Guard Therapeutics has announced the enrollment of 25% of the targeted patients in its Phase 2b POINTER study. This trial is designed to evaluate the potential kidney-protective effects of RMC-035 in individuals undergoing open-heart surgery, a procedure often associated with acute kidney injury (AKI). The next significant milestone is the result of the first of two independent, blinded safety analyses, anticipated in the first quarter of 2025.
POINTER Study Details
The POINTER study is a randomized, double-blind, and placebo-controlled Phase 2b trial. It aims to determine the optimal dosing regimen and target patient population for a future pivotal Phase 3 study of RMC-035. The trial plans to enroll approximately 160 patients, with at least 30% having chronic kidney disease (CKD), defined as an eGFR (estimated glomerular filtration rate) less than 60 mL/min/1.73m2. Participants are being randomized into two different dose arms of RMC-035 (60 mg and 30 mg) and a placebo arm in a 2:2:3 ratio. Renal function before surgery is a stratification factor, ensuring even distribution of patients with and without CKD across all treatment arms.
The primary endpoint of the study is the change in eGFR from study entry to 90 days post-surgery, aligning with the study's planned follow-up duration. A key secondary endpoint is Major Adverse Kidney Events (MAKE) at 90 days post-surgery, encompassing death, dialysis treatment, or a ≥ 25% reduction in eGFR compared to pre-surgery levels. Data from the two RMC-035 dose arms will be pooled for primary efficacy analyses against the placebo group.
RMC-035: A Novel Therapeutic Approach
RMC-035 represents a first-in-class drug, a recombinant and modified variant of the endogenous protein alpha-1-microglobulin. This investigational drug is designed to protect cells and their mitochondria from damage induced by oxygen deprivation and elevated levels of heme, a toxic protein that binds oxygen. Preclinical studies have shown favorable treatment effects of RMC-035 across several disease models. RMC-035 exhibits a natural affinity for the kidneys and is being developed as an intravenous kidney-protective treatment for patients at high risk of developing AKI.
RMC-035 has received Investigational New Drug (IND) clearance from the FDA for AKI treatment in open-heart surgery. It also holds Fast Track Designation from the FDA to reduce the risk of irreversible kidney function loss, the need for dialysis, or death following open-heart surgery in high-risk AKI patients. Results from the Phase 2 AKITA study, involving 177 patients, demonstrated a statistically significant and clinically relevant positive effect of RMC-035 on long-term kidney outcomes in this patient population. RMC-035 has also been evaluated in a Phase 1b clinical study in kidney transplant patients.
Addressing Kidney Injury in Open-Heart Surgery
Open-heart surgery, often involving coronary artery bypass grafting (CABG), can lead to significant kidney damage, primarily due to ischemia-reperfusion injury, where blood flow and oxygen supply to the kidneys are reduced. Hemolysis, the breakdown of red blood cells, also contributes by releasing harmful hemoglobin byproducts that damage the kidneys. This process is exacerbated by extracorporeal blood circulation through the heart-lung machine and blood transfusions, common during the procedure. The resulting oxygen deprivation and hemolysis can trigger an inflammatory response, further increasing the risk of scarring and permanent kidney function loss.
Management Perspective
"Following the study launch in Canada in August and subsequent initiation in Europe in October, all participating sites are now open for patient recruitment. It is encouraging to see patients dosed across all countries involved, and a strong motivator for the continued execution of the POINTER trial," stated Tobias Agervald, CEO of Guard Therapeutics. He also noted that the company plans to communicate the overarching conclusions and recommendations regarding the trial’s continuation after the independent safety analyses, although the analyses will remain blinded to the company.
