hATTR-PN Efficacy

HELIOS-A Efficacy

Primary endpoint: Change from baseline at 9 months in mNIS+71,2*†‡

Chart showing the change from baseline mNIS+7Chart showing the change from baseline mNIS+7

 
Primary endpoint: Change from baseline at 9 months in mNIS+71,2*†‡

Chart showing the change from baseline mNIS+7

mNIS+7 is a composite measure that assesses motor strength, reflexes, sensation, nerve conduction, and postural blood pressure (score range 0 to 304), with higher scores representing a greater severity of disease.1

*Mean mNIS+7 at baseline was 60.6 with AMVUTTRA and 74.6 with external placebo group.1,2

†Bars represent SEM.

‡N=number of evaluable patients.

§LS mean difference -28.6 (95% CI: -34.0, -23.1).2

CI=confidence interval; LS=least squares; SEM=standard error of the mean.

AMVUTTRA® significantly improved polyneuropathy1,2

48% of patients treated with AMVUTTRA experienced reversal in neuropathy impairment from baseline2*†‡

Exploratory Analysis

Reversal in neuropathy impairment from baseline at 18 months2*†‡

Chart showing reversal in neuropathy impairment from baseline at 18 monthsChart showing reversal in neuropathy impairment from baseline at 18 months

*Odds ratio: 22.9 (6.8, 76.9); nominal p-value.2

†Percentages based on mITT population: AMVUTTRA (n=118); external placebo group (n=77).2

‡Reversal defined as mNIS+7 change from baseline of <0 points.2

§95% CI: 39.3, 57.3.2

95% CI: 0.0, 8.2.2

mITT=modified intention-to-treat.

For the 55 evaluable patients treated with AMVUTTRA who did not experience reversal in neuropathy impairment at 18 months, progression was slowed compared with the external placebo group (mean change of 11 points vs 30 points).3
AMVUTTRA demonstrated consistent results across all subgroups, including age, sex, V30M variant status, previous TTR stabilizer use, and disease stage.1,3

AMVUTTRA significantly improved quality of life1,2

Change from baseline in Norfolk QoL-DN score2*†‡

Chart showing change from baseline in Norfolk QoL-DN scoreChart showing change from baseline in Norfolk QoL-DN score

57% of patients treated with AMVUTTRA experienced improvement in quality of life from baseline compared with 10% of patients in the external placebo group, based on an exploratory analysis conducted at 18 months2
 

Change from baseline in Norfolk QoL-DN score2*†‡

Chart showing change from baseline in Norfolk QoL-DN score

Norfolk QoL-DN is a patient-reported assessment that evaluates the effects of neuropathy in domains such as physical functioning, activities of daily living, symptoms, and autonomic function (total score range -4 to 136), with higher scores representing greater impairment.1

*Norfolk QoL-DN scores at baseline were 47.1 with AMVUTTRA and 55.5 with external placebo group.1,2

†Bars represent SEM.

‡N=number of evaluable patients.

§LS mean difference -21.0 (95% CI: -27.1, -14.9).2

AMVUTTRA improved nutritional status2

Change from baseline in mBMI2,6*†‡
Chart showing change from baseline in mBMIChart showing change from baseline in mBMI
56% of patients treated with AMVUTTRA experienced an improvement in mBMI from baseline compared with 7% of patients in the external placebo group, based on an exploratory analysis conducted at 18 months3
 

Change from baseline in mBMI2,6*†‡

Chart showing change from baseline in mBMI

*Mean mBMI at baseline was 1057.4 with AMVUTTRA and 989.9 with external placebo group.6

†Bars represent SEM.

‡N=number of evaluable patients.

§LS mean difference 140.7 (95% Cl: 108.4, 172.9).6

Only AMVUTTRA has been able to show an improvement from baseline in mBMI after 1 dose.1,2,4-6

AMVUTTRA improved other key measures of disease burden

Gait speed: 10-meter walk test (10-MWT)
Patients treated with AMVUTTRA maintained a better gait speed from baseline at 18 months compared with those in the external placebo group (-0.024 m/sec, -0.264 m/sec, respectively [p<0.001]).2
Ability to perform everyday activities: Rasch-built Overall Disability Scale (R‑ODS) 
Patients treated with AMVUTTRA were better able to perform activities of daily living compared with the external placebo group (LS mean change from baseline at 18 months was -1.5 and -9.9, respectively [p<0.001]).2
A US expert panel recommended AMVUTTRA as one of the first-line treatments for the polyneuropathy of hATTR amyloidosis.7

Primary endpoint: About mNIS+7 assessment1,8
Chart about mNIS+7 assessmentChart about mNIS+7 assessment
  • Validated composite measure of motor, sensory, and autonomic neuropathy, with a score ranging from 0 (no impairment) to 304 points, with higher scores representing a greater severity of disease
About Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL‑DN)9-11
Patient questionnaire designed to capture the impact on a patient’s quality of life related to:
  • Activities of daily living
  • Polyneuropathy symptoms
  • Autonomic function
  • Small fiber nerve function
  • Physical functioning/large fiber nerve function
About mBMI assessment1,12:
  • Nutritional status assessment based on body mass index and serum albumin (kg/m2 x albumin [g/L])
  • Higher score indicates better nutritional status
  • mBMI is used as a tool to monitor disease progression and provide prognostic information, showing close correlation with duration of gastrointestinal disturbances, malabsorption, and functional capacity
About 10-MWT assessment1,2
  • Measure of gait speed (m/sec)
  • A higher number indicates less disability/less impairment
About R-ODS8,13
  • 24-item scale that evaluated patient-reported ability to perform activities of daily living such as eating, bathing, dressing, and standing
  • Score ranges from 0 to 48; higher score indicates less disability

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mNIS+7=modified Neuropathy Impairment Score + 7.
Norfolk QoL-DN=Norfolk Quality of Life-Diabetic Neuropathy.
mBMI=modified Body Mass Index.
 
 

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. Adams et al. Amyloid. 2023;30(1):18-26.
  3. Data on file. Alnylam Pharmaceuticals, Inc.
  4. ONPATTRO Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.
  5. WAINUA Prescribing Information. Wilmington, DE: AstraZeneca Pharmaceuticals LP.
  6. Obici et al. Neurol Ther. 2023;12(5):1759-1775.
  7. Karam et al. Muscle Nerve. 2024;69:273-287.
  8. Adams et al. BMC Neurol. 2017;17(1):181.
  9. Vinik et al. Diabetes Technol Ther. 2005;7(3):497-508.
  10. Vinik et al. J Peripher Nerv Syst. 2014;19(2):104-114.
  11. Vinik et al. The Value of Innovation: Impact on Health, Life Quality, Safety, and Regulatory Research. 
    Bingley, UK: Emerald Group Publishing Ltd; 2007;16:29-52.
  12. Suhr et al. J Intern Med. 1994;235(5):479-485.
  13. van Nes et al. Neurology. 2011;76(4):337-345.