ATTR-CM Efficacy

HELIOS-B Efficacy

AMVUTTRA® significantly reduced the risk of ACM and recurrent CV events1

Primary composite endpoint analysis through 33-36 months1 

OVERALL POPULATION

Relative risk reduction 
of ACM and recurrent CV events

(N=654)

[HR=0.72 (95% CI: 0.55–0.93); p=0.01]

MONOTHERAPY POPULATION

Relative risk reduction 
of ACM and recurrent CV events

(N=395)

[HR=0.67 (95% CI: 0.49–0.93); p=0.02]

4 patients in the overall population and 3 patients in the monotherapy population need to be treated to prevent 1 death or CV event in the DB period2*

Components of the Composite1,2
Chart showing components of the compositeChart showing components of the composite
ACM=all-cause mortality; CI=confidence interval; CV=cardiovascular; HR=hazard ratio.
The majority of deaths were CV-related (77%).1
Analysis for components of the composite not adjusted for multiplicity.3

*During the 33-36 month DB period, NNT=3.4 in the overall population and 2.7 in the monotherapy population. ARR (per 100 patient-years) was 9.9 in the overall population and 12.5 in the monotherapy population.2

ARR=absolute risk reduction; DB=double-blind; NNT=number needed to treat.

AMVUTTRA significantly reduced the risk of ACM and recurrent CV events1-3

Time to First CV Event or All-Cause Mortality (Overall Population)1*†‡

Chart showing time to first CV event or all-cause mortality (overall population)Chart showing time to first CV event or all-cause mortality (overall population)
 

Time to First CV Event or All-Cause Mortality (Overall Population)1*†‡

Chart showing time to first CV event or all-cause mortality (overall population)

*The Kaplan-Meier curves are unadjusted for baseline imbalances in disease-severity characteristics.3

†Heart transplantation and left ventricular assist device placement are treated as death. HR and 95% CI are based on a Cox proportional-hazards model.1

‡Data were censored at each patient's first dose in the OLE, which could occur at approximately 33 or 36 months, depending on the patient's enrollment time. For patients who did not enter the OLE, data were censored at their study discontinuation date.3

CI=confidence interval; CV=cardiovascular; DB=double-blind; HR=hazard ratio; OLE=open-label extension.

AMVUTTRA achieved consistent results across all prespecified subgroups1

Subgroup Analyses of the Composite of ACM and Recurrent CV Events (Overall Population)1*
Subgroup analyses of the primary endpointSubgroup analyses of the primary endpoint
Subgroup analyses may be limited by small patient numbers and are not powered to detect statistical significance.
*HR and 95% CI are based on modified Andersen-Gill model analyses.1
ATTR=transthyretin-mediated amyloidosis; CI=confidence interval; HR=hazard ratio; NT-proBNP=N-terminal prohormone of brain‑type natriuretic peptide; NYHA=New York Heart Association.
AMVUTTRA significantly reduced the risk of ACM3
A key secondary endpoint was all-cause mortality through 42 months, which included up to 36 months of the double-blind (DB) period plus 6 months of the open-label extension.3

At the end of the DB period, all remaining patients on placebo transitioned to AMVUTTRA treatment in the OLE.3 

An updated analysis was conducted to incorporate additional patient follow-up data, which was not controlled for multiplicity.4§

All-Cause Mortality (Overall Population)2,4,5*†‡

Chart showing all-cause mortality (overall population)Chart showing all-cause mortality (overall population)
 

All-Cause Mortality (Overall Population)2,4,5*†‡

Chart showing all-cause mortality (overall population)

Figure depicts results of updated analysis.

*The Kaplan-Meier curves are unadjusted for baseline imbalances in disease-severity characteristics.3

†Heart transplantation and left ventricular assist device placement are treated as death.6

‡For patients in both treatment arms, survival time was censored 6 months after the first dose in the OLE period.3

§Initial analysis (May 2024 data cut): 42.4% of patients with data through 42 months. Updated analysis (Nov 2024 data cut): 96.3% of patients with data through 42 months.4

CI=confidence interval; HR=hazard ratio.

Significant benefit observed in functional capacity and quality of life for patients treated with AMVUTTRA compared with placebo1,6

Secondary Endpoints: 6-MWT and KCCQ-OS Change From Baseline at 30 Months1,2*†
Chart showing secondary endpoints: 6-MWT and KCCQ-OS change from baseline at 30 months (overall population)Chart showing secondary endpoints: 6-MWT and KCCQ-OS change from baseline at 30 months (overall population)
 

Secondary Endpoints: 6-MWT and KCCQ-OS Change From Baseline at 30 Months (Overall Population)1,2*✝

Chart showing secondary endpoints: 6-MWT and KCCQ-OS change from baseline at 30 months (overall population)

Analyses include estimates for missing data (imputed data) to account for death or inability to walk (for 6-MWT only).2

*6-MWT assesses functional capacity by measuring distance walked over a period of 6 minutes. A decrease in the distance walked indicates a decline in functional capacity.9

†The KCCQ is a 23-item, self-administered questionnaire that measures the patient’s perception of health status within a 2-week recall period (scoring on KCCQ-OS: 0 to 100, with a higher score indicating better quality of life).3

6-MWT=6-minute walk test; CI=confidence interval; KCCQ-OS=Kansas City Cardiomyopathy Questionnaire-Overall Summary; LS=least squares; SE=standard error.

 

  • Healthy adults without ATTR-CM experience a natural decline in 6‑MWT of 5‑6 meters per year7
  • A 5-point change in KCCQ‑OS (a measure of health status and health‑related QoL) is considered clinically meaningful8

*6-MWT assesses functional capacity by measuring distance walked over a period of 6 minutes. A decrease in the distance walked indicates a decline in functional capacity.9

†The KCCQ is a 23-item, self-administered questionnaire that measures the patient’s perception of health status within a 2-week recall period (scoring on KCCQ-OS: 0 to 100, with a higher score indicating better quality of life).3

6-MWT=6-minute walk test; CI=confidence interval; KCCQ-OS=Kansas City Cardiomyopathy Questionnaire-Overall Summary; LS=least squares; SE=standard error.

 

Patients receiving AMVUTTRA maintained relative stability in functional capacity and quality of life3

Median changes reflect observed data that were directly measured, not estimated. Statistical testing was not conducted.3
Observed 6-MWT (Overall Population)3,5
Chart showing observed 6-MWT (overall population)Chart showing observed 6-MWT (overall population)
 

Observed 6-MWT (Overall Population)3,5

Chart showing observed 6-MWT (Overall Population)

Observed  KCCQ-OS Score (Overall Population)3,5
Chart showing observed KCCQ-OS score (overall population)Chart showing observed KCCQ-OS score (overall population)
 

Observed KCCQ-OS Score (Overall Population)3,5

Chart showing observed KCCQ-OS score (overall population)

Patients treated with AMVUTTRA maintained relative stability in their functional capacity and health-related QoL at 30 months compared to their pre-treatment baselines.3

QoL=quality of life.

Biomarkers associated with heart failure favored AMVUTTRA over placebo1

Exploratory Analyses
Chart showing NT-proBNP change over time (overall population)Chart showing NT-proBNP change over time (overall population)
 

NT-proBNP Change Over Time (Overall Popupation)3,5

Chart showing NT-proBNP change over time (overall population)

  • Analyses were exploratory and not adjusted for multiplicity.3
 

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CV=cardiovascular. 
NYHA=New York Heart Association. 
NT-proBNP=N-terminal prohormone of brain natriuretic peptide. 
6-MWT=6-minute walk test. 
KCCQ-OS=Kansas City Cardiomyopathy Questionnaire Overall Summary. 
ACM=all-cause mortality. 
CV=cardiovascular. 
 
 

Important Safety Information

Reduced Serum Vitamin A Levels and Recommended Supplementation

AMVUTTRA treatment leads to a decrease in serum vitamin A levels.

Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).

Adverse Reactions

In a study of patients with hATTR-PN, the most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).

In a study of patients with ATTR-CM, no new safety issues were identified.

For additional information about AMVUTTRA, please see the full Prescribing Information.

Indications

AMVUTTRA® (vutrisiran) is indicated for the treatment of the:

  • cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits.
  • polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.

For additional information about AMVUTTRA, please see the full Prescribing Information.

References

  1. AMVUTTRA Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.
  2. Data on file. Alnylam Pharmaceuticals, Inc.
  3. Fontana et al. N Engl J Med. 2025;392(1):33-44 (supplement).
  4. Witteles et al. J Am Coll Cardiol. 2025;85(20):1959-1970.
  5. Fontana et al. ESC Congress 2024. London, UK.
  6. Fontana et al. N Engl J Med. 2025;392(1):33-44.
  7. Enright and Sherrill. Am J Respir Crit Care Med. 1998;158(5 Pt 1):1384-1387.
  8. Spertus et al. J Am Coll Cardiol. 2020;76(20):2379-2390.
  9. Fell et al. Heart Lung. 2022;52:117-122.
  10. Maurer et al. HFSA Annual Scientific Meeting 2024.