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ONPATTRO® (patisiran) significantly improved polyneuropathy1

Primary Endpoint: 1,2

  • Change from baseline at 18 months vs placebo in modified Neuropathy Impairment Score + 7 (mNIS+7)
  • mNIS+7 is an objective 304-point assessment of polyneuropathy in hereditary transthyretin-mediated (hATTR) amyloidosis

Change in mNIS+7 score1,a-c

ONPATTRO® (patisiran) demonstrated significant improvement in polyneuropathy at 18 months from baseline versus placebo

 

  • The progression of polyneuropathy in the placebo arm was consistent with the natural progression of the disease described in previous studies3-5
  • Maintenance of efficacy as measured by mNIS+7 was demonstrated for up to 36 months in 2 OLE studies6

aMean mNIS+7 at baseline was 80.9 with ONPATTRO and 74.6 with placebo.1 bBars represent SEM. cN=number of evaluable patients. d95% CI: -20.7, -11.3.1 e95% CI: -39.9, -28.1.1

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

ONPATTRO demonstrated significant improvement vs placebo across the sensory, motor, and autonomic components associated with mNIS+7.1

Reversal in neuropathy
impairment
from baseline at 18 months3,f,g

Percentage of patients in APOLLO who experienced reversal in neuropathy impairment from baseline at 18 months

From New England Journal of Medicine, Adams D, Gonzalez-Duarte A, O’Riordan WD, et al, "Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis," 379(1). Copyright © 2018 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.

fOdds ratio: 39.9 (11.0-144.4).3 gPercentages based on mITT population: ONPATTRO(n=148); placebo (n=77).1 h95% CI: 48, 64.3 i95% CI: 0,8.3 jReversal defined as mNIS+7 change from baseline of <0 points.

mITT=modified Intention-To-Treat.

More than half of patients treated with ONPATTRO experienced reversal in neuropathy impairment from baseline3

  • At 18 months, 56% of ONPATTRO-treated patients experienced reversal in neuropathy impairment compared to 4% of placebo-treated patients3
  • For the 54 ONPATTRO-treated patients who did not experience reversal in neuropathy impairment, progression was slowed compared to the placebo arm (median change of 10 points vs 26 points)3
 

The benefit of ONPATTRO on neuropathy impairment was observed across all subgroups, including age, sex, V30M mutation status, previous tetramer stabilizer use, and disease stage.1,3

Earlier treatment with ONPATTRO substantially reduced polyneuropathy impairment

Following progression of polyneuropathy over 18 months, patients who received placebo in the APOLLO study and entered into the OLE study experienced a mean reduction in mNIS+7 after 12 months of treatment with ONPATTRO.6

Change in mNIS+7 from baseline in APOLLO and global OLEk-m

In an open-label extension study, results showed that earlier treatment with ONPATTRO® (patisiran) substantially reduced polyneuropathy impairment

kFor APOLLO patients initiating alternative hATTR amyloidosis treatment, mNIS+7 assessments after alternative treatment are missing. lBars represent SEM (standard error of the mean). mN=number of evaluable patients.

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References:

  1. ONPATTRO [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc.; 2018.
  2. Adams D, Suhr OB, Dyck PJ, et al. BMC Neurol. 2017;17(1):181.
  3. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21.
  4. Koike H, Tanaka F, Hashimoto R, et al. Neurol Neurosurg Psychiatry. 2012;83:152-158.
  5. Berk J, Suhr O, Obici L, et al. JAMA. 2013;310(24):2658-2667.
  6. Gonzalez-Duarte A, Coelho T, Adams D, et al. Poster presented at: AANEM Annual Meeting; October 10-13, 2018; Washington, DC.