Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab (HAM8101)

Abstract

Recently, the stabilization of the endothelium has been explicitly identified as a therapeutic goal in coronavirus disease 2019 (COVID-19). Adrecizumab (HAM8101) is a first-in-class humanized monoclonal anti-Adrenomedullin (anti-ADM) antibody, targeting the sepsis- and inflammation-based vascular and capillary leakage. Within a “treatment on a named-patient basis” approach, Adrecizumab was administered to eight extreme-critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). The patients received a single dose of Adrecizumab, which was administered between 1 and 3 days after the initiation of mechanical ventilation. The SOFA (median 12.5) and SAPS-II (median 39) scores clearly documented the population at highest risk. Moreover, six of the patients suffered from acute renal failure, of whom five needed renal replacement therapy. The length of follow-up ranged between 13 and 27 days. Following the Adrecizumab administration, one patient in the low-dose group died at day 4 due to fulminant pulmonary embolism, while four were in stable condition, and three were discharged from the intensive care unit (ICU). Within 12 days, the SOFA score, as well as the disease severity score (range 0–16, mirroring critical resources in the ICU, with higher scores indicating more severe illness), decreased in five out of the seven surviving patients (in all high-dose patients). The PaO2/FiO2 increased within 12 days, while the inflammatory parameters C-reactive protein, procalcitonin, and interleukin-6 decreased. Importantly, the mortality was lower than expected and calculated by the SOFA score. In conclusion, in this preliminary uncontrolled case series of eight shock patients with life-threatening COVID-19 and ARDS, the administration of Adrecizumab was followed by a favorable outcome. Although the non-controlled design and the small sample size preclude any definitive statement about the potential efficacy of Adrecizumab in critically ill COVID-19 patients, the results of this case series are encouraging.

Patient Characteristics and Clinical Course of COVID-19 Patients Treated at a German Tertiary Center during the First and Second Waves in the Year 2020

“…A higher proportion of patients received antibiotic treatment during the first compared to the second wave (66% [ n = 114] vs. 45% [ n = 148]; p < 0.001). Hydroxychroloquin, lopinavir/ritonavir, tocilizumab [ 17 ], and the anti-adrenomedullin antibody adrecizumab [ 18 ] were only used during the first wave ( Supplementary Materials Figure S2 and Table S2 ). Convalescent plasma was administered to six patients (3%) during the first wave and eight patients (2%) during the second wave.…”

Comparison of clinical characteristics and disease outcome of COVID-19 and seasonal influenza

“…Patients who participated in placebo-controlled, double-blind treatment studies were assigned to the treatment group for this analysis. Immunotherapy was defined as administration of convalescent plasma, the anti-IL-6 antibody tocilizumab, or the anti-adrenomedullin antibody adrecizumab 29 , while administration of hydrocortisone as part of the treatment regimen for septic shock or the administration of other immunosuppressive agents for indications other than influenza and COVID-19 respectively during the hospitalization was omitted. Bacterial, viral, or fungal co-infections were assessed by chart review, and only isolates determined by the treating physician to be clinically significant were included in the analysis.…”

Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection

“…The anti-ADM antibody Adrecizumab stabilizes and maintains the endothelial barrier function and is thus supposed to reduce capillary leakage in septic shock, which is also described as a pathomechanism in COVID-19 [40,41]. In a small case series with eight critically ill COVID-19 patients, the administration of Adrecizumab seemed to favor the clinical outcome [42].…”