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Additional Endpoints

Improvement in autonomic symptoms and ability to perform everyday activities1

Autonomic symptoms: 1,2,a

  • COMPASS 31 is a 31-item questionnaire that evaluates autonomic function across 6 domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor (score range 0 to 100)2,3
  • Patients receiving ONPATTRO® (patisiran) experienced a significant benefit relative to placebo in reduction of autonomic symptoms

    —In ONPATTRO-treated patients, improvement compared to baseline was seen for the orthostatic intolerance and gastrointestinal domains, the 2 domains that contribute most to the overall COMPASS 31 score4

Change in COMPASS 31 score from baseline at 18 monthsb-d

ONPATTRO® (patisiran)-treated patients had a decrease in autonomic symptoms from baseline at 18 months

aCOMPASS 31 scores at baseline were 30.6 with ONPATTRO and 30.3 with placebo.1bONPATTRO-placebo treatment difference (LS mean): -7.53.5 c95% CI: -11.9, -3.2.5 dNumber of patients assessed at 18 months was 136 with ONPATTRO and 53 with placebo.1

CI=confidence interval; COMPASS 31=Composite Autonomic Symptom Score 31; LS=least squares.

Activities of daily living: 1,2,e

  • R-ODS is a 24-item scale that evaluates limitations on everyday activity (score range 0 to 48)
  • Patients receiving ONPATTRO saw a significant benefit relative to placebo in the ability to perform activities of daily living and everyday function

Change in R-ODS score from baseline at 18 monthsf-h

ONPATTRO® (patisiran)-treated patients experienced improvement in their ability to perform everyday activities compared to placebo from baseline at 18 months

eR-ODS scores at baseline were 29.7 with ONPATTRO and 29.8 with placebo.1fONPATTRO-placebo treatment difference (LS mean): 9.0.5 g95% CI: 7.0, 10.9.5 hNumber of patients assessed at 18 months was 138 with ONPATTRO and 54 with placebo.1

CI=confidence interval; R-ODS=Rasch-built Overall Disability Scale; LS=least squares.

ONPATTRO improved other key
measures of disease burden1,5,6

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Increased 

  • Gait speed measured by 10-meter walk test (10MWT)
  • Gait speed from baseline at 18 months improved in ONPATTRO-treated
    patients by 0.08 m/sec     compared to placebo-treated patients whose speed worsened by -0.24 m/sec (p<0.001)a,b
  • 53% of patients treated with ONPATTRO showed an improvement in gait speed (change >0) at 18 months, compared to 13% of patients treated with placebo
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Improved 

  • ONPATTRO-treated patients maintained a better nutritional status at 18 months compared to placebo-treated patients as demonstrated by a 3.7-unit decrease in modified body mass index (mBMI) vs a 119-unit decrease in the placebo group (p<0.001)c,d
  • Separation from placebo was seen in the ONPATTRO-treated patients as early as 3 months
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Improved 

  • ONPATTRO-treated patients experienced a 0.1-point increase from baseline at 18 months in Neuropathy Impairment Score-Weakness (NIS-W) compared with the placebo-treated patients whose score increased by 17.9 points (p<0.001)e,f
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Improved patient mobility, self-care, usual activities, pain/discomfort, and anxiety/depression7,8

  • ONPATTRO-treated patients showed improvement at 18 months in these domains of the Euro Quality of Life 5 Dimensions 5 Levels (EQ-5D-5L) instrument compared to placebo-treated patients
  • EQ-5D-5L was an exploratory endpoint in the APOLLO study

aONPATTRO-placebo treatment difference (LS mean): 0.31.6 b95% CI: 0.23, 0.39.6 cONPATTRO-placebo treatment difference (LS mean): 116.6 d95% CI: 82, 149.6 eONPATTRO-placebo treatment difference (LS mean): -17.9.5 f95% CI: -22.3, -13.4.5
CI=confidence interval; LS=least squares.

NEXT: Learn about
the safety profile of ONPATTRO
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References:

  1. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21.
  2. Adams D, Suhr OB, Dyck PJ, et al. BMC Neurol. 2017;17(1):181.
  3. Sletten DM, Suarez GA, Low PA, et al. Mayo Clin Proc. 2012;87(12):1196-1201.
  4. Data on File CSR. Alnylam Pharmaceuticals, Inc. 2018. 
  5. Center for Drug Evaluation and Research. NDA 210922—patisiran—cross-discipline team leader review. U.S. Department of Health and Human Services, Food and Drug Administration; 2018.
  6. ONPATTRO [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc; 2018.
  7. Adams D, Gonzalez-Duarte A, O’Riordan W, et al. Slides presented at: American Academy of Neurology; April 25, 2018; Los Angleles, CA.
  8. Herdman M, Gudex C, Lloyd A, et al. Qual Life Res. 2011;20(10):1727-1736.
  9. Berk K, Lin H, Agarwal S, et al. Poster presented at: XVIth International Symposium on Amyloidosis; March 26-29, 2018; Kumamoto, Japan.
  10. van Nes SI, Vanhoutte EK, van Doorn PA, et al. Neurology. 2011;76(4):337-345.
  11. Suhr O, Danielsson A, Holmgren G, et al. J Intern Med. 1994;235(5):479-485.