Evidence map›Paper›PMID 37639169›Full record

ArticleClinical pharmacokinetics2023

Pharmacokinetics and Pharmacodynamics of Patisiran in Patients with hATTR Amyloidosis and with Polyneuropathy After Liver Transplantation.

Prajakta Badri, Bahru Habtemariam, Megan Melch, Valerie A Clausen, Seth Arum, Xingyu Li, Patrick Y Jay, John Vest, Gabriel J Robbie

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03862807 (An Open-label Study to Evaluate Safety, Efficacy and Pharmacokinetics), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.6field-weighted citation impact, top 30% 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.

NCT03862807 phase3completednot on this map

An Open-label Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of Patisiran-LNP in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) With Disease Progression Post-Orthotopic Liver Transplant

TypeinterventionalSponsorAlnylam PharmaceuticalsRan2019 to 2020Enrolled24ConditionsAmyloidosis, Familial, Transthyretin AmyloidosisArmsPatisiran
3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Review
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

9 authors at 1 institution in 2 countries.

Prajakta BadriClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, 101 Main Street, Cambridge, MA, 02142, USA. pbadri@alnylam.com.ORCID 0000-0003-1248-616X
Bahru HabtemariamClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, 101 Main Street, Cambridge, MA, 02142, USA.
Megan MelchClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, 101 Main Street, Cambridge, MA, 02142, USA.
Valerie A ClausenClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, 101 Main Street, Cambridge, MA, 02142, USA.
Seth ArumClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, 101 Main Street, Cambridge, MA, 02142, USA.
Xingyu LiClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, 101 Main Street, Cambridge, MA, 02142, USA.
Patrick Y JayClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, 101 Main Street, Cambridge, MA, 02142, USA.
John VestClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, 101 Main Street, Cambridge, MA, 02142, USA.
Gabriel J RobbieClinical Pharmacology and Pharmacometrics, Alnylam Pharmaceuticals, 101 Main Street, Cambridge, MA, 02142, USA.
Alnylam Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveVariants of the transthyretin (TTR) gene cause hereditary transthyretin-mediated (hATTR) amyloidosis, or ATTRv amyloidosis (v for variant), which results from deposition of misfolded TTR protein as amyloid in organs and tissues. Patisiran is an RNA interference (RNAi) therapeutic that suppresses the hepatic production of TTR protein. Patisiran improves multiple clinical manifestations of hATTR amyloidosis in patients without liver transplantation (LT). Because the liver is the predominant source of circulating TTR, LT has been prescribed to eliminate the production of the variant TTR. However, the continued production of wild-type TTR can contribute to disease progression after LT. Patisiran could potentially address an unmet need in these affected patients. This clinical trial was conducted to evaluate the safety, efficacy, and pharmacokinetics (PK) and pharmacodynamics (PD) of patisiran in patients with hATTR amyloidosis with polyneuropathy progression after LT. In this paper, we describe the PK/PD of patisiran in post-LT patients and compare it with prior patisiran studies in healthy subjects and patients without LT.

methodsIn an open-label study, patients (N = 23) with hATTR amyloidosis with polyneuropathy progression after LT received 0.3 mg/kg patisiran intravenously every 3 weeks (q3w) for 12 months. As a post hoc analysis, the PK and PD results from the current study were compared with prior patisiran studies in healthy volunteers from a Phase 1 study and in patients with hATTR amyloidosis without LT from Phase 2 and 3 studies.

resultsThe PK profile of patisiran siRNA (ALN-18328) and its 2 lipid excipients, DLin-MC3-DMA and PEG2000-C-DMG, in hATTR amyloidosis patients after LT was consistent with prior patisiran studies in non-LT subjects. Plasma PK profiles of ALN-18328 and DLin-MC3-DMA exhibited 2 phases, the first characterized by a short distribution half-life and the second by a minor peak and relatively long elimination half-life. The plasma concentrations of PEG

conclusionsThe consistency of patisiran PK and PD between patients with and without LT suggests that neither LT nor concomitantly administered immunosuppressants influence hepatic uptake or RNAi activity of patisiran. The patisiran dosing regimen of 0.3 mg/kg q3w is appropriate for hATTR amyloidosis patients with or without LT. CLINICAL TRIAL REGISTRATION NO: NCT03862807.

Indexed as

AmyloidosisLiver TransplantationHumansPrealbuminRNA, Small InterferingpatisiranPrealbuminRNA, Small Interfering

Identifiers

PMID37639169
OpenAlexW4386208932

What OpenQuestion holds

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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.