HENNIGSDORF and BERLIN, Germany—Adrenomed AG has reported positive top-line results from its proof-of-concept AdrenOSS-2 Phase 2 trial. The trial evaluated the safety, tolerability and efficacy of Adrecizumab, a first-in-class monoclonal antibody targeting the vasoprotective peptide Adrenomedullin to restore and maintain vascular integrity in patients with early septic shock.
“These are very promising results and consistent data,” said Dr. Jens Zimmermann, chief medical officer of Adrenomed. “The outcome of the AdrenOSS-2 trial indicates that Adrecizumab is of benefit for septic shock patients. By restoring and maintaining vascular integrity, Adrecizumab may represent a new treatment option for septic shock.”
Sepsis is a life threatening condition that results in organ dysfunction caused by a dysregulated host response to infection. Septic shock is the most severe form of sepsis, characterized by a rapid fall in blood pressure, requiring vasopressor treatment; profound circulatory, cellular and metabolic abnormalities; diminished oxygen supply to organs; and multiple organ failure.
Septic shock is driven by severe loss of vascular integrity: a breakdown of the endothelial barrier, which results in uncontrolled leakage of intravascular fluid and other compounds into the extravascular space, leading to congestion and edema. Today, sepsis and septic shock are major healthcare problems, representing a high unmet medical need affecting millions of people around the world every year.
“Safe and efficacious treatments are urgently needed to change the course of this complex condition. Undoubtedly, AdrenOSS-2 exhibited benefits on survival in septic shock patients, suggesting great potential for endothelial modulation on septic shock outcomes,” commented Prof. Alexandre Mebazaa, M.D., Ph.D., chair of the department of Anesthesiology and Critical Care in Paris at the Hôpital Lariboisière, Université de Paris.
Adrecizumab targets bioactive Adrenomedullin to restore endothelial barrier function, and thus improve vascular integrity. Binding the monoclonal Adrecizumab to Adrenomedullin in the blood traps and stabilizes the peptide-hormone, resulting in increased Adrenomedullin concentrations within the blood vessels.
“Endothelial dysfunction is the major driver for organ dysfunction and mortality in sepsis,” added Dr. Andreas Bergmann, chief scientific officer and co-founder of Adrenomed. “The biomarker [Adrenomedullin] specifically enables the identification of sepsis patients with endothelial dysfunction, who potentially may benefit the most from Adrecizumab treatment. Biomarker guidance of specific drugs will lead to new directions for fighting multi-complex diseases like sepsis.”
The biomarker-guided, randomized, double-blind, placebo-controlled AdrenOSS-2 Phase 2 trial enrolled a total of 301 patients with early septic shock and elevated blood levels of Adrenomedullin throughout Belgium, France, Germany and The Netherlands. In addition to standard of care, patients received Adrecizumab or placebo.
The study achieved its primary endpoint. The safety and tolerability of Adrecizumab in septic shock patients were consistent with observations from the previous Phase 1 trials. The mortality rate in the 28 day follow-up in the placebo group was 28%, and a trend of lower all-cause mortality for Adrecizumab-treated patients compared to placebo was observed.
“For the first time, we have seen a positive effect on early death in septic shock. The outcome of AdrenOSS-2 is an important step towards successful treatment of sepsis. The data support Adrecizumab being an effective therapeutic agent with an innovative mode of action which may improve survival of patients in the early stage of septic shock,” noted Prof. Pierre-François Laterre, M.D., head of the medical-surgical intensive care unit at Saint Luc University Hospital at the Université Catholique de Louvain in Brussels, Belgium. “We eagerly await the confirmation of these positive results in the future clinical development of Adrecizumab.”
“We are looking forward to further discussions with regulatory authorities and partners regarding the future development of Adrecizumab. With this successful proof-of-concept trial, we believe Adrecizumab has great potential not only in septic shock but also in other serious or life-threatening conditions associated with vascular leakage. We would like to take this opportunity to thank the investigators, study personnel, patients and their families for their participation in the AdrenOSS-2 trial,” concluded Dr. Jens Schneider-Mergener, chief executive officer of Adrenomed.
Detailed data from the AdrenOSS-2 study will be submitted for publication in a peer-reviewed journal later this year.