Evidence map›Paper›PMID 41012095›Full record

ArticleVaccines2025

Peptide-Based Anti-PCSK9 Product for Long-Lasting Management of Hypercholesterolemia.

Suresh R Giri, Akshyaya Chandan Rath, Chitrang J Trivedi, Bibhuti Bhusan Bhoi, Sandip R Palode, Vighnesh N Jadhav, Hitesh Bhayani, Avanishkumar Singh, Chintan Patel, Tushar M Patel and 9 more

Abstract read
In one paragraph

Article in Vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  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

19 authors.

Suresh R GiriDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.ORCID 0000-0003-0063-5738
Akshyaya Chandan RathDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.ORCID 0009-0004-6443-8826
Chitrang J TrivediDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Bibhuti Bhusan BhoiDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Sandip R PalodeDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Vighnesh N JadhavDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.ORCID 0009-0005-1170-530X
Hitesh BhayaniDepartment of Cell Biology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Avanishkumar SinghDepartment of Biotechnology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Chintan PatelDepartment of Biotechnology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Tushar M PatelDepartment of Biotechnology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Niraj M SakhraniDepartment of Biotechnology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Jitendra H PatelDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Niraj A ShahDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Rajendra ChopadeDepartment of Medicinal Chemistry, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Rajesh BahekarDepartment of Medicinal Chemistry, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Vishwanath PawarDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Rajesh SundarDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Sanjay BandyopadhyayDepartment of Biotechnology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.
Mukul R JainDepartment of Pharmacology and Toxicology, Zydus Research Centre, Zydus Lifesciences Ltd., Ahmedabad 382213, India.ORCID 0000-0001-5730-1435

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

objectivesHypercholesterolemia remains a major risk factor for cardiovascular disease and a leading cause of global mortality. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptors (LDLR), thereby reducing LDL-cholesterol (LDL-C) clearance. While monoclonal antibodies (mAbs) targeting PCSK9 are effective, their short half-life requires frequent dosing and incurs high treatment costs. This study evaluates a novel peptide-based Anti-PCSK9 product aimed at providing sustained LDL-C reduction.

methodsA novel PCSK9 based-peptide conjugated to diphtheria toxoid (DT) was evaluated in various preclinical models: high-fat diet-fed C57BL/6 mice, APOB100/hCETP transgenic mice, BALB/c mice and normocholesterolemic non-human primates. Immunogenicity (Anti-PCSK9 antibody titers, binding affinity by SPR), pharmacodynamics (LDL-C levels, inhibition of PCSK9-LDLR interaction) and safety were assessed. Toxicity was evaluated in rodents, rabbits and dogs through clinical monitoring, histopathology, organ function and safety pharmacology studies.

resultsThe Anti-PCSK9 product induced robust and long-lasting immune response in all models antibody titers in BALB/c mice peaked by week 6 and persisted for 12 months. LDL-C reductions of 44% in APOB100/hCETP mice and 37% in C57BL/6 mice correlated with high antibody titers and strong PCSK9-binding affinities (85 and 49 RU), leading to 59% and 58% inhibition of PCSK9-LDLR interaction, respectively. Non-human primates showed sustained responses. No systemic toxicity was observed; injection-site reactions were mild and reversible. No adverse effects were detected on cardiovascular, neurological, or respiratory systems.

conclusionsThis peptide-based Anti-PCSK9 therapy offers sustained efficacy and safety, representing a promising long-acting alternative for managing hypercholesterolemia.

Indexed as

hypercholesterolemiaimmunizationPCSK9peptide-based therapy

Identifiers

PMID41012095
PMCPMC12474352

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