ATTR-CM-Study Design

HELIOS-B Clinical Trial

HELIOS-B was a landmark clinical trial establishing the efficacy and safety of AMVUTTRA® in ATTR-CM1

A global, randomized, double-blind, placebo-controlled, Phase 3 study1-3

Chart showing the HELIOS-B study designChart showing the HELIOS-B study design

  • Following the double-blind (DB) period of up to 36 months, patients on placebo were eligible to transition to AMVUTTRA in the open-label extension, which lasted up to 24 months2
  • Randomization was stratified according to tafamidis use at baseline (with vs without), ATTR disease type (hereditary vs wild-type), and NYHA class and age at baseline (NYHA class I or II and age <75 years vs all others)1

*The overall population included patient cohorts with and without tafamidis use at baseline.1

†Cardiovascular events are defined as hospitalizations for cardiovascular causes or urgent visits for heart failure.1

6-MWT=6-minute walk test; ATTR=transthyretin-mediated amyloidosis; ATTR-CM=cardiomyopathy of transthyretin-mediated amyloidosis; hATTR=hereditary ATTR; mg=milligram; KCCQ‑OS=Kansas City Cardiomyopathy Questionnaire-Overall Summary; NT-proBNP=N-terminal prohormone of brain‑type natriuretic peptide; NYHA=New York Heart Association; q3m=every 3 months; SC=subcutaneous; wtATTR=wild-type ATTR.

One of the largest studies with a contemporary population of patients with ATTR-CM2,4,5*

HELIOS-B enrolled a population representative of present-day patients with ATTR-CM, characterized by2,3:

  • Earlier diagnoses
  • Less severe disease
  • Increased heart-failure management
~80% were on diuretics at baseline
~30% started SGLT2 inhibitors during the double-blind period
  • Concomitant ATTR-CM medication
~40% were on tafamidis at baseline
AMVUTTRA achieved statistically significant results across all study endpoints despite increased disease management of patients with ATTR-CM.1‑3
*Compared to other interventional pivotal studies for ATTR-CM.2,4,5
  • Use of background HF medications and concomitant ATTR-CM therapy was similar across the AMVUTTRA and placebo study arms2
  • SGLT2 inhibitors were added to HF guidelines in 2022, reinforcing their role as a standard of care in treatment of patients with HF6

The monotherapy population comprised ~60% of patients in HELIOS-B1,2

The monotherapy population only included those not receiving tafamidis at baseline. Patients in the monotherapy population were permitted to initiate tafamidis during the DB period. The median time to initiation of tafamidis was ~18 months across both arms.

AMVUTTRA Monotherapy (n=196)3

Pie chart showing 78% of patients received AMVUTTRA alone and 22% initiated tafamidis during the DB periodPie chart showing 78% of patients received AMVUTTRA alone and 22% initiated tafamidis during the DB period

Placebo Monotherapy (n=199)3

Pie chart showing 79% of patients received placebo alone and 21% initiated tafamidis during the DB periodPie chart showing 79% of patients received placebo alone and 21% initiated tafamidis during the DB period
The monotherapy population may be representative of patients receiving first-line therapy

The study population was typical of present-day patients with ATTR-CM2

Patient Characteristics at Baseline
Table showing the HELIOS-B baseline characteristics for overallTable showing the HELIOS-B baseline characteristics for overall
 

 

Table showing the HELIOS-B baseline characteristics for overall

HF=heart failure; IQR=interquartile range; NT-proBNP=N-terminal prohormone of brain-type natriuretic peptide; SD=standard deviation; SLGT2=sodium-glucose cotransporter-2.
Patients treated with AMVUTTRA had higher NT‑proBNP and troponin I levels at baseline compared with placebo.2,3

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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. Fontana et al. N Engl J Med. 2025;392(1):33-44.
  3. Fontana et al. N Engl J Med. 2025;392(1):33-44 (supplement).
  4. Gillmore et al. N Engl J Med. 2024;390(2):132-142.
  5. Tomasoni et al. Front Cardiovasc Med. 2023;10:1154594.
  6. Heidenreich et al. Circulation. 2022;145(18):e895-e1032.