Dataset Information

Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.

ABSTRACT: The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreover, toxicokinetic evaluation in a repeat-dose rat study and human tissue cross-reactivity study reveals a favorable pharmacokinetic profile of CSX-1004 with no safety-related issues. Using a highly translational non-human primate (NHP) model of respiratory depression, we demonstrate CSX-1004-mediated protection from repeated fentanyl challenges for 3-4 weeks. Furthermore, treatment with CSX-1004 produces up to a 15-fold potency reduction of fentanyl in NHP respiration, antinociception and operant responding assays without affecting non-fentanyl opioids like oxycodone. Taken together, our data establish the feasibility of CSX-1004 as a promising candidate medication for preventing and reversing fentanyl-induced overdose.

SUBMITTER: Bremer PT

PROVIDER: S-EPMC10698161 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.

Bremer Paul T PT Burke Emily L EL Barrett Andrew C AC Desai Rajeev I RI

Nature communications 20231205 1

The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreov ...[more]

PMID: 38052779

Similar Datasets

Project description:BackgroundDrug overdose mortality continues to increase, now driven by fentanyl. Prevention tools such as naloxone and medications to treat opioid use disorder are not sufficient to control overdose rates; additional strategies are urgently needed.ObjectiveWe sought to adapt a behavioral intervention to prevent opioid overdose (repeated-dose behavioral intervention to reduce opioid overdose [REBOOT]) that had been successfully piloted in San Francisco, California, United States, to the setting of Boston, Massachusetts, United States, and the era of fentanyl for a full efficacy trial.MethodsWe used the assessment, decision, adaptation, production, topical experts, integration, training, and testing (ADAPT-ITT) framework for intervention adaptation. We first identified opioid overdose survivors who were actively using opioids as the population of interest and REBOOT as the intervention to be adapted. We then performed theater testing and elicited feedback with 2 focus groups (n=10) in Boston in 2018. All participants had used opioids that were not prescribed to them in the past year and experienced an opioid overdose during their lifetime. We incorporated focus group findings into our initial draft of the adapted REBOOT intervention. The adapted intervention was reviewed by 3 topical experts, and their feedback was integrated into a subsequent draft. We trained study staff on the intervention and made final refinements based on internal piloting. This paper describes the overall ADAPT-ITT process for intervention adaptation, as well as a qualitative analysis of the focus groups. Working independently, 2 authors (VMM and JA) reviewed the focus group transcripts and coded them for salient and common themes using the constant comparison method, meeting to discuss any discrepancies until consensus was reached. Codes and themes were then mapped onto the REBOOT counseling steps.ResultsFocus group findings contributed to substantial changes in the counseling intervention to better address fentanyl overdose risk. Participants described the widespread prevalence of fentanyl and said that, although they tried to avoid it, avoidance was becoming impossible. Using alone and lower opioid tolerance were identified as contributors to overdose risk. Slow shots or tester shots were acceptable and considered effective to reduce risk. Naloxone was considered an effective reversal strategy. Although calling emergency services was not ruled out, participants described techniques to prevent the arrival of police on the scene. Expert review and internal piloting improved the intervention manual through increased participant centeredness, clarity, and usability.ConclusionsWe successfully completed the ADAPT-ITT approach for an overdose prevention intervention, using theater testing with people who use opioids to incorporate the perspectives of people who use drugs into a substance use intervention. In the current crisis, overdose prevention strategies must be adapted to the context of fentanyl, and innovative strategies must be deployed, including behavioral interventions.Trial registrationClinicalTrials.gov NCT03838510; https://clinicaltrials.gov/ct2/show/NCT03838510.

Dataset Information

Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.

Publications

Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets