recombinant human alkaline phosphatase intravenous (recAP) / AM Pharma - LARVOL DELTA

Phenotype-specific therapeutic efficacy of ilofotase alfa in patients with sepsis-associated acute kidney injury. (PubMed, Crit Care) - "We identified a clinical phenotype comprising severely ill patients with underlying kidney disease who benefitted most from ilofotase alfa treatment. This yields insight into the therapeutic potential of this novel treatment in more homogeneous patient groups and could guide patient selection in future trials, showing promise for personalized medicine in SA-AKI and other complex conditions."

Journal • Acute Kidney Injury • Chronic Kidney Disease • Infectious Disease • Nephrology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Septic Shock

Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL). (PubMed, Intensive Care Med) - "Among critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified."

Journal • P3 data • Acute Kidney Injury • Chronic Kidney Disease • Critical care • Infectious Disease • Nephrology • Renal Disease • Septic Shock

Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: AM-Pharma | Recruiting ➔ Completed

Biomarker • Trial completion • ALPL

Decoding Survival: The Role of Bone Biomarkers in Hormone-Sensitive Prostate Cancer, Journal Club - Rashid Sayyid & Zachary Klaassen (Urotoday) - "In conclusion, the subsequent survival of men with newly diagnosed metastatic prostate cancer following the initiation of ADT is strongly and statistically significantly associated with baseline serum levels of bone metabolism biomarkers. These results can be employed by clinicians in counseling patients and by researchers in the design and conduct of future trials."

Biomarker • Video

Pilot Trial of Single Dose Ilofotase Alfa in Hypophosphatasia (clinicaltrials.gov) - P1/2 | N=12 | Recruiting | Sponsor: AM-Pharma

Biomarker • New P1/2 trial • ALPL

Study protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury. (PubMed, BMJ Open) - P3 | "US IND Number 117 605 Pre-results. gov number: NCT04411472."

Journal • P3 data • Acute Kidney Injury • Chronic Kidney Disease • Critical care • Infectious Disease • Nephrology • Novel Coronavirus Disease • Renal Disease • Septic Shock

(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI (clinicaltrials.gov) - P3 | N=661 | Terminated | Sponsor: AM-Pharma | N=1600 ➔ 661 | Trial completion date: Feb 2024 ➔ Aug 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2023 ➔ Aug 2022; The Data Monitoring Committee (DMC) concluded that the pre-specified futility threshold was met and that there was no safety concern.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock

(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI (clinicaltrials.gov) - P3 | N=1600 | Active, not recruiting | Sponsor: AM-Pharma | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock

Human Recombinant Alkaline Phosphatase (Ilofotase Alfa) Protects Against Kidney Ischemia-Reperfusion Injury in Mice and Rats Through Adenosine Receptors. (PubMed, Front Med (Lausanne)) - "In an AKI-on-CKD ischemic rat model, ilofotase alfa given after the third instance of IRI reduced injury. These results suggest that ilofotase alfa promotes production of adenosine from liberated ATP in injured kidney tissue, thereby amplifying endogenous mechanisms that can reverse tissue injury, in part through AR-and non-AR-dependent signaling pathways."

Journal • Preclinical • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • Reperfusion Injury • ADORA2A

Recombinant Human Alkaline Phosphatase in Healthy Japanese Subjects (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: AM-Pharma | Recruiting ➔ Completed

Trial completion

Recombinant Human Alkaline Phosphatase in Healthy Japanese Subjects (clinicaltrials.gov) - P1; N=32; Recruiting; Sponsor: AM-Pharma

Clinical • New P1 trial

AM-Pharma Announces Enrollment and Financing of COVID-19 Cohort in Phase III REVIVAL Trial (Businesswire) - "AM-Pharma B.V....announced that the first patients with COVID-19 infection and sepsis-associated acute kidney injury (SA-AKI) have been enrolled in the Company’s Phase III REVIVAL pivotal trial in an exploratory cohort...AM-Pharma received an innovation credit of up to EUR 5 million from the 'Netherlands Enterprise Agency' (RVO.nl)...For the Phase III REVIVAL trial, potentially over 100 sites across Europe and North America are actively recruiting patients with SA-AKI in the trial. Enrollment completion of 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."

Enrollment status • Financing • P3 data • Acute Kidney Injury • CNS Disorders • Novel Coronavirus Disease

(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI (clinicaltrials.gov) - P3; N=1600; Recruiting; Sponsor: AM-Pharma; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock

(Revival) Study to Investigate the Efficacy and Safety of Alkaline Phosphatase in Patients With Sepsis-Associated AKI (clinicaltrials.gov) - P3; N=1400; Not yet recruiting; Sponsor: AM-Pharma

Clinical • New P3 trial • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock

Inter-method variability for the measurement of bone alkaline phosphatase: Implication for the monitoring of CKD-MBD (KIDNEY WEEK 2013) - Abstract #FR-PO627; P=NA, N=81; "There is a significant problem in the b-ALP determination today which has clear clinical consequences. The variations among the methods are mainly due to assay drifted and reagents stability. The kit manufacturers should be keen to improve reagents stability, lot-to-lot variation and harmonization of the calibrations. The nephrologists should be aware that, just like PTH, b-ALP results are not transposable from one laboratory to the other."

Clinical • Renal Disease

AM-Pharma announces positive Phase I data on recAP for acute kidney injury (AM-Pharma Press Release) - P1, N=50; "AM‐Pharma...announces the results of its Phase I trial with both single and multiple ascending doses, which demonstrate that recAP is safe and well tolerated at all doses. The trial also established recAP’s pharmacokinetic properties. These include dose exposures up to and above the target therapeutic range as determined in AM-Pharma’s earlier positive Phase II clinical trial results with bovine Alkaline Phosphatase (bovine AP), in the treatment of patients with Acute Kidney Injury (AKI)."

P1 data • Acute Kidney Injury • Renal Disease

A Safety, Tolerability, Efficacy and QoL Study of Human recAP in the Treatment of Patients With SA-AKI (clinicaltrials.gov) - P2; N=290; Not yet recruiting; Sponsor: AM-Pharma

New P2 trial • Phase shift • Acute Kidney Injury • Biosimilar • Renal Disease

AM-Pharma returns to clinic with phase I trial of new recombinant human alkaline phosphatase (AM-Pharma Press Release) - "AM‐Pharma...announce that the first subjects have entered a Phase I trial of its recombinant AP (recAP) to treat Acute Kidney Injury (AKI). This is a significant milestone in the progress of AM-Pharma, as it re-enters the clinic with its new recombinant AP product. Recruitment to the trial will close in December 2013, with the results reporting in early 2014. Confirmation of the results seen in the previous bovine AP trials will enable the Company to seek approval for Phase II development in Q2 2014."

Anticipated enrollment status • Anticipated new P2 trial • Anticipated P1 data • Enrollment open • Renal Disease

AM-Pharma closes €12.2m financing round (AM-Pharma Press Release) - "AM‐Pharma...announces that it has closed a €12.2 million financing round led by Gilde Healthcare. The new capital enables the company to complete a 290 patient, four-arm, Phase II dose-finding, placebo-controlled, Phase III enabling study of recAP in Acute Kidney Injury (AKI), making it the largest ever therapeutic AKI trial."

Financing • Acute Kidney Injury • Renal Disease