ProKidney reports statistically significant results for Phase 2 REGEN-007 trial

ProKidney (PROK) reported statistically significant and clinically meaningful positive topline results from the full Group 1 modified intent-to-treat population of the Phase 2 REGEN-007 trial evaluating rilparencel in patients with CKD and diabetes. Rilparencel is an autologous cellular therapy that has received Regenerative Medicine Advanced Therapy designation from the U.S. Food & Drug Administration and is currently being evaluated in the ongoing Phase 3 REGEN-006 trial to demonstrate the therapy’s potential to preserve kidney function in patients with advanced CKD and type 2 diabetes. REGEN-007 is a multi-center Phase 2 open-label 1:1 randomized two-arm trial in patients with diabetes, CKD, and an estimated glomerular filtration rate of 20-50 mL/min/1.73m. At randomization, patients were assigned to one of two treatment groups using different dosing regimens. Group 1 replicated the dosing schedule of the ongoing Phase 3 PROACT 1 study in which patients received two scheduled rilparencel injections, approximately three months apart. Group 2 tested an exploratory dosing regimen to investigate whether disease progression triggers, rather than a time-based trigger, could optimize multiple administrations of rilparencel. In Group 2, patients received a single rilparencel injection in one kidney and a second injection in the contralateral kidney only if triggered by a sustained eGFR decline from baseline of greater than or equal to 20%, and/or an increase in the urine albumin to creatinine ratio from baseline of greater than or equal to 30% and greater than or equal to 30 mg/g. The prespecified primary endpoint for REGEN-007 is the difference in annual eGFR slope in the pre-injection period versus the period following the last rilparencel injection. The pre-injection period included all historical eGFR values collected up to 24 months before the screening visit as well as the on-study central laboratory eGFR results prior to first rilparencel injection. The period following the last injection included eGFR values from the last rilparencel injection to the end of study visit. Median follow-up after the last injection was approximately 18 months in both Group 1 and Group 2. Fifty-three patients were randomized in the study, of whom 49 patients received at least one rilparencel injection. Four patients did not receive any rilparencel injections. The majority of patients were male, and the mean age was 60 years. At baseline, 38 of 49 patients had type 2 diabetes mellitus and 11 had type 1 diabetes. Thirty-nine patients were receiving an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, and 18 were receiving a sodium-glucose cotransporter-2 inhibitor. At baseline, the mean eGFR was 33+/-10 mL/min/1.73m2. Notably, the median UACR was higher in Group 1 compared to Group 2. In Group 1, kidney function stabilized after receiving rilparencel. The annual decline in eGFR slope improved by 78% from -5.8 mL/min/1.73m2 in the pre-injection period to -1.3 mL/min/1.73m2 in the period following the last rilparencel injection. This 4.6 mL/min/1.73m2 per year difference1 was statistically significant and clinically meaningful. Of the 24 patients in Group 1, 15 met key Phase 3 PROACT 1 inclusion criteria, and similar efficacy results were observed in this subgroup compared to the full Group 1 results. As a reminder, the Phase 3 PROACT 1 protocol was amended in 1H 2024 after a similar eGFR efficacy signal was observed in the Phase 2 RMCL-002 study subgroup analysis of high-UACR, Stage 4 CKD patients with type 2 diabetes. In Group 2, the annual change in kidney function as measured by eGFR slope was -3.4 mL/min/1.73m2 in the pre-injection period versus -1.7 mL/min/1.73m2 in the period following the last rilparencel injection, resulting in an improvement of 50%, or 1.7 mL/min/1.73m2 per year. This difference was not statistically significant but suggests evidence of a dose response. Out of the 25 patients in Group 2, 15 met the re-dosing trigger and received a second rilparencel injection. The median time between the first and second injections in these 15 patients was approximately 11 months. No rilparencel-related serious adverse events were observed across all patients in the study who received at least one rilparencel injection. The safety profile was consistent with previously reported study results and comparable to a kidney biopsy. Full results from REGEN-007 are being held and will be submitted to the American Society of Nephrology 2025 Kidney Week as a late-breaking clinical trial.