Efficacy

AMVUTTRA® significantly improved polyneuropathy1,2

Primary endpoint: change from baseline at 9 months in mNIS+71

 

  • mNIS+7 is a composite measure that assessed motor strength, reflexes, sensation, nerve conduction, and postural blood pressure (score range 0 to 304), with higher scores representing a greater severity of disease1
mNIS+7=modified Neuropathy Impairment Score + 7.
Change from baseline in mNIS+71,2,a-c
About mNIS+7 assessment1,3
 

Change in mNIS+7 from baseline at 18 months with AMVUTTRA® (vutrisiran) versus external placebo

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

bBars represent SEM.

cN=number of evaluable patients.

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

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

 

Change from baseline in mNIS+71,2,a-c
Change in mNIS+7 from baseline at 18 months with AMVUTTRA® (vutrisiran) versus external placebo

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

bBars represent SEM.

cN=number of evaluable patients.

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

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

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

bBars represent SEM.

cN=number of evaluable patients.

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

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

 

Modified Neuropathy Impairment Score + 7 (mNIS+7) components

Modified Neuropathy Impairment Score + 7 (mNIS+7)1,3

  • 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 mNIS+7 assessment1,3
Modified Neuropathy Impairment Score + 7 (mNIS+7) components

Modified Neuropathy Impairment Score + 7 (mNIS+7)1,3

  • 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

48% of patients treated with AMVUTTRA experienced reversal in neuropathy impairment from baseline2,a-c

Reversal in neuropathy impairment from baseline at 18 monthsa-c

mNIS+7 Reversal in Neuropathy Impairment from Baseline at 18 months graph

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

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

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

d95% CI: 39.3, 57.3.2

e95% CI: 0.0, 8.2.2

mITT=modified intention-to-treat.

Reversal in neuropathy impairment from baseline at 18 monthsa-c
mNIS+7 Reversal in Neuropathy Impairment from Baseline at 18 months graph

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

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

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

d95% CI: 39.3, 57.3.2

e95% 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)4

AMVUTTRA demonstrated consistent neurologic benefits across all subgroups, including age, sex, V30M variant status, previous TTR stabilizer use, and disease stage.1,2

AMVUTTRA significantly improved quality of life2

AMVUTTRA helped to alleviate the burden of the disease, as measured by Norfolk QoL-DN1,2

 

  • 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 (score range -4 to 136), with higher scores representing greater impairment1
Norfolk QoL-DN=Norfolk Quality of Life-Diabetic Neuropathy.
Change from baseline in Norfolk QoL-DN score2,a-c
About Norfolk QoL-DN assessment5-7
 

Change in Norfolk QoL-DN from baseline at 18 months with AMVUTTRA® (vutrisiran) versus external placebo

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

bBars represent SEM.

cN=number of evaluable patients.

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

 

Change from baseline in Norfolk QoL-DN score2,a-c
Change in Norfolk QoL-DN from baseline at 18 months with AMVUTTRA® (vutrisiran) versus external placebo

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

bBars represent SEM.

cN=number of evaluable patients.

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

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

bBars represent SEM.

cN=number of evaluable patients.

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

Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN)5-7

  • 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
  • Score ranges from -4 to 136; higher score indicates worsening quality of life

 

Sample questions7:

  • Have you felt unsteady on your feet?
  • Have you had a problem walking down stairs?
  • Have you had a problem with bathing or showering?
  • Have you had a problem with dressing?
  • Were you limited in the kind of work or other activities you could perform?

57% of patients treated with AMVUTTRA experienced improvement in quality of life from baseline at 18 months, compared with 10% of patients in the external placebo group.2

AMVUTTRA improved nutritional status2

Only AMVUTTRA has been able to show an improvement from baseline in mBMI after 1 dose.1,8-10

  • Patients treated with AMVUTTRA experienced significant improvement in nutritional status from baseline at 18 months compared with placebo-treated patients, who experienced a decline (25.0 units, -115.7 units, respectively [p<0.001])2
mBMI=modified Body Mass Index.
Change from baseline in mBMI10,a-c

Graph about AMVUTTRA® (vutrisiran) and impact on nutritional status.

aMean mBMI baseline was 1057.4 with AMVUTTRA and 989.9 with external placebo group.10

bBars represent SEM.

cN=number of evaluable patients.

dLS mean difference 140.7 (95% CI: 108.4, 172.9).10

Change from baseline in mBMI10,a-c
Graph about AMVUTTRA® (vutrisiran) and impact on nutritional status.

aMean mBMI baseline was 1057.4 with AMVUTTRA and 989.9 with external placebo group.10

bBars represent SEM.

cN=number of evaluable patients.

dLS mean difference 140.7 (95% CI: 108.4, 172.9).10

56% of patients treated with AMVUTTRA experienced an improvement in mBMI from baseline at 18 months, compared with 7% of patients in the external placebo group.4

About mBMI assessment1,11:

  • 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
AMVUTTRA improved other key measures of disease burden
Sneaker icon
  • Patients treated with AMVUTTRA maintained a better gait speed from baseline at 18 months compared with those treated with placebo (-0.024 m/sec, -0.264 m/sec, respectively [p<0.001])2

About 10MWT assessment1:

  • Measure of gait speed (m/sec)
  • A higher number indicates less disability/less impairment
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  • Patients treated with AMVUTTRA were better able to perform activities of daily living compared with placebo-treated patients (LS mean change from baseline at 18 months was -1.5 and -9.9, respectively [p<0.001])2

R-ODS3,12:

  • 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
Sample questions icon

Sample questions12:

Are you able to:

  • Walk 1 flight of stairs?
  • Bend and pick up an object?
  • Take a shower?
  • Do the shopping?

A US expert panel recommended AMVUTTRA as one of the first-line treatments for the polyneuropathy of hATTR amyloidosis.13

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Up next Learn about the safety profile of AMVUTTRA

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 D, Tournev IL, Taylor MS, et al. Amyloid. 2023;30(1):18-26.
  3. Adams D, Suhr OB, Dyck PJ, et al. BMC Neurol. 2017;17(1):181.
  4. Data on file. Alnylam Pharmaceuticals, Inc.
  5. Vinik EJ, Hayes R, Oglesby A, et al. Diabetes Technol Ther. 2005;7(3):497-508.
  6. Vinik EJ, Vinik AI, Paulson JF, et al. J Peripher Nerv Syst. 2014;19(2):104-114.
  7. Vinik EJ, Vinik AI. In: Farquhar I, Summers KH, Sorkin A, eds. The Value of Innovation: Impact on Health, Life Quality, Safety, and Regulatory Research. Bingley, UK: Emerald Group Publishing Ltd; 2007;16:29-52.
  8. ONPATTRO Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.
  9. WAINUA Prescribing Information. Wilmington, DE: AstraZeneca Pharmaceuticals LP.
  10. Obici L, Ajroud-Driss S, Lin KP, et al. Neurol Ther. 2023;12(1):1759-1775.
  11. Suhr OB, Danielsson A, Holmgren G, et al. J Intern Med. 1994;235(5):479-485.
  12. van Nes SI, Vanhoutte EK, van Doorn PA, et al. Neurology. 2011;76(4):337-345.
  13. Karam C, Mauermann ML, Gonzalez-Duarte A, et al. Muscle Nerve. 2024;69(3):273-287.