Evidence map›Paper›PMID 27959715›Full record

Trial reportThe New England journal of medicine2017

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9.

Kevin Fitzgerald, Suellen White, Anna Borodovsky, Brian R Bettencourt, Andrew Strahs, Valerie Clausen, Peter Wijngaard, Jay D Horton, Jorg Taubel, Ashley Brooks and 5 more

Registry-linked trialAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02314442 (A Phase 1, Randomized, Single Blind, Placebo Controlled, Single Ascending Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN PCSSC in Subjects With Elevated Low Density Lipoprotein Cholesterol), which is not on this map. Cited by 325 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
325citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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.

NCT02314442 phase1completednot on this map

A Phase 1, Randomized, Single Blind, Placebo Controlled, Single Ascending Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN PCSSC in Subjects With Elevated Low Density Lipoprotein Cholesterol

TypeinterventionalSponsorAlnylam PharmaceuticalsRan2014 to 2015Enrolled70ConditionsHypercholesterolemiaArmsALN-PCSSC, Sterile Normal Saline (0.9% NaCl)
3 · Its place in the literature

Who cites it

325 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. A Meta-analysis of the Regulation of Low-Density Lipoprotein Cholesterol and Proprotein Convertase Subtilisin-Kexin Type 9 with Inclisiran.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025 · on this map
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. The promising novel therapies for familial hypercholesterolemia.Journal of clinical laboratory analysis · 2022
    Pooled it
  6. Biotechnology Approaches for the Treatment of Dyslipidemia.Cardiovascular drugs and therapy · 2021
    Pooled it
  7. Trial
  8. Trial
  9. Trial
  10. Towards mRNA therapeutics 2.0.Nature reviews. Drug discovery · 2026
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

265 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Kevin FitzgeraldFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Suellen WhiteFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Anna BorodovskyFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Brian R BettencourtFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Andrew StrahsFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Valerie ClausenFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Peter WijngaardFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Jay D HortonFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Jorg TaubelFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Ashley BrooksFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Chamikara FernandoFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Robert S KauffmanFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
David KallendFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Akshay VaishnawFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).
Amy SimonFrom Alnylam Pharmaceuticals, Cambridge, MA (K.F., S.W., A. Borodovsky, B.R.B., A. Strahs, V.C., R.S.K., A.V., A. Simon); the Medicines Company, Parsippany, NJ (P.W., D.K.); University of Texas Southwestern Medical Center, Dallas (J.D.H.); Richmond Pharmacology, St. George's University of London, London (J.T.); and Covance Clinical Research Unit, Leeds, United Kingdom (A. Brooks, C.F.).

Funding

TRANSCRIPTIONAL REGULATION OF LDL RECEPTOR PROMOTERP01HL020948 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI GOLDSTEIN, JOSEPH L · 1985 to 2021
$103.1M
NHLBI NIH HHS P01 HL020948
6 · The paper itself

Abstract

backgroundInclisiran (ALN-PCSsc) is a long-acting RNA interference (RNAi) therapeutic agent that inhibits the synthesis of proprotein convertase subtilisin-kexin type 9 (PCSK9), a target for the lowering of low-density lipoprotein (LDL) cholesterol.

methodsIn this phase 1 trial, we randomly assigned healthy volunteers with an LDL cholesterol level of at least 100 mg per deciliter in a 3:1 ratio to receive a subcutaneous injection of inclisiran or placebo in either a single-ascending-dose phase (at a dose of 25, 100, 300, 500, or 800 mg) or a multiple-dose phase (125 mg weekly for four doses, 250 mg every other week for two doses, or 300 or 500 mg monthly for two doses, with or without concurrent statin therapy); each dose cohort included four to eight participants. Safety, the side-effect profile, and pharmacodynamic measures (PCSK9 level, LDL cholesterol level, and exploratory lipid variables) were evaluated.

resultsThe most common adverse events were cough, musculoskeletal pain, nasopharyngitis, headache, back pain, and diarrhea. All the adverse events were mild or moderate in severity. There were no serious adverse events or discontinuations due to adverse events. There was one grade 3 elevation in the γ-glutamyltransferase level, which was considered by the investigator to be related to statin therapy. In the single-dose phase, inclisiran doses of 300 mg or more reduced the PCSK9 level (up to a least-squares mean reduction of 74.5% from baseline to day 84), and doses of 100 mg or more reduced the LDL cholesterol level (up to a least-squares mean reduction of 50.6% from baseline). Reductions in the levels of PCSK9 and LDL cholesterol were maintained at day 180 for doses of 300 mg or more. All multiple-dose regimens reduced the levels of PCSK9 (up to a least-squares mean reduction of 83.8% from baseline to day 84) and LDL cholesterol (up to a least-squares mean reduction of 59.7% from baseline to day 84).

conclusionsIn this phase 1 trial, no serious adverse events were observed with inclisiran. Doses of 300 mg or more (in single or multiple doses) significantly reduced levels of PCSK9 and LDL cholesterol for at least 6 months. (Funded by Alnylam Pharmaceuticals and the Medicines Company; ClinicalTrials.gov number, NCT02314442 .).

Indexed as

PCSK9 InhibitorsRNAi TherapeuticsAcetylgalactosamineAdolescentAdultAgedAnticholesteremic AgentsCholesterol, LDLFemaleHealthy VolunteersHumansInjections, SubcutaneousMaleMiddle AgedProprotein Convertase 9RNA-Induced Silencing ComplexAcetylgalactosamineALN-PCSAnticholesteremic AgentsCholesterol, LDLPCSK9 InhibitorsPCSK9 protein, humanProprotein Convertase 9RNA-Induced Silencing ComplexRNA, Small Interfering

Identifiers

PMID27959715
PMCPMC5778873

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.