Medical leaders support novel theragnostic approach to help patients with leaky blood vessels
HENNIGSDORF, Germany 05. January 2018 — Disorders caused by a leaky vasculature are more common than most people think. Despite ICU treatment, one third of the 27 million patients globally that suffer from sepsis, and up to 20% of the more than 5 million US patients with congestive heart failure die every year from their condition. Other disorders that involve a disturbed barrier function of the endothel , the innermost cell layer of blood vessels, include diabetes, migraine or inflammatory diseases. Medical opinion leaders have now confirmed evidence that adrenomedullin, a central regulator of endothelial function, could serve both as a diagnostic biomarker and a therapeutic target in disorders caused by endothelial dysfunction.
Until now, physicians had no means to identify patients with bad sepsis prognosis and those heart failure patients with congestion who relapse due to residual disease at discharge. International medical leaders have now compiled clinical data from more than 10,000 patients suffering from sepsis and congestive heart failure, whose survival was linked to blood levels of the peptide hormone adrenomedullin. Results presented in Berlin identify the active form of adrenomedullin, dubbed bio-ADM, as a biomarker that predicts development of septic shock and for the first time allows doctors to identify heart failure patients, who will relapse despite decongestive treatment with loop diurectics. While sepsis supportive treatment causes annual healthcare cost of nearly $24bn, congestive heart failure treatment and rehospitalisation costs due to unidentified residual disease totaled at $31bn in the US alone. The latter annual cost is expected to double by 2030.
A diagnostic test for bio-ADM , developed and marketed by diagnostics company Sphingotec in Europe and China, is already in place. An adrenomedullin-specific therapeutic antibody, developed by Berlin-based Adrenomed AG, has just entered proof-of-concept studies in septic shock patients; a Phase II study in patients with decompensated heart failure is expected to start in 2018. According to serial entrepreneur Andreas Bergmann, founder of both companies and co-founder of BRAHMS (taken over in 2009), “bio-ADM is a general indicator for endothelial dysfunction and the need of vascular repair.”
Clinical data from more than 4,000 Caucasian and Asian sepsis patients presented at the scientific symposium “Endothelial dysfunction – Adrenomedullin as a diagnostic and therapeutic target” demonstrate that low bio-ADM plasma levels (<70pg/mg) at baseline were linked to a good outcome. In contrast, bio-ADM levels above that cut-off value were linked to significantly higher mortality (up to 13-fold), organ dysfunction and high vasopressor demand. As bio-ADM levels rose 24+ hours before septic shock occurred it allowed both early intervention and therapy monitoring. bio-ADM indicated endothelial integrity in sepsis patients at emergency departments, ICUs and patients with surgical sepsis.
Further clinical data from more than 6,000 patients with acute and chronic heart failure suffering from congestion and edema caused by high venous pressure and vascular fluid leakage, demonstrate that high bio-ADM levels predicted residual congestion, rehospitalisation and 180-day mortality. Measuring bio-ADM levels is the very first method that allows identification of patients with acute heart failure that have residual congestion and mustn’t be discharged in order to prevent rehospitalisation and death.
Using adrenomedullin as a therapeutic target seems to be a next logical step.
Preclinically, Adrecizumab, a humanized antibody that binds adrenomedullin without affecting its receptor binding in the endothel, led to a 40% survival benefit in mice. In two Phase I trials the first-in-class antibody showed excellent safety and tolerability in sepsis patients. Pharmakokinetic and pharmacodynamic data suggest that antibody stabilizes adrenomedullin’s half-life from 22 minutes to several days and that antibody binding leads to a redistribution from the vessel interstitium to its lumen, where is closes in gaps in the endothelium and thus restores the blood vessels barrier function. A Phase II trail on 300 patients with early septic shock is underway, while a Phase II study in congestive heart failure patients is in preparation and is expected to start in 2018.
About the speakers at the scientific symposium
- Prof. Dr. Inder Anand, Department of Cardiovascular Medicine, University of Minnesota Medical School,
- VA Medical Center Minneapolis MN and San Diego, USA
- Prof. Dr. Aw Tar Choon, Changi General Hospital, Singapore
- Prof. Dr. Javed Butler, Chief of the Cardiology Divisionat Stony Brook School of Medicine, USA
- Prof. Dr Salvatore Di Somma, Director Emergency Medicine, University La Sapienza, Rome, Italy
- Asj-Prof. Dr. Hans-Dirk Düngen, Head Multicentric Studies Cardiology, Charité Berlin, Germany
- Prof. Dr. Mina Hur, Director Department of Laboratory Medicine, Konkuk University Seoul, Korea
- Prof. Dr Pierre-Francois Laterre, Head of the medical-surgical intensive care unit at St. Luc Hospital, Brussels, Belgium
- Dr. Roberto Latini, Istituto di Ricerche Farmacologiche Mario Negri Milano, Italy
- Prof. Dr. Gernot Marx, Director Operative Intensive Care and Intermediate Care, University Clinic Aachen, Germany
- Prof. Alexandre Mebazaa, Head AP-HP, Hôpital Lariboisière Paris, France
- Prof. Dr. Olle Melander, Principal investigator at Hypertension and Cardiovascular Disease, Lund University Malmö, Sweden
- Prof. Dr. Marco Metra, Department of Medical and Surgical Specialties. Universita degli Studi di Brescia, Italy
- Prof. Leong L. Ng, Principal Investigator, Department of Cardiovascular Sciences, University Leicester, UK
- Prof. Dr. Peter Pickkers, Department of Intensive Care. Radboud University, Nijmegen, The Netherlands
- Prof. Adriaan A. Voors, Director of the Heart Failure Clinic and the Outpatient Clinic of the.Department of Cardiology, UMC Groningen, The Netherlands
About congestive heart failure:
About 5 million US-Americans suffer from congestive heart failure. The characteristic loss of pump function of the heart triggers cardiac remodeling – the heart gets stiffer, fibrotic, and cannot pump enough blood into the circulatory system. The lower pump efficacy causes lower oxygen saturation and results in congestion, which means that blood returning to the heart through the veins backs up, resulting in higher venous pressure and causing fluids to build up in the tissues (edema). About 80% of patients with congestive heart failure are also at risk to develop edema, because their microvasculature becomes leaky due to venous hypertension. Physicians try to prevent the worst case – deadly lung edemas – by administration of loop diuretics, which can reduce hypertension by increasing water excretion. However, not all patients fully respond to diuretics. Incomplete response to diuretics therapy is the most common cause of re-hospitalization and post discharge mortality in patients with congestive heart failure. It’s not yet fully understood why patients with congestive heart failure often experience acute kidney injury (AKI). However, there is growing evidence that AKI can be attributed to congestion („cardio-renal syndrome“) and that, vice versa, AKI can trigger heart problems. Management of fluid balance with loop diuretics is challenging – if too much fluid is excreted from tissues, this will support development of AKI. On the other hand, if too little fluid is excreted, lung edemas could return. Besides that, a large proportion of patients with congestive heart failure does not fully respond to diuretics treatment, leading to undetected residual congestion. To date, physicians have no means to identify these patient group at discharge, resulting in high re-hospitalization and post-discharge mortality rates.
About septic shock
Septic shock is defined as a life-threatening organ dysfunction due to dysregulated host response to a proven or suspected infection which leads to a decline of Mean Arterial Pressure (MAP) < 65 mmHg, which is refractory to fluid resuscitation and requires vasopressors. Refractoriness to fluid resuscitation is defined as a lack of response to the administration of 30 mL of fluid per kilogram of body weight or is determined according to a clinician’s assessment of inadequate hemodynamic results
About Adrenomedullin
Adrenomedullin is a strong vaso-regulatory hormone released by smooth muscle cells and the endothelium. It is a key regulator of blood pressure and vascular tone and plays a pivotal role in the regulation of the endothelial barrier function.
About Adrecizumab
Adrecizumab is a proprietary humanized monoclonal Adrenomedullin-specific antibody, as first-in-class therapy for the treatment and prevention of impaired vascular integrity, which is a hallmark of septic shock. Adrecizumab showed excellent safety & tolerability as well as high efficacy in a variety of preclinical animal models, mimicking human standard of care treatment on ICU. In several resuscitated vascular integrity models (mouse, rat, pig), Adrecizumab reduced vascular leakage, stabilized the circulation, by restoring blood pressure, normalized fluid balance and reduced vasopressor demand, improved renal function and reduced mortality from septic shock by 50%. The excellent tolerability and safety of Adrecizumab was confirmed in two clinical Phase-I studies in healthy subjects with and without LPS challenge.
About SphingoTec GmbH:
SphingoTec GmbH (Hennigsdorf, Germany) develops innovative biomarkers for prediction, diagnosis and therapy monitoring of AKI, congestive heart failure and septic shock. The company, founded by Dr. Andreas Bergmann in 2002, has also in its portfolio biomarkers which can predicts risks of obesity, breast cancer and cardiovascular diseases.
About Adrenomed
Adrenomed AG is a privately financed biopharmaceutical company, based in Hennigsdorf near Berlin, Germany, with the mission to improve survival by improving vascular integrity in critically ill patients. Its lead candidate, Adrecizumab, a monoclonal antibody therapy targeting the vasoactive adrenomedullin system, is in clinical testing for early septic shock. Impaired vascular integrity is a pathology observed in a variety of medical conditions. A further indication besides sepsis and early septic shock is acute decompensated heart failure.
• PenKid surpasses serum creatinine on Day 1 post-transplant in detecting delayed graft function (DGF), with an AUROC of 0.87 versus 0.56 for creatinine. • PenKid differentiates slow graft function (SGF) from DGF up to 8 days earlier than current methods, supporting more timely clinical decisions. • PenKid levels remain unaffected by kidney replacement therapy (KRT), allowing for more accurate assessment of kidney function. • Independent validation in transplant cohort from Australia confirms performance and broad applicability. Hennigsdorf/Berlin, Germany, July 1, 2025 - Diagnostic company SphingoTec GmbH (“SphingoTec”) announces a landmark study (1) published in Transplant International, led by Heidelberg University Hospital in Germany in collaboration with researchers from Sydney, Australia, which identifies Proenkephalin A 119-159 (penKid) as a reliable biomarker for early and precise assessment of graft function trajectories following kidney transplantation. The research demonstrates that PenKid not only identifies patients at risk for DGF significantly earlier than traditional markers but also distinguishes between slow and delayed graft function with remarkable accuracy, offering clinicians a valuable new tool for patient management. The study prospectively evaluated 159 consecutive kidney transplant recipients at Heidelberg University Hospital and validated findings in an independent cohort from Sydney. PenKid consistently outperformed serum creatinine (SCr) in predicting graft function trajectories, particularly in the critical early post-transplant period. Notably, PenKid’s ability to remain unaffected by KRT—a treatment for severe kidney dysfunction—further sets it apart from SCr, which can be influenced by non-renal factors and KRT itself, thereby enhancing the reliability of graft function assessment. Multivariate analysis confirmed PenKid as the strongest independent predictor of both short-term graft function and 30-day outcomes, underscoring its clinical utility for early risk stratification. The biomarker’s superior granularity allows for nuanced classification of DGF severity, supporting more informed decisions regarding the initiation of dialysis or biopsy and offering potential for individualized patient care. With these findings, penKid steps forward as a practical addition to the transplant clinician’s toolkit, promising to sharpen decision-making for optimal outcomes. Its adoption could help transplant teams act with greater confidence and precision, ultimately strengthening the standard of care in kidney transplantation. ## References 1. Benning L et al. (2025) Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories. Transpl. Int. 38:14366. doi: 10.3389/ti.2025.14366 About SphingoTec SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) is a biomarker company focusing on the out-licensing of innovative critical care solutions for diagnosing, predicting, and monitoring acute medical conditions. SphingoTec develops its biomarkers to the commercial stage and partners with IVD companies to make them available on different IVD platforms. SphingoTec's proprietary biomarker portfolio includes Proenkephalin A 119-159 (penKid), a biomarker for the assessment of kidney function in critical diseases, commercially available on diagnostic platforms AFIAS and Nexus IB10 and bioactive Adrenomedullin 1-52 (bio-ADM), a biomarker for the assessment of endothelial function in conditions like sepsis. Discover more on www.sphingotec.com Contact : Ruxandra Lenz Marketing and Communication SphingoTec GmbH Phone +49-3302-20565-0 Email: press@sphingotec.com
• Boditech Med and SphingoTec announce the launch of the AFIAS sphingotest® penKid® assay, a diagnostic tool designed to aid in kidney function assessment for critically ill patients. • The IVDR-marked assay provides quantitative measurements of Proenkephalin A 119-159 (penKid), supporting clinical decision-making in acute and critical care. • This launch follows a licensing agreement granting Boditech the rights to develop and commercialize penKid-based assays, as well as a market development agreement between the two companies. Gangwon-do, Republic of Korea, and Hennigsdorf/Berlin, Germany, May 6, 2025 - Boditech Med Inc. (“Boditech”) and SphingoTec GmbH (“SphingoTec”) today announced the commercial launch of the AFIAS sphingotest® penKid® assay. The assay is designed to provide clinicians with a tool for assessing kidney function in critically ill patients by measuring Proenkephalin A 119-159 (penKid), a biomarker that reflects real-time kidney function independently of inflammation or comorbidities. The AFIAS sphingotest® penKid® assay is IVDR-marked for its intended use as an automated fluorescence immunoassay for the in vitro diagnostic quantitative determination of Proenkephalin A 119-159 in human whole blood/plasma, serving as an aid in the diagnosis of acute kidney injury (AKI) in adult patients with sepsis or septic shock. It provides additional information to support clinical decision-making in managing critically ill patients at risk of acute kidney injury (AKI). This launch is the result of a strategic collaboration between Boditech and SphingoTec, including a licensing agreement granting Boditech the rights to develop and commercialize penKid-based assays on its diagnostic platforms, as well as a market development agreement aimed at accelerating global commercialization efforts. Eui-Yul Choi, CEO of Boditech Med, commented: “We are proud to introduce the AFIAS sphingotest® penKid® assay to clinicians worldwide. This launch reflects our commitment to delivering innovative diagnostic solutions that address critical needs in healthcare. Our collaboration with SphingoTec has been instrumental in bringing this important tool to market.” Deborah Bergmann, CEO of SphingoTec, added: “The launch of AFIAS sphingotest® penKid® demonstrates how partnerships can drive innovation and improve access to advanced diagnostics. By combining our biomarker expertise with Boditech’s diagnostic capabilities, we are reaching a new chapter in our collaboration. We are streamlining our processes to support the business of our license partners and further expand our global reach. This enables us to provide clinicians with essential tools to enhance patient care.” Scientific insights on penKid PenKid is a biomarker that enables real-time assessment of kidney function (1). Unlike traditional markers such as serum creatinine, penKid levels are not influenced by inflammation or other confounding factors like age or sex (1,2,3). Studies have shown that penKid allows earlier detection of acute kidney injury (AKI), predicting changes in serum creatinine up to 48 hours before conventional diagnostic criteria are met (1,3). This early detection capability is particularly valuable in critically ill patients, including those with sepsis or septic shock (1,3,4). Additionally, penKid has shown potential for monitoring renal recovery under dialysis and could help predict successful weaning from renal replacement therapy (5,6). ## References 1. Hollinger A, et.al. Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study. Kidney Int Rep. 2018 Aug 22;3(6):1424-1433. doi: 10.1016/j.ekir.2018.08.006. 2. Beunders et al. Assessing GFR With Proenkephalin, Kidney International Reports, 2023, DOI: https://doi.org/10.1016/j.ekir.2023.08.006 3. Caironi et al., Circulating proenkephalin, acute kidney injury, and its improvement in patients with severe sepsis or shock. Clin Chem (2018) DOI:10.1373/clinchem.2018.288068 4. Moledina DG. Penkid: A Novel Biomarker of Reduced GFR in Sepsis. Kidney Int Rep. 2018 Nov 15;4(1):17-19. doi: 10.1016/j.ekir.2018.11.002. 5. von Groote T et al. Proenkephalin A 119–159 predicts early and successful liberation from renal replacement therapy in critically ill patients with acute kidney injury: a post hoc analysis of the ELAIN trial. Crit Care 26, 333 (2022). doi.org/10.1186/s13054-022-04217-4 6. von Groote T, et al. Evaluation of Proenkephalin A 119-159 for liberation from renal replacement therapy: an external, multicenter pilot study in critically ill patients with acute kidney injury. Crit Care. 2023 Jul 10;27(1):276. doi: 10.1186/s13054-023-04556-w. About Boditech Boditech Med (based in Chuncheon, Gangwon-do, Republic of Korea) is a leading company in the field of point-of-care diagnostics, which has accumulated 25 years of business expertise in the field. The company has more than 80 types of in vitro diagnostic products that detect biomarkers related to infectious diseases, diabetes, cardiovascular diseases, cancer, and hormone-related diseases with its immunofluorescence lateral flow technology, quantitative immunofluorescence technology and spectrophotometric technology. And the list continues to grow with new high-value-added products. With its instrument platform installed in more than 120 countries, the company also has a stable revenue model. The company is currently strengthening its value as a global company by expanding its manufacturing bases in the US, China, India, and Indonesia. About SphingoTec SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) is a diagnostic company focusing on the out-licensing of innovative critical care biomarkers for diagnosing, predicting, and monitoring acute medical conditions. SphingoTec develops its biomarkers to the commercial stage and partners with IVD companies to make them available on different IVD platforms. SphingoTec's proprietary biomarker portfolio includes Proenkephalin A 119-159 (penKid), a biomarker for the assessment of kidney function in critical diseases, commercially available on diagnostic platforms AFIAS and Nexus IB10 and bioactive Adrenomedullin 1-52 (bio-ADM), a biomarker for the assessment of endothelial function in conditions like sepsis. Discover more on www.sphingotec.com Contact: Ruxandra Lenz Head of Marketing and Communication SphingoTec GmbH Phone +49-3302-20565-0 Email: press@sphingotec.com