AM-Pharma Initiates Phase 2 Trial of Ilofotase Alfa for Cardiac Surgery-Associated Renal Damage

2024-01-16

临床2期快速通道孤儿药临床1期

Trial will evaluate ilofotase alfa as a treatment to prevent renal damage in at-risk patients following open heart surgery Ilofotase alfa’s clinical record of renal protective effects supports therapeutic potential in underserved and high-need indication UTRECHT, The Netherlands--(BUSINESS WIRE)-- AM-Pharma B.V. today announced that the first patients have been treated in a Phase 2 clinical study evaluating the company’s proprietary recombinant alkaline phosphatase, ilofotase alfa, as a preventive treatment for cardiac surgery-associated renal damage (CSA-RD). With over 2 million open heart surgeries1 performed worldwide every year, CSA-RD represents a critical surgical complication for which there is no specific pharmacological therapy. CSA-RD is defined as the long-term loss of renal function in cardiac surgery patients and arises from acute kidney injury (AKI) immediately following the surgery. CSA-AKI occurs in approximately 1 out of 3 patients undergoing open heart surgery and is the predominant risk factor for death post-surgery, with 2-5% of patients requiring renal replacement therapy as a result. Ilofotase alfa has a proven safety and tolerability pro a strong record of renal protective effects as observed in previous clinical studies. Notably, prior Phase 2 and Phase 3 trials with ilofotase alfa demonstrated significant improvements in Major Adverse Kidney Events by day 90 (MAKE90) in sepsis-associated AKI. As recently reported in a publication2 on the REVIVAL Phase 3 trial, MAKE90 events were reduced to 57.2% of patients in the ilofotase alfa group compared to 64.7% in the placebo group. “Previous clinical trials showed ilofotase alfa had significant reno-protective effects in sepsis-associated AKI patients. Given the role of AKI in long-term renal impairment in cardiac surgery patients, ilofotase alfa preventative treatment could have substantial clinical benefits on renal function and potentially save lives,” 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. The multicenter, double-blind, randomized, placebo-controlled Phase 2 trial will evaluate the efficacy and safety of ilofotase alfa as a preventive treatment in 150 patients scheduled for cardiac surgery and at risk for CSA-RD. Treatment will be administered intravenously before and after surgery, with a follow-up period of 60 days. The primary endpoint will be the ratio between pre- and post-surgery creatinine levels. Important exploratory endpoints will be the incidence of Major Adverse Kidney Events (MAKE) and the incidence and severity of AKI post-surgery. The trial is planned to end in Q4 2024 with a data readout expected in early 2025. Ilofotase alfa was recently evaluated in a Phase 1b pilot study as enzyme replacement therapy in hypophosphatasia (HPP) patients. “With the initiation of the Phase 2 trial in CSA-RD following the positive results from the Phase 1b study in HPP we have achieved important progress toward establishing ilofotase alfa’s potential through our updated clinical development strategy. We are confident in our new trajectory and remain committed to delivering a therapeutic solution for patients in these two severe, high-need conditions,” said Juliane Bernholz, PhD, Chief Executive Officer of AM-Pharma. “The clinical centers we are working with show great enthusiasm for our approach with ilofotase alfa and we look forward to the data readout.” About ilofotase alfa Ilofotase alfa is a proprietary recombinant alkaline phosphatase, constructed from two human isoforms of alkaline phosphatase, that has been shown to be stable and highly active in multiple clinical trials. 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 found in kidney following sepsis or ischemia-induced damage. 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. In hypophosphatasia, ilofotase alfa addresses elevated levels of pyridoxal-5′-phosphate (PLP), inorganic pyrophosphates (PPi), two disease-related biomarkers that are related to bone mineralization and pain sensation, for example. About cardiac surgery-associated renal damage (CSA-RD) CSA-RD is a clinical complication that arises from acute kidney injury (AKI) following open heart surgery performed with the use of a cardiopulmonary bypass (CPB) pump. Apart from sepsis, this type of surgery is the most frequent cause of AKI. CSA-AKI occurs in about 1 in 3 patients undergoing this surgical procedure.3 Pre-operative and intra-operative measures can be taken to reduce the risk of AKI, and post-operative management strategies may also help mitigate further damage.4 However, there is currently no pharmacological therapy to prevent AKI, and the kidney injury can result in long-term renal impairment and the need for renal replacement therapy (RRT) such as dialysis. Notably, mortality can be up to 50% in CSA-AKI patients who require RRT post-operatively. About AM-Pharma AM-Pharma strives to develop medicines for patients confronted with severe medical conditions. Our proprietary asset, ilofotase alfa, is being developed for the treatment of patients with acute kidney injury (AKI) and has been granted FDA fast-track status. We also develop ilofotase alfa in the severe rare disease hypophosphatasia where ilofotase alfa has orphan drug status in the US and EU. With approximately 1,000 subjects evaluated to date in clinical trials, ilofotase alfa has a proven safety pro a demonstrated kidney benefit. 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: . 1 2 Pickkers P et al., Intensive Care Med., 2024 3 Andújar A et al., Front. Nephrol., 2023 4 Ostermann M et al., J Clin Med., 2021 View source version on businesswire.com: Contacts Investors: Juliane Bernholz, Chief Executive Officer j.bernholz@am-pharma.com Media: Trophic Communications Gretchen Schweitzer or Priscillia Perrin +31 6 52 33 15 79 am-pharma@trophic.eu Source: AM-Pharma View this news release online at: