RT Journal Article
SR Electronic
T1 PHASE 2 OPEN-LABEL EXTENSION STUDY OF PATISIRAN, AN INVESTIGATIONAL RNAI THERAPEUTIC FOR THE TREATMENT OF FAMILIAL AMYLOID POLYNEUROPATHY
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP e4
OP e4
DO 10.1136/jnnp-2015-312379.27
VO 86
IS 11
A1 David Adams
A1 Ole Suhr
A1 Isabel Conceicao
A1 Marcia Waddington-Cruz
A1 Hartmut Schmidt
A1 Juan Buades
A1 Josep Campistol
A1 Jean Pouget
A1 John Berk
A1 Teresa Coelho
YR 2015
UL http://jnnp.bmj.com/content/86/11/e4.115.abstract
AB 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.