AM-Pharma Enrolls First Patient in Japan for Ongoing Phase III SA-AKI Pivotal REVIVAL Trial

UTRECHT, The Netherlands--(BUSINESS WIRE)--AM-Pharma B.V., an emerging leader focused on developing therapeutics for severe medical conditions, today announced the enrollment of the first patient in Japan as part of its ongoing global pivotal Phase III trial, called REVIVAL. The REVIVAL study is evaluating ilofotase alfa, the Company’s proprietary recombinant human alkaline phosphatase, for the treatment of sepsis-associated acute kidney injury (SA-AKI) in up to 1,600 patients in North America, Europe and Japan. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) recently approved the start of patient enrollment into the REVIVAL trial in Japan.

“The approval of the Clinical Trial Notification (CTN) for our REVIVAL study by the PMDA followed by the treatment of the first patient with SA-AKI in Japan is a major achievement for AM-Pharma, as it demonstrates our ability to conduct a pivotal study on a global scale and moves us a step closer to bringing ilofotase alfa to patients in need,” said Erik van den Berg, Chief Executive Officer at AM-Pharma. “SA-AKI is associated with mortality in hundreds of thousands of people hospitalized each year and ilofotase alfa is the most advanced disease-modifying treatment in development for this indication. We plan to work diligently to bring our innovative therapeutic candidate to patients worldwide.”

Dr. Kent Doi, Assistant Professor at The University of Tokyo, Trial Steering Committee Member and National Coordinator for REVIVAL in Japan commented: “There is a tremendous medical need in Japan and globally for treatment options for sepsis-associated acute kidney injury. We welcome the opportunity to be a part of the REVIVAL trial to evaluate AM-Pharma’s therapeutic candidate with the hope we can contribute to the development of a new drug to aid these patients, who have no real treatment option today other than supportive care.”

About REVIVAL

The REVIVAL trial is a Phase III pivotal study evaluating AM-Pharma’s proprietary recombinant alkaline phosphatase, ilofotase alfa, for the treatment of patients with SA-AKI. The primary endpoint of the study is all-cause mortality 28 days post-treatment start with ilofotase alfa at a dose of 1.6 mg/kg. In the Phase II study of ilofotase alfa, patients treated with this dose experienced a statistically significant 46% relative reduction in mortality compared to patients treated with placebo (p= 0.022). REVIVAL was initiated in November 2020 and is enrolling up to 1,600 patients in North America, Europe and Japan. As per the study protocol, four interim analyses for futility and/or efficacy will be conducted when enrollment hits certain levels and the first futility analysis will occur when 400 patients have been treated.

Up to about 120 clinical sites worldwide, including as many as 11 sites in Japan, will enroll patients into the single global pivotal Phase III REVIVAL trial in SA-AKI patients. The U.S. Food and Drug Administration, European Medicines Agency and Japanese Pharmaceuticals and Medical Devices Agency have all approved the REVIVAL protocol.

In addition to the REVIVAL study, the PMDA has approved enrollment into a Phase I pharmacokinetics (PK), safety and tolerability study in healthy Japanese subjects, which is being conducted in parallel to REVIVAL in Japan.

About ilofotase alfa

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. The recombinant enzyme displays exquisite activity towards dephosphorylating and detoxifying damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), ATP, ADP and other extracellular substrates that drive acute inflammation, coagulation and microvascular ischemia. Research has shown that ATP dephosphorylation has a double effect in protecting against kidney injury. When the pro-inflammatory ATP is dephosphorylated, the resulting adenosine further reduces inflammation through the activation of the immunosuppressive adenosine A2a receptor pathway (A2aR). AM-Pharma has shown that treatment of patients with ilofotase alfa not only reduces local and systemic inflammation but also protects the kidney against further damage.

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 the US, Europe, 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 occurs in up to 60% of the cases. In the US alone, hospitals spend around $10 billion each year on managing this major medical problem.^1,2,3

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.⁴

About AM-Pharma

AM-Pharma's purpose is to save and improve the lives of patients confronted with severe medical conditions. Our initial focus is sepsis-associated acute kidney injury, the cause of death for hundreds of thousands of people hospitalized each year. Our proprietary compound, ilofotase alfa, 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.

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¹ Murugan R. and Kellum J.A. Nature Reviews Nephrology, 2011; 7(4): 209-217

² Heung M. and Chawla L.S. Nephron Clinical Practice, 2014; 127 (1-4): 30-34

³ Chertow, G.M. et al. Journal of the American Society of Nephrology, 2005; 16(11): 3365-3370

⁴ Alobaidi, R. et al. Seminars in Nephrology, 2015; 35(1): 2-11