enibarcimab (HAM8101) / Adrenomed - LARVOL DELTA

Enibarcimab for the treatment of septic shock in patients selected by a combination of the biomarkers bio-ADM and DPP3: A prespecified subgroup analysis of the AdrenOSS-2 trial. (PubMed, J Crit Care) - No abstract available

Biomarker • Journal • Septic Shock

Recent advances of precision immunotherapy in sepsis. (PubMed, Burns Trauma) - "Suggested strategies to attenuate the immune responses are anakinra, nangibotide and tocilizumab...Suggested strategies to restore SII are nivolumab, recombinant human interferon-gamma, CYT107, granulocyte macrophage colony stimulating factor and IgM-enriched immunoglobulin prepapations. Biomarkers that guide their use are the expression of the human leukocyte antigen DR on blood monocytes, the absolute lymphocyte count and blood levels of immunoglobulin M. One recently suggested strategy to restore vascular tone is adrecizumab, the use of which is guided by blood levels of bio-adrenomedulin. The use of these precision treatment strategies is still hampered by the need for large-scale randomized controlled trials."

IO biomarker • Journal • Review • Infectious Disease • Septic Shock • CRP • IFNG

The ADESTE trial: A phase 2 study of enibarcimab, a monoclonal antibody targeting adrenomedullin, in acute heart failure. (PubMed, ESC Heart Fail) - "In this pilot safety study of patients hospitalized for AHF, IV infusion of EN 0.5 and 2 mg/kg increased circulating plasma bio-ADM levels and was well-tolerated without treatment-related SAEs occurring during hospitalization and up to 90 days after discharge."

Journal • P2 data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension • ADM

Enhancing sepsis biomarker development: key considerations from public and private perspectives. (PubMed, Crit Care) - "Biomarker-guided interventions for sepsis to identify patients that would benefit more from therapy, such as sTREM-1-guided Nangibotide treatment or Adrenomedullin-guided Enibarcimab treatment, appear promising but require further evaluation. Artificial intelligence also has great potential in the sepsis biomarker discovery field through capability to analyse high volume complex data and identify complex multiparametric patient endotypes or trajectories. To conclude, biomarker development in sepsis requires (i) a comprehensive and multidisciplinary approach employing the most advanced analytical tools, (ii) the creation of a platform that collaboratively merges scientific and commercial needs and (iii) the support of an expedited regulatory approval process."

Biomarker • Journal • Review • Critical care • Infectious Disease • Pediatrics • Septic Shock • ADM

AdrenoMed Receives FDA Fast Track Designation for Enibarcimab for Treatment of Septic Shock (GlobeNewswire) - "AdrenoMed AG...announced that the US Food and Drug Administration (FDA) has granted Fast Track designation to its lead product candidate enibarcimab, a first-in-class non-neutralizing monoclonal antibody, for the treatment of septic shock. AdrenoMed is now preparing a confirmatory Phase IIb/III clinical trial to confirm the reduced septic shock mortality under enibarcimab treatment employing a precision medicine approach."

Fast track designation • Cardiovascular • Septic Shock

Elevated dipeptidyl peptidase 3 predicts morbidity and mortality in cardiogenic shock: pre-specified secondary analyses from the accost-hh trial (ISICEM 2024) - " The investigator -initiated, multi -center, placebo -controlled, phase 2 study ACCOST -HH was the very first clinical trial to evaluate a monoclonal antibody, Adrecizumab, in cardiogenic shock [1]... Circulating DPP3 is a strong predictor of morbidity and mortality in cardiogenic shock. The results need to be validated in further cardiogenic shock cohorts, but otherwise hold strong promise for the upcoming clinical trials on the evaluation of the specific DPP3 -antibody Procizumab as new breakthrough therapy in cardiogenic shock."

Cardiovascular

Precision medicine in septic shock with enibarcimab – biomarker guided definition of target population (ISICEM 2024) - "These previously unpublished data from the AdrenOSS -2 trial show that a precision medicine approach using bio-ADM and cDPP3 for patient selection can overcome patient heterogeneity in septic shock leading to improved mortality."

Biomarker • Clinical • Septic Shock

AGNES-19: Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial (clinicaltrials.gov) - P2 | N=16 | Terminated | Sponsor: Universitätsklinikum Hamburg-Eppendorf | N=180 ➔ 16 | Recruiting ➔ Terminated; Due to poor recruitment.

Biomarker • Enrollment change • Trial termination • Infectious Disease • Novel Coronavirus Disease

AGNES-19: Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Universitätsklinikum Hamburg-Eppendorf | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2023 ➔ Dec 2023 | Initiation date: Jul 2022 ➔ Oct 2022 | Trial primary completion date: Mar 2023 ➔ Sep 2023

Biomarker • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Effects of enrichment strategies on outcome of adrecizumab treatment in septic shock: Post-hoc analyses of the phase II adrenomedullin and outcome in septic shock 2 trial. (PubMed, Front Med (Lausanne)) - "In contrast, treatment timing was not significantly associated with 28-day mortality in multivariate interaction analyses. In septic shock patients with high ADM levels, a further post-hoc enrichment strategy based on cDPP3 may indicate (with all the caveats to be considered for post-hoc subgroup analyses) that therapeutic efficacy is most pronounced in patients with lower cDPP3 levels."

Journal • P2 data • Retrospective data • Cardiovascular • Infectious Disease • Septic Shock • ADM

AGNES-19: Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial (clinicaltrials.gov) - P2 | N=180 | Not yet recruiting | Sponsor: Universitätsklinikum Hamburg-Eppendorf | Trial completion date: Jun 2023 ➔ Sep 2023 | Initiation date: Mar 2022 ➔ Jul 2022 | Trial primary completion date: Dec 2022 ➔ Mar 2023

Biomarker • Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Rethinking Boosters and Personal Responsibility as Pandemic Enters New Phase (BioSpace) - "Dr. Peter Chin-Hong...echoed the idea, saying, 'If we settle down to one shot per year that combines COVID and flu, I think that will be sustainable. Nobody will want to get a vaccine every six months. So we have to change the strategy.'"

Media quote • Novel Coronavirus Disease • DPP3

International clinical research of critical care medicine in 2021 (PubMed, Zhonghua Wei Zhong Bing Ji Jiu Yi Xue) - "However, we also encounter negative results such as balanced solution during fluid resuscitation, hypothermia therapy after out-of-hospital cardiac arrest or traumatic brain injury, adrenomedullin-specific antibody adrecizumab therapy and coupled plasma filtration-adsorption (CPFA) therapy for patients with septic shock, extracorporeal carbon dioxide removal (ECCOR) implementation in acute hypoxic respiratory failure, continuous infusion of hypertonic saline in patients with traumatic brain injury. Collectively, in the future, individualized diagnosis and management based on the principle of "wise choice" will become the daily practice scene for all intensivists."

Journal • Acute Respiratory Distress Syndrome • Anesthesia • Cardiovascular • CNS Disorders • Critical care • Infectious Disease • Myocardial Infarction • Pulmonary Disease • Respiratory Diseases • Septic Shock • Vascular Neurology • ADM

Adrecizumab? (ISICEM 2022) - No abstract available

AGNES-19: Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial (clinicaltrials.gov) - P2 | N=218 | Not yet recruiting | Sponsor: Universitätsklinikum Hamburg-Eppendorf | Phase classification: P2/3 ➔ P2 | Initiation date: Dec 2021 ➔ Mar 2022

Biomarker • Phase classification • Trial initiation date • Infectious Disease • Novel Coronavirus Disease

Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases. (PubMed, Hypertens Res) - "Accordingly, these derivatives will reduce the inconvenience in use compared to that for native AM and expand the possible applications of AM for treating CVDs. In this review, we present the latest translational status of AM and its derivatives."

Journal • Review • Cardiovascular • CNS Disorders • Congestive Heart Failure • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hypertension • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Myocardial Infarction • Peripheral Arterial Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Septic Shock • ADM

Single-dose of adrecizumab versus placebo in acute cardiogenic shock (ACCOST-HH): an investigator-initiated, randomised, double-blinded, placebo-controlled, multicentre trial. (PubMed, Lancet Respir Med) - P2/3 | "Adrecizumab was well tolerated in patients with cardiogenic shock but did not reduce the need for cardiovascular organ support or improve survival at days 30 and 90."

Clinical • Journal • Cardiovascular • Myocardial Infarction • Ventricular Tachycardia • ADM

AGNES-19: Adrecizumab (HAM8101) to Improve Prognosis and Outcomes in COVID-19 Trial (clinicaltrials.gov) - P2/3; N=218; Not yet recruiting; Sponsor: Universitätsklinikum Hamburg-Eppendorf

Biomarker • Clinical • New P2/3 trial • Infectious Disease • Novel Coronavirus Disease

European Society of Cardiology (ESC) Congress 2021 (August 27-30, 2021 - Virtual Meeting). (PubMed, Drugs Today (Barc)) - "The 2021 Congress of the European Society of Cardiology (ESC) was again held as a digital experience, providing poster and oral sessions highlighting the latest developments in cardiovascular science, including therapeutics for a range of related conditions and updates on ongoing trials, as well as guideline updates."

Journal • Cardiovascular

ACCOST-HH: Adrecizumab in Cardiogenic Shock (clinicaltrials.gov) - P2/3; N=150; Completed; Sponsor: Dr. med. Mahir Karakas; Recruiting ➔ Completed; Trial completion date: Jun 2020 ➔ Apr 2021; Trial primary completion date: Mar 2020 ➔ Apr 2021

Clinical • Trial completion • Trial completion date • Trial primary completion date

Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. (PubMed, Intensive Care Med) - "Overall, we successfully completed a randomized trial evaluating selecting patients for enrolment who had a disease-related biomarker. There were no overt signals of harm with using two doses of the adrenomedullin antibody adrecizumab; however, further randomized controlled trials are required to confirm efficacy and safety of this agent in septic shock patients."

Biomarker • Clinical • Journal • P2a data • Infectious Disease • Septic Shock • ADM

[VIRTUAL] ACCOST-HH: Adrecizumab in cardiogenic shock (ESC 2021) - No abstract available

Late-breaking abstract • Cardiovascular

Significance of adrenomedullin and the role of adrecizumab in sepsis. (PubMed, Saudi J Anaesth) - No abstract available

Journal • Infectious Disease • Septic Shock • ADM

AdrenOSS-2: Treatment of Patients With Early Septic Shock and Bio-Adrenomedullin(ADM) Concentration > 70 pg/ml With ADRECIZUMAB (clinicaltrials.gov) - P2; N=300; Recruiting; Sponsor: Adrenomed AG; Not yet recruiting ➔ Recruiting; Initiation date: May 2017 ➔ Dec 2017; Trial primary completion date: Dec 2018 ➔ Jul 2019

Clinical • Enrollment open • Trial initiation date • Trial primary completion date • Septic Shock • IL6

AdrenOSS-2: Treatment of Patients With Early Septic Shock and Bio-Adrenomedullin(ADM) Concentration > 70 pg/ml With ADRECIZUMAB (clinicaltrials.gov) - P2; N=300; Not yet recruiting; Sponsor: Adrenomed AG

Clinical • New P2 trial • Septic Shock • IL6