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  1. Hartmut Schmidt1,
  2. David Adams2,
  3. Teresa Coelho3,
  4. Isabel Conceicao4,
  5. Marcia Waddington-Cruz5,
  6. Juan Buades6,
  7. Josep Campistol7,
  8. Jean Pouget8,
  9. Jared Gollob9,
  10. Ole Suhr10
  1. 1 University Hospital of Muenster, Muenster, Germany
  2. 2 Centre Paris-Sud, APHP, Hopital de Bicetre, France
  3. 3 Hospital de Santo Antonio, Porto, Portugal
  4. 4 Centro Hospitalar Lisboa Norte-Hospital de Santa Maria, Lisbon, Portugal
  5. 5 Hospital Universitario Clementino Fraga Filho, Rio De Janeiro, Brazil
  6. 6 Hospital Son Llatzer, Palma de Mallorca, Spain
  7. 7 Hospital Clinic, Barcelona, Spain
  8. 8 Hopital de la Timone, Marseille, France
  9. 9 Alnylam Pharmaceuticals, Cambridge USA
  10. 10 Umea University, Sweden


Background Familial Amyloid Polyneuropathy (FAP) is a progressive disease caused by deposition of transthyretin (TTR). Patisiran is an investigational, small interfering RNA (siRNA) inhibiting TTR. This abstract highlights patisiran's long-term safety.

Methods Phase 2 OLE study to evaluate patisiran's safety. Patisiran's effect on serum TTR levels, impact on neuropathy impairment scores and QOL were assessed.

Results 27 patients with FAP enrolled; median age 64 years. Patisiran was generally well tolerated out to 23-months. Five patients experienced SAEs (unrelated) including one discontinuation (gastroesophageal cancer); patient subsequently died. Flushing (25.9%) and infusion-related reactions (18.5%) were mild in severity; no discontinuations resulted. Approximately 80% sustained mean serum TTR lowering resulted with a mean nadir of up to 93% between doses. Among the 20 evaluable patients, neuropathy impairment scores were stable through 18-months; mean change in mNIS+7 and NIS of 1.7 and 4.2 points, respectively. This compares favorably to 17–26 point mNIS+7/NIS increase estimated at 18-months from prior FAP studies. Stabilization of QOL measures and improvement of distal thigh sweat gland nerve fiber density observed.

Conclusion Data demonstrates that 18-months of patisiran administration was generally well tolerated, resulted in sustained mean serum TTR lowering, supporting the hypothesis that TTR knockdown potentially halts neuropathy progression.

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