AM-Pharma Completes Phase 2 Enrollment for Ilofotase Alfa in Cardiac Surgery-Associated Kidney Injury Prevention
Key Insights
AM-Pharma (search) has completed enrollment of 244 patients in a Phase 2 trial evaluating ilofotase alfa for preventing cardiac surgery-associated renal damage (search), which affects up to 40% of cardiac surgery patients.
The multicenter, randomized, placebo-controlled study administered 128 mg ilofotase alfa intravenously before and after surgery, with topline results expected in early 2026.
Ilofotase alfa is a recombinant alkaline phosphatase that has demonstrated reno-protective effects in over 1,000 patients across clinical trials, potentially becoming the first approved therapy for this indication.
AM-Pharma (search) B.V. has successfully completed patient enrollment in its Phase 2 clinical trial evaluating ilofotase alfa for the prevention of cardiac surgery-associated renal damage (search) (CSA-RD), marking a significant milestone in addressing a serious post-surgical complication that affects up to 40% of cardiac surgery patients.
The multicenter, multinational, randomized, double-blind, placebo-controlled study (NCT06168799) enrolled 244 patients at high risk for renal damage following open-heart surgery. Patients received two intravenous doses of either 128 mg ilofotase alfa or placebo—one before and one after surgery—and are being followed for 60 days to assess efficacy, safety, and pharmacokinetics.
Addressing a Critical Unmet Medical Need
CSA-RD represents a serious complication arising from acute kidney injury (search) (AKI) following open heart surgery performed with cardiopulmonary bypass pumps. Apart from sepsis, this type of surgery is the most frequent cause of AKI, occurring in approximately one in three patients undergoing the surgical procedure.
"CSA-RD represents a serious post-surgical complication, often leading to prolonged hospitalization, increased complications such as the need for renal replacement therapy and a higher long-term risk of chronic kidney disease (search), end stage renal disease, and mortality," said Peter Pickkers, MD, PhD, Principal Investigator in the Phase 2 study and Professor of Experimental Intensive Care Medicine at Radboud University Nijmegen Medical Centre, The Netherlands.
Currently, no pharmacological therapies are available to prevent AKI, and the kidney injury can result in long-term renal impairment as well as the need for renal replacement therapy such as dialysis. Mortality rates can reach up to 50% in CSA-AKI patients who require renal replacement therapy post-operatively.
Study Design and Endpoints
The trial's primary endpoint is serum creatinine ratio (sCrR), a sensitive measure of kidney function changes that closely correlates with Major Adverse Kidney Events at 60 days (MAKE60). MAKE60, measured as a secondary endpoint in this study, is an FDA-registrable endpoint that would serve as the primary endpoint in the expected pivotal Phase 3 trial for ilofotase alfa.
Topline data, including MAKE60 results, are expected in early 2026, with the full dataset to be presented at a scientific conference thereafter.
Mechanism of Action and Clinical Experience
Ilofotase alfa is a recombinant alkaline phosphatase engineered from two human isoforms of the enzyme, demonstrating high activity and stability in multiple clinical trials. The recombinant enzyme works by dephosphorylating and detoxifying damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs)—including lipopolysaccharide (LPS), ATP, ADP, and other extracellular substrates—that drive acute inflammation, coagulation, and microvascular ischemia in the kidney following sepsis or ischemia-induced injury.
The dephosphorylation of ATP by ilofotase alfa provides dual reno-protective benefits: clearance of pro-inflammatory ATP and generation of adenosine, which activates the tissue-protective adenosine A2a receptor (search) pathway. Through this mechanism, ilofotase alfa has consistently demonstrated safety, tolerability, and reno-protective effects, including a reduction in Major Adverse Kidney Events (MAKE), across clinical studies in patients with sepsis associated-acute kidney injury (search) (SA-AKI), with an even greater effect observed in patients with pre-existing chronic kidney disease (search) (CKD).
The therapeutic candidate has been evaluated in more than 1,000 patients diagnosed with AKI across global clinical trials, establishing a proven safety profile and demonstrated kidney benefit. The drug has been granted FDA fast-track status for AKI treatment.
Broader Development Program
AM-Pharma (search) is developing ilofotase alfa as two distinct therapeutic products: an intravenous formulation for AKI and a highly concentrated subcutaneous formulation designed for chronic dosing as enzyme replacement therapy in hypophosphatasia (search) (HPP). The HPP indication has received orphan drug status in both the US and EU.
A Phase 1b study in adult HPP patients has reinforced the therapeutic potential of the subcutaneous formulation by demonstrating dose-dependent, clinically meaningful effects on key biomarkers (PPi, PLP, and PEA) and showing benefits beyond bone health, including improvements in muscle metabolism and stamina.
"Reaching this enrollment milestone is a key inflection point in the clinical development of ilofotase alfa, bringing us closer to addressing a significant unmet need in hospital care," said Juliane Bernholz, PhD, Chief Executive Officer of AM-Pharma (search). "With recruitment now complete, we are focused on the data that will inform our next steps to realize the potential for ilofotase alfa to become the first approved therapy to prevent CSA-RD."