Evidence map›Paper›PMID 32641071›Full record

Trial reportOrphanet journal of rare diseases2020

A phase II, open-label, extension study of long-term patisiran treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis.

Teresa Coelho, David Adams, Isabel Conceição, Márcia Waddington-Cruz, Hartmut H Schmidt, Juan Buades, Josep Campistol, John L Berk, Michael Polydefkis, Jing Jing Wang and 4 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Orphanet journal of rare diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01961921 (A Phase 2, Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Safety, Clinical Activity, and Pharmacokinetics of ALN-TTR02 in Patients With Familial Amyloidotic Polyneuropathy Who Have Previously Received ALN-TTR02), which is not on this map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01961921 phase2completednot on this map

A Phase 2, Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Safety, Clinical Activity, and Pharmacokinetics of ALN-TTR02 in Patients With Familial Amyloidotic Polyneuropathy Who Have Previously Received ALN-TTR02

TypeinterventionalSponsorAlnylam PharmaceuticalsRan2013 to 2016Enrolled27ConditionsTTR-mediated AmyloidosisArmsALN-TTR02 (patisiran) administered by intravenous (IV) infusion
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  4. Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022
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  7. Reversing PAI-1 deficiency in blood using mRNA lipid nanoparticles.Molecular therapy. Methods & clinical development · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 11 institutions in 7 countries.

Teresa CoelhoHospital de Santo António, Centro Hospitalar do Porto, 4099-001, Porto, Portugal. tcoelho@netcabo.pt.
David AdamsNational Reference Centre for Familial Amyloidotic Polyneuropathy (NNERF)/APHP/INSERM U 1195/CHU Bicêtre, 78 rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France.
Isabel ConceiçãoHospital de Santa Maria-CHULN, and IMM, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Márcia Waddington-CruzHospital Universitário Clementino Fraga Filho, Federal University of Rio de Janeiro, Ilha do Fundao, Rio de Janeiro, CEP21941-913, Brazil.
Hartmut H SchmidtUniversitätsklinikum Münster, Waldeyerstr. 1, 48149, Munster, Germany.
Juan BuadesFundació Institut d'Investigació Sanitària Illes Balears (IdISBa), Carretera de Valldemossa, 79, Palma de Mallorca 07120, Balearic Islands, Spain; Servicio de Medicina Interna, Hospital Universitario Son Llàtzer, Carretera Manacor KM, 7198, Palma de Mallorca, Balearic Islands, Spain.
Josep CampistolHospital Clinic, University of Barcelona, C/ Villarroel, 170, 8036, Barcelona, Spain.
John L BerkBoston University, 72 East Concord Street, K-504, Boston, 02118, USA.
Michael PolydefkisJohns Hopkins University, 855 North Wolfe Street, Rangos 435, Baltimore, MD, 21205, USA.
Jing Jing WangAlnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA.
Jihong ChenAlnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA.
Marianne T SweetserAlnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA.
Jared GollobAlnylam Pharmaceuticals, 300 Third Street, Cambridge, MA, 02142, USA.
Ole B SuhrUmeå University, Universitetstorget 16, 901 87, Umeå, Sweden.
Alnylam Pharmaceuticals (United States) · USBicêtre Hospital · FRBoston University · USCentro Hospitalar do Porto · PTHealth Research Institute of the Balearic Islands · ESHospital de Santa Maria · PTJohns Hopkins University · USUmeå University · SEUniversidade Federal do Rio de Janeiro · BRUniversitat de Barcelona · ESUniversity Hospital Münster · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatisiran, an RNA interference therapeutic, has demonstrated robust reduction of wild-type and mutant transthyretin protein and was able to improve polyneuropathy and quality of life following 18 months of treatment in patients with hereditary transthyretin-mediated (hATTR) amyloidosis. In this 24-month Phase II open-label extension study, we evaluated the effects of patisiran treatment (0.3 mg/kg intravenously every 3 weeks) on safety, serum transthyretin levels, and clinical parameters. Efficacy assessments included modified Neuropathy Impairment Score +7 (mNIS+7) and multiple disease-relevant measures. Cardiac assessments were performed in a pre-specified cardiac subgroup.

resultsTwenty-seven patients entered this study, including 12 (44%) with ambulation difficulties due to their neuropathy and 11 (41%) who met criteria for the cardiac subgroup. During treatment, the majority of adverse events were mild/moderate in severity; there were no drug-related adverse events leading to treatment discontinuation. The most common drug-related adverse events were flushing and infusion-related reactions (22% each). Patisiran resulted in rapid, robust (~ 82%), and sustained reduction of mean transthyretin levels over 24 months. A mean 6.95-point decrease (improvement) in mNIS+7 from baseline was observed at 24 months. Patisiran's impact on mNIS+7 was irrespective of concomitant tafamidis or diflunisal use, sex, or age. Clinical assessments of motor function, autonomic symptoms, disease stage, and quality of life remained stable over 24 months. No significant changes were observed for echocardiographic measures or cardiac biomarkers in the cardiac subgroup. Exploratory analyses demonstrated improvements in nerve-fiber density with corresponding reductions in amyloid burden observed in skin biopsies over 24 months.

conclusionsLong-term treatment with patisiran had an acceptable safety profile and was associated with halting/improvement of polyneuropathy progression in patients with hATTR amyloidosis.

trial registrationThe study was registered at ClinicalTrials.gov (identifier: NCT01961921 ) on October 14, 2013.

Indexed as

Amyloid Neuropathies, FamilialPrealbuminHumansQuality of LifeRNA, Small InterferingpatisiranPrealbuminRNA, Small InterferingATTR amyloidosisCardiomyopathyPatisiranPolyneuropathyRNA interference

Identifiers

PMID32641071
PMCPMC7341568
OpenAlexW3040733127

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.