Article Text

PDF
027
PHASE 2 OPEN-LABEL EXTENSION STUDY OF PATISIRAN, AN INVESTIGATIONAL RNAI THERAPEUTIC FOR THE TREATMENT OF FAMILIAL AMYLOID POLYNEUROPATHY
  1. David Adams1,
  2. Ole Suhr2,
  3. Isabel Conceicao3,
  4. Marcia Waddington-Cruz4,
  5. Hartmut Schmidt5,
  6. Juan Buades6,
  7. Josep Campistol7,
  8. Jean Pouget8,
  9. John Berk9,
  10. Teresa Coelho10
  1. 1Centre Paris-Sud, APHP, Hopital de Bicetre, INSERM U788, Service de Neurologie, France
  2. 2Umea University, Umea, Sweden
  3. 3Centro Hospitalar Lisboa Norte-Hospital de Santa Maria, Lisbon, Portugal
  4. 4Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, Brazil
  5. 5The University Hospital of Muenster, Germany
  6. 6Hospital Son Llatzer, Palma de Mallorca, Spain
  7. 7Hospital Clinic, Barcelona, Spain
  8. 8Centre de Reference des Maladies Naueromusculaires et de la SLA, Hopital de la Timone, France
  9. 9Amyloidosis Center, Boston University, Boston, MA, USA
  10. 10Unidade Clinica de Paramiloidose, Hospital de Santo Antonio, Porto, Portugal

Abstract

Familial amyloid polyneuropathy (FAP) is a progressive disease. Patisiran is an investigational small interfering RNA (siRNA) targeting TTR. The primary objective of the Phase 2 study is to evaluate the safety of 0.3 mg/kg patisiran administered intravenously once every 3 weeks. Twenty-seven patients were enrolled; the mean duration of treatment was 7 months (range 3–12), with 282 doses administered (median of 11 doses/patient). Chronic dosing with patisiran has been generally well tolerated. Two patients experienced serious adverse events regarded as being unrelated to study drug. Infusion-related reactions were observed in 14.8% of the patients, were mild in severity, and did not result in any discontinuations. Sustained TTR lowering of at least 80% was achieved based on serial TTR measurements for over 9 months, with further nadir of up to 89.6% between doses. Neurologic impairment scores were stable after 6 months of treatment with patisiran. A mean decrease from baseline in mNIS+7 of 0.95 points (N=19) observed in this study compared favorably to the estimated increase of 7–10 points in mNIS+7 at 6 months from prior FAP studies in a patient population with similar baseline NIS values. Dosing continues in all patients, and 12–month results will be presented.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.