 2024,390:132-142.
Gonzalez-Lopez E et al. Eur Heart J. 2025;46:999-1013.
TTR Stabilisation in Vitro: Acoramidis vs Tafamidis
Abbreviation(s): SD: standard deviation.
Reference(s): Alexander K et al. European Society of Cardiology Congress 2025 (ESC 2025). Acoramidis reduces
cardiovascular mortality (CVM): Results at month 42 from the ATTRibute-CM open-label extension (OLE) study.
ATTRibute-CM: sTTR and Survival Outcomes
Abbreviation(s): SE: standard error; TTR: serum TTR.
Reference(s): Maurer MS et al. J Am Coll Cardiol. 2025:85:1911-1923.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
Abbreviations and References (Cont'd)
ATTR-ACT and ATTRibute-CM: Open-Label Extension Survival
Abbreviation(s): CVM: cardiovascular (CV) mortality.
Reference(s): Elliott P et al. Circ Heart Fail. 2022;16:e008193.
Alexander K et al. ESC 2025. Acoramidis reduces cardiovascular mortality (CVM): Results at month 42 from the
ATTRibute-CM open-label extension (OLE) study.
lisation
ATTR-ACT and ATTRibute-CM: Time to First Hospi
Reference(s): Maurer MS; ATTR-ACT Study Investigators. N Engl J Med. 2018;379:1007-1016.
Judge DP et al. J Am Coll Cardiol. 2025;85:1003-1014.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
Abbreviations and References (Cont'd)
ATTR-ACT and ATTRibute-CM: Open-Label Extension Survival
Abbreviation(s): CVM: cardiovascular (CV) mortality.
Reference(s): Elliott P et al. Circ Heart Fail. 2022;16:e008193.
Alexander K et al. ESC 2025. Acoramidis reduces cardiovascular mortality (CVM): Results at month 42 from the
ATTRibute-CM open-label extension (OLE) study.
lisation
ATTR-ACT and ATTRibute-CM: Time to First Hospi
Reference(s): Maurer MS; ATTR-ACT Study Investigators. N Engl J Med. 2018;379:1007-1016.
Judge DP et al. J Am Coll Cardiol. 2025;85:1003-1014.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
Part 3 of 4: Considering Combination Therapy for ATTR-CM:
Will It Have a Role in Contemporary Care?
Emer Joyce, MB BCh BAO, PhD Carsten Tschópe, MD, PhD Peter van der Meer, MD, PhD
University College Dublin Deutsches Herzzentrum der Charite University Medical Center Groningen
Mater University Hospital Berlin, Germany Groningen, The Netherlands
Dublin, Ireland
Copyright © 2010-2025, PeerVoice
Part 3 of 4: Considering Combination Therapy for ATTR-CM:
Will It Have a Role in Contemporary Care?
Emer Joyce, MB BCh BAO, PhD Carsten Tschópe, MD, PhD Peter van der Meer, MD, PhD
University College Dublin Deutsches Herzzentrum der Charite University Medical Center Groningen
Mater University Hospital Berlin, Germany Groningen, The Netherlands
Dublin, Ireland
Copyright © 2010-2025, PeerVoice
PeerVoice
Emer Joyce, MB BCh BAO, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Honoraria from Alnylam Pharmaceuticals, Inc.
layer AG; and Pfizer Inc.
Carsten Tschöpe, MD, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Speaker fee from AstraZeneca; Bayer AG; and Novartis AG.
Peter van der Meer, MD, PhD, has no financial interests/relationships or affiliations in relation to this
activity.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
Emer Joyce, MB BCh BAO, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Honoraria from Alnylam Pharmaceuticals, Inc.
layer AG; and Pfizer Inc.
Carsten Tschöpe, MD, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Speaker fee from AstraZeneca; Bayer AG; and Novartis AG.
Peter van der Meer, MD, PhD, has no financial interests/relationships or affiliations in relation to this
activity.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
Combination Therapies in ATTR-CM
Participants With Participants With
Multiple Specific
Tafamidis,n(%) | Therapies, n (%)
Number of Comi
Participants Therapy Allowed
632 mm
ATTRibute-CM (611 primary Aras + 107 (17.5) 61(14.9)
analysis)
ae Patisiran +
APOLLO-B (359 efficacy and ‘eatarnicl 99 (27.6) 51 (14.2)
safety analyses) ara mudle:
Vutrisiran +
HELIOS-B 655 ee 345 (62.7) 174 (266)
CARDIO- Eplontersen + ae
TTRansform u tafamidis Ne, limit CH
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVaice
Combination Therapies in ATTR-CM
Participants With Participants With
Multiple Specific
Tafamidis,n(%) | Therapies, n (%)
Number of Comi
Participants Therapy Allowed
632 mm
ATTRibute-CM (611 primary Aras + 107 (17.5) 61(14.9)
analysis)
ae Patisiran +
APOLLO-B (359 efficacy and ‘eatarnicl 99 (27.6) 51 (14.2)
safety analyses) ara mudle:
Vutrisiran +
HELIOS-B 655 ee 345 (62.7) 174 (266)
CARDIO- Eplontersen + ae
TTRansform u tafamidis Ne, limit CH
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVaice
PeerVoice
HELIOS-B: Effect of Vutrisiran vs Placebo on CV Outcomes
orto Your (8)
mac pame
rr popttion mesas wo) 20 2 200639 210049) En 073 (06-08) ca
onemnerapy popunon won UR 165 206707) 3058(626) o 066(023-086) <a
sine tlomiis subgroup 4060) 660057) AO 26640060 =. 083 (0011 2
respeten
Ouen population wo moss) m ma mom 7805(695) . 075(062-099 ca
Monoterapy papuston CET 19 sags(isse) susu —— 66 (0-086) ca
aseo items subgroup 446338) 0) m 8 man 320467) —— (089(085-12) as
HE hospitatestions
vel puttin A] wos uns) . 087(052-036) <a
Monter popution 4009 m eo m ma sas (use) . (082(046-0.88) «a
Basen tolomii subgroup ODO) SS 62872000) 8981807) =. ‘075(040-14) 8
Urgent vis
vera population men an 2 3 2ousm a700x) . 054(030-098) ot
oneterapy popuaton 569 00) ” m 2a) s2s(ess) st O2 (040-L62) s
Dissen A 8062) 4 D UO(os anse) oo) »
Br hspitaisaions
ral puttin my nes 30 3¢ 006) 1980735) oo. ss
Monotheropy pepustion wen — 20000 ” m 303 amtasm oma a
ases tatami bro DU) NUS) 3 Ban 47200018) CS ose (oe-207) a
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
HELIOS-B: Effect of Vutrisiran vs Placebo on CV Outcomes
orto Your (8)
mac pame
rr popttion mesas wo) 20 2 200639 210049) En 073 (06-08) ca
onemnerapy popunon won UR 165 206707) 3058(626) o 066(023-086) <a
sine tlomiis subgroup 4060) 660057) AO 26640060 =. 083 (0011 2
respeten
Ouen population wo moss) m ma mom 7805(695) . 075(062-099 ca
Monoterapy papuston CET 19 sags(isse) susu —— 66 (0-086) ca
aseo items subgroup 446338) 0) m 8 man 320467) —— (089(085-12) as
HE hospitatestions
vel puttin A] wos uns) . 087(052-036) <a
Monter popution 4009 m eo m ma sas (use) . (082(046-0.88) «a
Basen tolomii subgroup ODO) SS 62872000) 8981807) =. ‘075(040-14) 8
Urgent vis
vera population men an 2 3 2ousm a700x) . 054(030-098) ot
oneterapy popuaton 569 00) ” m 2a) s2s(ess) st O2 (040-L62) s
Dissen A 8062) 4 D UO(os anse) oo) »
Br hspitaisaions
ral puttin my nes 30 3¢ 006) 1980735) oo. ss
Monotheropy pepustion wen — 20000 ” m 303 amtasm oma a
ases tatami bro DU) NUS) 3 Ban 47200018) CS ose (oe-207) a
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
SGLT2i Use in ATTR-CM: Study Findings
Data of 2,356 consecutive SGLT2i Use
patients with ATTR-CM
analysed
(2014-2022) Attenuated rise in NYHA
functional class
Attenuated rise in NT-proBNP
Slower decline in eGFR
Lower loop diuretic requirement
Stable BP profile
Propensity score
matching 1:1 using
16 variables
Over 28 months, lower:
Untreated
Treated with propensity- + All-cause mortality
SGLT2i matched . Qu
(n= 220) Ces, + Composite CV mortality and HHF
Note: SGLT2i therapy was associated with a 4.5% discontinuation rate over 28 months.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
SGLT2i Use in ATTR-CM: Study Findings
Data of 2,356 consecutive SGLT2i Use
patients with ATTR-CM
analysed
(2014-2022) Attenuated rise in NYHA
functional class
Attenuated rise in NT-proBNP
Slower decline in eGFR
Lower loop diuretic requirement
Stable BP profile
Propensity score
matching 1:1 using
16 variables
Over 28 months, lower:
Untreated
Treated with propensity- + All-cause mortality
SGLT2i matched . Qu
(n= 220) Ces, + Composite CV mortality and HHF
Note: SGLT2i therapy was associated with a 4.5% discontinuation rate over 28 months.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
Conventional Heart Failure Medical Therapy in ATTR-CM
Benefits in
ATTR-CM
Well-tolerated; may
Potential/Unknown
Benefits in ATTR-CM
Challenges in
ATTR-CM
Fixed stroke volume;
Future
Considerations
MRAS reduce mortality with | Renal protective effect | fragile fluid homeostasis; | Acute HF hospitalisation
HEmrEF and HFpEF autonomic dysfunction
Well-tolerated; B
, a Reduction of HF
: improves volume status FE a , | Acute HF hospitalisation;
salrzı and decreases diuretic | hospitalisation and | Fragile fluid homeostasis renal biomarker
: mortality
resistance
www.peervoice.com/FMW870
Copyright © 2010-2025, PeerVoice
Conventional Heart Failure Medical Therapy in ATTR-CM
Benefits in
ATTR-CM
Well-tolerated; may
Potential/Unknown
Benefits in ATTR-CM
Challenges in
ATTR-CM
Fixed stroke volume;
Future
Considerations
MRAS reduce mortality with | Renal protective effect | fragile fluid homeostasis; | Acute HF hospitalisation
HEmrEF and HFpEF autonomic dysfunction
Well-tolerated; B
, a Reduction of HF
: improves volume status FE a , | Acute HF hospitalisation;
salrzı and decreases diuretic | hospitalisation and | Fragile fluid homeostasis renal biomarker
: mortality
resistance
www.peervoice.com/FMW870
Copyright © 2010-2025, PeerVoice
PeerVoice
Abbreviations and References
Combination Therapies in ATTR-CM
Abbreviation(s): ATTR-CM: transthyretin amyloid (ATTR) cardiomyopathy,
Reference(s): Gonzalez-Lopez E et al. Eur Heart J. 2025;46:999-1013.
HELIOS-B: Effect of Vutrisiran vs Placebo on CV Outcomes
Abbreviation(s): CV: cardiovascular; HF: heart failure; RR: relative risk.
Reference(s): Witteles RM et al. J Am Coll Cardiol. 2025:85:50735-1097(25)06170-4.
SGLT2i Use in ATTR-CM: Study Findings
Abbreviation(s): BP: blood pressure; eGFR: estimated glomerular filtration rate; HHF: hospitalisation for HF;
NT-proBNP: N-terminal pro-8-type natriuretic peptide; NYHA: New York Heart Association; SGLT2i: sodium-glucose
cotransporter-2 inhibitor.
Reference(s): Porcari A et al. J Am Coll Cardiol. 2024;83:241-2422.
Conventional Heart Failure Medical Therapy in ATTR-CM
Abbreviation(s): HFmrEF: HF with mid-range ejection fraction; HFpEF: HF with preserved ejection fraction;
MRA: mineralocorticoid receptor antagonist.
Reference(s): Schwarting SK et al. Circ Heart Fail. 2025;18:e011796.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
Abbreviations and References
Combination Therapies in ATTR-CM
Abbreviation(s): ATTR-CM: transthyretin amyloid (ATTR) cardiomyopathy,
Reference(s): Gonzalez-Lopez E et al. Eur Heart J. 2025;46:999-1013.
HELIOS-B: Effect of Vutrisiran vs Placebo on CV Outcomes
Abbreviation(s): CV: cardiovascular; HF: heart failure; RR: relative risk.
Reference(s): Witteles RM et al. J Am Coll Cardiol. 2025:85:50735-1097(25)06170-4.
SGLT2i Use in ATTR-CM: Study Findings
Abbreviation(s): BP: blood pressure; eGFR: estimated glomerular filtration rate; HHF: hospitalisation for HF;
NT-proBNP: N-terminal pro-8-type natriuretic peptide; NYHA: New York Heart Association; SGLT2i: sodium-glucose
cotransporter-2 inhibitor.
Reference(s): Porcari A et al. J Am Coll Cardiol. 2024;83:241-2422.
Conventional Heart Failure Medical Therapy in ATTR-CM
Abbreviation(s): HFmrEF: HF with mid-range ejection fraction; HFpEF: HF with preserved ejection fraction;
MRA: mineralocorticoid receptor antagonist.
Reference(s): Schwarting SK et al. Circ Heart Fail. 2025;18:e011796.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
Part 4 of 4: Determining When to Transition Our Treatment Approach for ATTR-CM:
How Will We Define Success and Progression?
Emer Joyce, MB BCh BAO, PhD Carsten Tschöpe, MD, PhD Peter van der Meer, MD, PhD
University College Dublin Deutsches Herzzentrum der Charite University Medical Center Groningen
Mater University Hospital Berlin, Germany Groningen, The Netherlands
Dublin, Ireland
Copyright © 2010-2025, PeerVoice
Part 4 of 4: Determining When to Transition Our Treatment Approach for ATTR-CM:
How Will We Define Success and Progression?
Emer Joyce, MB BCh BAO, PhD Carsten Tschöpe, MD, PhD Peter van der Meer, MD, PhD
University College Dublin Deutsches Herzzentrum der Charite University Medical Center Groningen
Mater University Hospital Berlin, Germany Groningen, The Netherlands
Dublin, Ireland
Copyright © 2010-2025, PeerVoice
PeerVoice
Emer Joyce, MB BCh BAO, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Honoraria from Alnylam Pharmaceuticals, Inc.
layer AG; and Pfizer Inc.
Carsten Tschöpe, MD, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Speaker fee from AstraZeneca; Bayer AG; and Novartis AG.
Peter van der Meer, MD, PhD, has no financial interests/relationships or affiliations in relation to this
activity.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
Emer Joyce, MB BCh BAO, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Honoraria from Alnylam Pharmaceuticals, Inc.
layer AG; and Pfizer Inc.
Carsten Tschöpe, MD, PhD, has a financial interest/relationship or affiliation in the form of:
Consultant for Bayer AG.
Speaker fee from AstraZeneca; Bayer AG; and Novartis AG.
Peter van der Meer, MD, PhD, has no financial interests/relationships or affiliations in relation to this
activity.
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
Abbreviations and References
Future Directions and Open Questions in ATTR-CM
Abbreviation(s): ATTR-CM: transthyretin (TTR) amyloid cardiomyopathy.
Reference(s): Gonzalez-Lopez E et al. Eur Heart J. 2025;46:999-1013.
PeerVoice Activity; Emer Joyce, MB BCh BAO, PhD; Carsten Tschópe, MD, PhD; Peter van der Meer, MD, PhD; September
2025,
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
Abbreviations and References
Future Directions and Open Questions in ATTR-CM
Abbreviation(s): ATTR-CM: transthyretin (TTR) amyloid cardiomyopathy.
Reference(s): Gonzalez-Lopez E et al. Eur Heart J. 2025;46:999-1013.
PeerVoice Activity; Emer Joyce, MB BCh BAO, PhD; Carsten Tschópe, MD, PhD; Peter van der Meer, MD, PhD; September
2025,
www.peervoice.com/FMW870 Copyright © 2010-2025, PeerVoice
PeerVoice
Future Directions and Open Questions in ATTR-CM
Initial therapy according When to switch from one
to patient profile therapy to another
Absence of head-to-head
clinical studies When to stop therapy
Unsolved issues
regarding ATTR-CM
specific therapies
REE Long-term safety of TTR
Role of combinations depletion
Treatment of EN
asymptomatic patients
Financial burden
Copyright © 2010-2025, PeerVoice
Future Directions and Open Questions in ATTR-CM
Initial therapy according When to switch from one
to patient profile therapy to another
Absence of head-to-head
clinical studies When to stop therapy
Unsolved issues
regarding ATTR-CM
specific therapies
REE Long-term safety of TTR
Role of combinations depletion
Treatment of EN
asymptomatic patients
Financial burden
Copyright © 2010-2025, PeerVoice
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