12 November 2020
AM-Pharma Announces Enrollment of the First Patient in REVIVAL Phase III Pivotal Trial in Patients with Sepsis-Associated Acute Kidney Injury
Trial to confirm potential of AM-Pharma’s recombinant alkaline phosphatase to reduce mortality, as demonstrated in the Phase II STOP-AKI study
Target enrolment of up to 1,600 SA-AKI patients at ICUs in Europe, United Kingdom and North America
Utrecht, The Netherlands, 12 November 2020 – AM-Pharma B.V., an emerging leader focused on the treatment of kidney disease, sepsis and organ injury, today announced that it has enrolled the first patient in its global Phase III trial named REVIVAL (REcombinant human alkaline phosphatase SA-AKI surVIVAL trial). The REVIVAL trial will evaluate the Company’s proprietary recombinant alkaline phosphatase for the treatment of SA-AKI patients with the primary objective to confirm the reduction in mortality as demonstrated in the Company’s Phase II STOP-AKI trial1. Clinical trial sites across Europe, the United Kingdom and North America will enroll up to 1,600 SA-AKI patients.
“Sepsis-associated acute kidney injury is the cause of death for hundreds of thousands of people hospitalized each year. Currently, there are no treatments available outside of supportive care in an ICU,” stated Erik van den Berg, Chief Executive Officer at AM-Pharma. “Our compound represents an opportunity to reduce the high mortality rates and protect kidney function for patients with SA-AKI. Over the last 18 months, our focus has been to prepare a rigorous pivotal trial together with global AKI and sepsis experts, building on the strong Phase II STOP-AKI data and constructive interactions with the FDA and EMA. I would like to thank the AM-Pharma team, the clinical centers and the trial investigators for all their hard work and collaboration to achieve this important milestone today.”
The REVIVAL Phase III pivotal trial is a randomized, double-blind, placebo-controlled, two-arm, parallel-group, multi-center trial to evaluate the efficacy and safety of AM-Pharma’s proprietary human recombinant alkaline phosphatase for the treatment of patients with SA-AKI. The study will enroll approximately 1,400 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), organ support use, length of stay in the ICU and 90-day all-cause mortality. Further information on this study can be found at www.clinicaltrials.gov, NCT04411472 (REVIVAL).
“From the exciting results we have seen in the Phase II STOP-AKI trial, AM-Pharma’s drug candidate has the potential to transform the treatment landscape for patients with sepsis-associated acute kidney injury,” stated Professor Peter Pickkers, M.D., Ph.D., Chair of Experimental Intensive Care Medicine, Radboud University Medical Center, and principal investigator of the REVIVAL study. “In the Phase II STOP-AKI trial, treatment with AM-Pharma’s recombinant alkaline phosphatase resulted in a relative reduction in mortality of more than 40% and sustained improvement in renal function over the course of the 28-day study period. Based on these promising results, we are excited to be part of this pivotal study and the innovation we believe it can bring to SA-AKI treatment.”
“Sepsis is a highly prevalent, severe condition that causes long-term physical impact on patients who survive their admission to the ICU. The fact that there are currently no approved treatments available underscores the high unmet medical need for patients. We look forward to working together with AM-Pharma to potentially bring this treatment option to patients,” added John A. Kellum, M.D., Professor, Vice Chair Department of Critical Care Medicine and Director at the Center for Critical Care Nephrology at University of Pittsburgh.
For the Phase III REVIVAL trial, potentially over 100 sites across Europe, the United Kingdom and North America are actively recruiting patients with SA-AKI in the trial. Clinical site activation is progressing as planned and topline safety and futility analyses on the first 400 patients in the main study population is expected by the end of 2021. The Company expects to complete target enrollment and to announce data on the primary endpoint of 28-day all-cause mortality in 2023.
About AKI and Sepsis
Acute Kidney Injury (AKI) involves inflammatory processes in the kidney which can lead to complete loss of renal function. 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.2,3,4
Sepsis is a condition that is responsible for 1 out of 3 deaths in hospitals and is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The kidney is the most commonly affected organ, resulting in SA-AKI and significantly increasing the risk for mortality and morbidity in sepsis. No singular effective therapy to alter the progression of these devastating conditions has been approved, while the healthcare burden for sepsis in the US alone is $16.7 billion on an annual basis.5
About recombinant alkaline phosphatase
AM-Pharma’s therapeutic candidate is a proprietary recombinant human Alkaline Phosphatase (AP) constructed from two naturally occurring human isoforms of the AP enzyme. The Company’s compound is highly stable and active and has a dual mechanism of action via dephosphorylation of lipopolysaccharides (LPS) and extracellular ATP. AM-Pharma has shown that treatment of patients with exogenous AP not only reduces local and systemic inflammation but also protects the kidney against further damage.
AM-Pharma’s purpose is to save and improve the lives of patients confronted with kidney disease, sepsis and organ injury. Our initial focus is sepsis-associated acute kidney injury, the cause of death for hundreds of thousands of people hospitalized each year. Our proprietary recombinant human alkaline phosphatase has the potential to become the first treatment for sepsis-associated acute kidney injury and is now in a global pivotal Phase III clinical trial. We are a dedicated team driven to bring treatment options to severely ill patients, their families and acute care professionals.
Find out more about us online at: www.am-pharma.com.
1 Pickkers, P. et al. JAMA,2018; 320(19): 1998-2009
2 Murugan R. and Kellum J.A. Nature Reviews Nephrology, 2011; 7(4): 209-217
3 Heung M. and Chawla L.S. Nephron Clinical Practice, 2014; 127 (1-4): 30-34
4 Chertow, G.M. et al. Journal of the American Society of Nephrology, 2005; 16(11): 3365-3370 5 Alobaidi, R. et al. Seminars in Nephrology, 2015; 35(1): 2-11