In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.

The free consultation period for this content is over.

It is now only available year-round to HFA Silver & Gold Members, Fellows of the ESC and Young combined Members

Inotersen improves quality of life, polyneuropathy, and cardiomyopathy in patients with hereditary transthyretin amyloidosis: results of the phase 3 study NEURO-TTR

Session Comorbidities and cardiomyopathies - How to manage?

Speaker Carol Whelan

Event : Heart Failure 2018

  • Topic : heart failure
  • Sub-topic : Heart Failure with Preserved Ejection Fraction
  • Session type : Rapid Fire Abstracts

Authors : C Whelan (London,GB), B Drachman (Philadelphia,US), S Heitner (Portland,US), M Maurer (New York,US), T Damy (Creteil,FR), D Judge (Charleston,US), B Monia (Carlsbad,US), S Hughes (Carlsbad,US), J Kwoh (Carlsbad,US), B Jung (Carlsbad,US), E Ackermann (Carlsbad,US), M Benson (Indianapolis,US)

Authors:
C Whelan1 , B Drachman2 , S Heitner3 , M Maurer4 , T Damy5 , D Judge6 , B Monia7 , S Hughes7 , J Kwoh7 , B Jung7 , E Ackermann7 , M Benson8 , 1University College London—National Amyloidosis Centre - London - United Kingdom , 2University of Pennsylvania - Philadelphia - United States of America , 3Oregon Health & Science University - Portland - United States of America , 4Columbia University Medical Center - New York - United States of America , 5Centre Hospitalier Universitaire Henri-Mondor - Creteil - France , 6Medical University of South Carolina - Charleston - United States of America , 7Ionis Pharmaceuticals - Carlsbad - United States of America , 8Indiana University School of Medicine - Indianapolis - United States of America ,

Citation:

INTRODUCTION: Hereditary transthyretin (TTR) amyloidosis (hATTR) is a rare, progressive, and fatal disease caused by misfolded TTR that builds up as amyloid in major organ systems, especially cardiac tissue and nerves, causing cardiomyopathy (CM) and polyneuropathy (PN), respectively. hATTR causes significant morbidity and a progressive decline in patient quality of life.

PURPOSE: To evaluate the efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of TTR protein production, in patients with hATTR with CM and PN.

METHODS: NEURO-TTR (NCT01737398) is a global, randomised, double-blind, placebo-controlled phase 3 study. Adults (n=172) with hATTR-PN (stage 1 or 2) with or without CM were randomly assigned 2:1 and received 300-mg weekly subcutaneous inotersen or placebo for 15 months. CM was defined as diagnosis of hATTR-CM or =1.3 cm interventricular septum thickness (IVS; by echocardiography) at baseline. Primary endpoints were change from baseline to week 66 in the modified Neuropathy Impairment Score+7 (mNIS+7) and Norfolk Quality of Life–Diabetic Neuropathy (Norfolk QOL-DN) total score. Exploratory outcomes included measures of CM, including IVS, left ventricle mass (LVM), and posterior wall thickness (PWT).

RESULTS: At baseline, 69% of patients were male, mean age was 59 years (range, 27-81 years), and 63% (108/172) had CM. Of patients given placebo and inotersen, 55% (33/60) and 67% (75/112), respectively, had CM. Inotersen treatment compared with placebo resulted in significant improvement from baseline to week 66 in mNIS+7 (P<0.0001) and Norfolk QOL-DN total score (P=0.0006) in all patients, irrespective of CM status. The subset of patients with CM also demonstrated significant improvement from baseline to week 66 in mNIS+7 (P<0.001) and Norfolk QOL-DN total score (P=0.036) with inotersen treatment compared with placebo. Patients with significant CM at baseline (IVS =1.5 cm) treated with inotersen compared with placebo also showed significant benefit in IVS (P=0.0150), LVM (P=0.0288), and PWT (P=0.0425). Most adverse events were mild or moderate. Key safety findings of thrombocytopenia and renal events were easily managed and monitored with routine testing.

CONCLUSION: Inotersen demonstrated significant benefits in quality of life and prevention of cardiac and neurological disease progression in patients with hATTR with CM and PN.

The free consultation period for this content is over.

It is now only available year-round to HFA Silver & Gold Members, Fellows of the ESC and Young combined Members

Members get more

Join now
  • 1ESC Professional Members – access all resources from general ESC events 
  • 2ESC Association Members (Ivory, Silver, Gold) – access your Association’s resources
  • 3Under 40 or in training - with a Combined Membership, access all resources
Join now

Our sponsors

ESC 365 is supported by Bayer, Boehringer Ingelheim and Lilly Alliance, Bristol-Myers Squibb and Pfizer Alliance, Novartis Pharma AG and Vifor Pharma in the form of educational grants. The sponsors were not involved in the development of this platform and had no influence on its content.

logo esc

Our mission: To reduce the burden of cardiovascular disease

Who we are