Annabel K. Wang (United States of America)
University of California, Irvine Department of NeurologyAuthor Of 1 Presentation
EFFICACY AND SAFETY WITH >3 YEARS OF INOTERSEN TREATMENT FOR THE POLYNEUROPATHY OF HEREDITARY TRANSTHYRETIN AMYLOIDOSIS
- Laura P. Obici (Italy)
Abstract
Background and Aims:
Hereditary transthyretin amyloidosis (hATTR), a progressive, debilitating, and ultimately fatal disease, causes multisystem dysfunction. We report long-term efficacy and safety for inotersen, an antisense oligonucleotide inhibitor of transthyretin protein production.
Methods:
Patients completing the NEURO-TTR trial (NCT01737398) enrolled in its open-label extension (OLE; NCT02175004). Assessments included modified Neuropathy Impairment Score +7 (mNIS+7), Norfolk Quality of Life–Diabetic Neuropathy questionnaire (Norfolk QOL-DN), and safety monitoring. As of July 28, 2020, efficacy is reported for patients from Europe and North America and safety is reported for all patients.
Results:
Patients who switched from placebo to inotersen in the OLE (n=39) demonstrated slowing of neurologic disease progression compared with natural history (based on placebo projection); mean mNIS+7 and Norfolk QOL-DN scores at OLE baseline/1/2/3 years were 102.7/111.2/113.6/112.3 and 61.2/59.0/63.5/67.7, respectively. Patients receiving inotersen for 51 months (15 months in NEURO-TTR + 36 months in OLE; n=67) continued to show benefit, with mean mNIS+7 and Norfolk QOL-DN scores at OLE baseline/1/2/3 years of 84.3/90.7/98.1/95.1 and 50.3/52.4/53.1/57.2, respectively. Few patients (6/135; 4.4%) had serious treatment-related adverse events; no treatment-related deaths occurred. Under enhanced monitoring, there have been no reports of grade 4 thrombocytopenia or acute glomerulonephritis despite increased duration of exposure. No new safety concerns were identified.
Conclusions:
Extended treatment with inotersen for over 3 years slowed progression of the polyneuropathy associated with hATTR, with neurologic preservation observed in patients who initiated inotersen earlier, highlighting the importance of early treatment. Enhanced monitoring has reduced risks of severe thrombocytopenia and acute glomerulonephritis.