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Impact of patisiran on norfolk QOL-DN in patients with hereditary transthyretin-mediated amyloidosis: results from the cardiac subpopulation in the phase 3 apollo study

Session Patient management - From oral treatment to transplant

Speaker Verena Karsten

Congress : Heart Failure 2018

  • Topic : heart failure
  • Sub-topic : Chronic Heart Failure: Pharmacotherapy
  • Session type : Rapid Fire Abstracts
  • FP Number : 1546

Authors : G Merlini (Pavia,IT), S Solomon (Boston,US), D Adams (Le Kremlin-Bicêtre,FR), T Coelho (Porto,PT), T Damy (Paris,FR), M Mauer (New York,US), AM Partisano (Cambridge,US), J Chen (Cambridge,US), V Karsten (Cambridge,US), J Vest (Cambridge,US), OLE Suhr (Umea,SE), A Kristen (Heidleberg,DE)


G Merlini1 , S Solomon2 , D Adams3 , T Coelho4 , T Damy5 , M Mauer6 , AM Partisano7 , J Chen7 , V Karsten7 , J Vest7 , OLE Suhr8 , A Kristen9 , 1IRCCS Policolinico San Matteo - Pavia - Italy , 2Brigham and Women' s - Boston - United States of America , 3National Reference Center for FAP (NNERF)/ APHP/ INSERM U 1195/ CHU Bicêtre - Le Kremlin-Bicêtre - France , 4Hosptial de Santo Antonio - Porto - Portugal , 5Universite Paris-Est Creteil Val De Marne - Paris - France , 6HCM Center at New York-Presbyterian Hospital/Columbia University Medical Center - New York - United States of America , 7Alnylam Pharmaceuticals - Cambridge - United States of America , 8Umea University Hospital - Umea - Sweden , 9Heidelberg University Hospital - Heidleberg - Germany ,


Background/Introduction: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, multi-systemic, progressive, fatal disease. Heterogeneous clinical presentation of hATTR amyloidosis includes sensory, motor and autonomic neuropathy, gastrointestinal symptoms and cardiac involvement resulting in substantial disease burden for patients impacting their quality of life (QOL). Patisiran, an investigational RNAi therapeutic, was evaluated in hATTR patients with polyneuropathy in the APOLLO study and resulted in a statistically significant improvement in the neuropathy (measured by modified neuropathy impairment, mNIS+7) and QOL (measured by Norfolk QOL-DN) scores compared to placebo and was generally well tolerated. To investigate cardiac involvement, APOLLO included a pre-defined cardiac subpopulation.

Purpose:  Evaluate the impact of patisiran compared to placebo on Norfolk QOL-DN scores in the pre-defined cardiac subpopulation enrolled in the APOLLO trial.

Methods: APOLLO was a Phase 3 multi-center, international, randomized (2:1), double-blind, study of patisiran 0.3mg/kg or placebo IV q3W in patients with hATTR amyloidosis (NCT01960348). Pre-defined cardiac subpopulation included patients with baseline left ventricular (LV) wall thickness = 13mm and no medical history of aortic valve disease or hypertension. Norfolk QOL-DN, a secondary endpoint of the trial, assessed 5 domains: small fiber neuropathy, physical functioning/large fiber; autonomic neuropathy; activities of daily living; and symptoms. Scores for this QOL instrument range from -4 to 136 with a lower score indicating QOL improvement.

Results: APOLLO enrolled 225 patients, the cardiac subpopulation comprised 56% of the total population and had a mean age 61 years (54-67); 78% males; 27% V30M. Mean (95% CI) baseline Norfolk QOL-DN values for patisiran (n=90) and placebo (n=35) in the cardiac subpopulation were 61 (17,102) and 64 (5,119), respectively.  In the cardiac subpopulation, patisiran treatment led to significant improvement relative to placebo in Norfolk QOL-DN at 18 months, with a LS mean (95% CI)  decrease (improvement) compared to baseline of -3 (-7, 2) points in the patisiran group compared to an LS mean (95% CI) increase (worsening) compared to baseline of 20 (13, 28) points in placebo patients with an overall treatment difference (patisiran –placebo) LS mean (95%CI)  -23 (-32, 14). Additionally, patisiran resulted in improvement across all domains relative to placebo. Detailed data will be presented.

Conclusions:  These results show that treatment with patisiran improved QOL compared to placebo in hATTR amyloidosis patients with evidence of cardiac involvement.  These results are consistent with the outcomes in the overall population, thereby demonstrating that patisiran provides clinical benefit to hATTR amyloidosis patients with both polyneuropathy and cardiomyopathy.

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