Efficacy

AMVUTTRA® significantly improved polyneuropathy1,2

Primary endpoint: change from baseline at 9 months in mNIS+71,2

 

Choose below to see:

Change from baseline in mNIS+71,2,a-c
About mNIS+7 assessment
 
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 (standard error of the mean).

cN=number of evaluable patients.

CI=confidence interval; LS=least squares.

 
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 (standard error of the mean).

cN=number of evaluable patients.

CI=confidence interval; LS=least squares.

 
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 assessment
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

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

aOdds ratio: 22.9 (6.8, 76.9). 

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

c95% CI: 39.3, 57.3.

d95% CI: 0.0, 8.2.

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

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

aOdds ratio: 22.9 (6.8, 76.9). 

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

c95% CI: 39.3, 57.3.

d95% CI: 0.0, 8.2.

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

  • For the 55 evaluable AMVUTTRA-treated patients 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

mITT=modified intention-to-treat; mNIS+7=modified Neuropathy Impairment Score + 7; Norfolk QoL-DN=Norfolk Quality of Life-Diabetic Neuropathy; TTR=transthyretin.

AMVUTTRA significantly improved quality of life2

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

 

Choose below to see:

Change from baseline in Norfolk QoL-DN score2,a-c
About Norfolk QoL-DN assessment
 
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.

 
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.

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.

Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN)1,5,6

  • 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, with higher scores representing greater impairment

 

Sample questions5:

  • 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 other key measures of disease burden

key measures of disease burden

Fork, plate, and knife icon
  • AMVUTTRA-treated patients 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
    • Improvement in mBMI vs placebo was observed after 1 dose of AMVUTTRA7

About mBMI assessment1,8:

  • 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
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  • 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 assessment1,9:

  • Measure of gait speed (m/sec)
  • A higher number indicates less disability/less impairment 
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  • AMVUTTRA-treated patients 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

About R-ODS assessment4,10,11:

  • 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 questions10,11:

Are you able to:

  • Walk 1 flight of stairs?
  • Carry and put down a heavy object? 
  • Take a shower?
  • Do the shopping?
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Up next Learn about the safety profile of AMVUTTRA

Important Safety Information and Indication

Important Safety Information

Reduced Serum Vitamin A Levels and Recommended Supplementation

AMVUTTRA® (vutrisiran) 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

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%).

Indication

AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis 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. 2022. Published online July 23, 2022. doi.org/10.1080/13506129.2022.2091985.
  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, 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.
  6. Vinik EJ, Vinik AI, Paulson JF, et al. J Peripher Nerv Syst. 2014;19(2):104-114.
  7. Ajroud-Driss S, Berk JL, Adams D, et al. Slides presented at: Peripheral Nerve Society (PNS) Annual Meeting; May 14-17, 2022.
  8. Suhr O, Danielsson A, Holmgren G, et al. J Intern Med. 1994;235(5):479-485.
  9. Adams D, González-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21.
  10. Van Nes SI, Vanhoutte EK, Van Doorn PA, et al. Neurology. 2011;76(4):337-345.
  11. Berk J, Lin H, Agarwal S, et al. Poster presented at XVIth International Symposium on Amyloidosis; March 26-29, 2018; Kumamoto, Japan.