Sepsis-associated acute kidney injury
Our goal is to develop and commercialize our proprietary recombinant human alkaline phosphatase therapeutic to transform the treatment prospects for patients with Sepsis-Associated Acute Kidney Injury (SA-AKI) – a devastating disease with high mortality rates and no approved pharmacological treatments, affecting millions of patients worldwide.
Urgent medical need
Acute kidney injury (AKI) is an acute inflammation of the kidney, which impairs the kidney function. It involves inflammatory processes in the kidney which may result in the need for dialysis. If the patient survives, the damage may not always be reversible and can even lead to complete loss of renal function, requiring kidney replacement. Hospital‐acquired AKI affects annually around 3 million patients in Europe, the US and Japan, and is associated with mortality in roughly 700,000 patients. It occurs in 40-60% of critical care admissions. Depending on the severity and cause of renal injury, mortality ranges from 10% to as high as 60%. In the US alone, hospitals spend around $10 billion each year on managing this major medical problem. The most important causes of AKI are sepsis, cardiovascular surgery, exposure to nephrotoxic drugs and trauma.
Patients with AKI have reduced alkaline phosphatase levels and activity in the kidneys. Alkaline phosphatase is a common endogenous enzyme present in many cells and organs (e.g. intestines, placenta, liver, bone, kidney and granulocytes). AM-Pharma has developed a novel recombinant human alkaline phosphatase as a medicinal product to be used via intravenous injection for the treatment of sepsis-associated acute kidney injury (SA-AKI). The recombinant alkaline phosphatase is an optimized recombinant human alkaline phosphatase with high stability and high activity.
AM-Pharma has shown that a short-term treatment with recombinant alkaline phosphatase helps protect kidney function in AKI, which can be classified as a disease modifying anti-inflammatory effect. Currently the only treatment option is dialysis and supportive care and no drugs are approved to treat AKI. Typically, these patients are treated in Intensive Care Units, often with support of nephrologists.
With no drugs currently approved to treat the condition, recombinant alkaline phosphatase could become the first pharmacological treatment for critically ill AKI patients.
Clinical Studies
Phase III Study update
We are conducting our Phase III REVIVAL pivotal study, a randomized, double-blind, placebo-controlled, two-arm, parallel-group, multi-center trial to evaluate the efficacy and safety of our proprietary human recombinant alkaline phosphatase for the treatment of patients with SA-AKI. The study will enroll approximately 1400 patients with SA-AKI in the main study population. In two exploratory cohorts, up to 100 patients with moderate Chronic Kidney Disease (CDK) and up to 100 patients with COVID-19 will be enrolled. The primary aim of the study is to confirm the improvement on the primary endpoint of 28-day all-cause mortality, as observed in the Phase II STOP-AKI study. Secondary endpoints include the treatment effect on long-term Major Adverse Kidney Events (MAKE), on the use of organ support, length of stay in the ICU and on 90-day all-cause mortality. Further information on this study can be found at www.clinicaltrials.gov, NCT04411472 (REVIVAL).
