Related Experiment Video
Updated: Jul 12, 2025
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis
Mathew S Maurer1, Parag Kale1, Marianna Fontana1
1From Columbia University Irving Medical Center (M.S.M.) and Grossman School of Medicine, NYU Langone (A.G.-D.) - both in New York; the Center for Advanced Heart and Lung Disease, Baylor University Medical Center (P.K., R.L.G.), Baylor Scott & White Research Institute, and Texas A&M Health Science Center, Dallas (R.L.G.), and TCU School of Medicine, Fort Worth (R.L.G.) - all in Texas; the National Amyloidosis Centre, UCL, Division of Medicine, Royal Free Hospital, London (M.F., J.D.G.); Boston University School of Medicine (J.L.B.), the Cardiovascular Division, Brigham and Women's Hospital (S.D.S., M.D.C.), and the Division of Nuclear Medicine and Molecular Imaging, Brigham and Women's Hospital, Harvard Medical School (M.D.C.), Boston, and Alnylam Pharmaceuticals, Cambridge (P.B., M.T.W., J.C., E.Y., M.T.S., P.Y.J., P.P.G., J.V.) - all in Massachusetts; the Department of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN (M.G.); the Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen (F.G.), and the Department of Cardiology, Aarhus University Hospital, Aarhus (S.H.P.) - both in Denmark; the Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville (R.R.H.); the Cardiology Department and French National Reference Center for Cardiac Amyloidosis, GRC Amyloid Research Institute and Clinical Investigation Centre 1430 at Hôpitaux Universitaires Henri-Mondor Assistance Publique-Hôpitaux de Paris, and IMRB, INSERM, Université Paris Est Creteil, Creteil (T.D.), and INSERM, LTSI UMR 1099, Centre Hospitalier Universitaire de Rennes, Rennes (E.D.) - both in France; Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City (A.G.-D.); the Department of Medicine, University of Chicago, Chicago (N.S.); the Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto (Y.S.), the Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume (N.T.), and the Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (K.T.) - all in Japan; Westmead Amyloidosis Service, Westmead Hospital, Sydney (M.S.T.); the Department of Cardiology, Institute for Clinical and Experimental Medicine (M.K.), and the 2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague (T.P.) - both in Prague, Czech Republic; the Heart Vascular and Thoracic Institute, Cleveland Clinic, Cleveland (W.H.W.T.); Taipei Veterans General Hospital and National Yang Ming Chiao Tung University, Taipei, Taiwan (W.-C.Y.); Amyloidosis Research & Treatment Center, Fondazione IRCCS Policlinico San Matteo di Pavia, Pavia (L.O.), the Department of Medical and Surgical Sciences, University of Bologna, and the Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna (I.D.), and the Department of Clinical and Experimental Medicine, Careggi University Hospital, Florence (F.P.) - all in Italy; and Unidade de Pesquisa Clínica-UPC, Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto-USP (M.S.), and Instituto do Coração-HCFMUSP (F.F.) - both in São Paulo.
Background:
Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin.
Methods:
In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months.
Results:
A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group.
Conclusions:
In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.).
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