ArticleBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy2019
Assessing the Potential Risk of Cross-Reactivity Between Anti-Bococizumab Antibodies and Other Anti-PCSK9 Monoclonal Antibodies.
Article in BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01968954 (A Phase 3 Double-blind,Randomized, Placebo-controlled,Parallel-group Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 In Subjects With Primary Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events), which is not on this map. Cited by 9 papers.
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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.
A Phase 3 Double-blind,Randomized, Placebo-controlled,Parallel-group Study To Assess The Efficacy, Safety And Tolerability Of Pf-04950615 In Subjects With Primary Hyperlipidemia Or Mixed Dyslipidemia At Risk Of Cardiovascular Events
Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Directed evolution of a stem-helix-targeting antibody enables MERS-CoV cross-neutralization through enhanced binding affinity.PLoS pathogens · 2026Article
- Directed evolution of a stem-helix-targeting antibody enables MERS-CoV cross-neutralization through enhanced binding affinity.bioRxiv : the preprint server for biology · 2025Article
- Population PK/PD modeling of low-density lipoprotein cholesterol response in hypercholesterolemic participants following administration of bococizumab, a potent anti-PCSK9 monoclonal antibody.CPT: pharmacometrics & systems pharmacology · 2023Article
- Review
- Development of a semi-automated MHC-associated peptide proteomics (MAPPs) method using streptavidin bead-based immunoaffinity capture and nano LC-MS/MS to support immunogenicity risk assessment in drug development.Frontiers in immunology · 2023Article
- Interference in a Neutralizing Antibody Assay for Odronextamab, a CD20xCD3 Bispecific mAb, from Prior Rituximab Therapy and Possible Mitigation Strategy.The AAPS journal · 2022Article
- Antitumor activity and molecular mechanism of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition.Naunyn-Schmiedeberg's archives of pharmacology · 2022Review
- From Genetics to Epigenetics: Top 4 Aspects for Improved SARS-CoV-2 Vaccine Designs as Paradigmatic Examples.Global medical genetics · 2022Review
- Potential dual inhibitors of PCSK-9 and HMG-R from natural sources in cardiovascular risk management.EXCLI journal · 2022Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnti-drug antibodies (ADAs) to bococizumab were detected in > 40% of subjects in the SPIRE lipid-lowering trials. The risk of cross-reactivity between anti-bococizumab antibodies and other approved anti-proprotein convertase subtilisin/kexin type-9 (PCSK9) monoclonal antibodies (mAbs) was investigated using a single-assay approach.
methodsBococizumab immunogenicity was assessed in SPIRE-HR, a 52-week study. The highest ADA titer sample from each ADA-positive subject (n = 155) was tested in vitro for cross-reactivity to alirocumab and evolocumab using a novel ADA assay approach. Additional specificity tiers within the bococizumab ADA assay against each drug were validated using recombinant PCSK9 as a surrogate cross-reactive positive control. If the highest ADA titer sample showed cross-reactivity, additional samples from that subject were analyzed. Cross-reactivity was determined by the ability of alirocumab or evolocumab to inhibit the sample signal greater than or equal to the cross-reactivity cut-points.
resultsADAs were detected in 44.0% (155/352) of bococizumab-treated subjects, and 27.0% also developed neutralizing antibodies (NAbs). Median ADA and NAb titers ranged from 276 to 526 and 8 to 12 over the course of the study, respectively. From 155 ADA-positive subjects tested for cross-reactivity, one (0.6%) subject showed weak cross-reactivity to both alirocumab and evolocumab. This cross-reactivity signal was transient (from Days 337 to 373) and undetectable at the last ADA-positive timepoint (Day 407).
conclusionA novel, single-assay approach was validated to assess the potential cross-reactivity of anti-bococizumab antibodies to alirocumab and evolocumab. In subjects who developed ADAs to bococizumab, the likelihood of clinically relevant cross-reactivity to marketed anti-PCSK9 mAbs is remote, based on the low frequency of cross-reactivity observed, which was weak in signal inhibition and transient in nature. CLINICAL
trial registrationThe SPIRE-HR study is registered on ClinicalTrials.gov under the identifier NCT01968954.
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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.