ProKidney’s Diabetes and CKD Cell Therapy Rilparencel Improves eGFR Slope Annual Decline in Phase 2 Trial
Alongside the new data from REGEN-007, ProKidney also announced that it will be attending a Type B meeting with the FDA later in the summer.
ProKidney’s rilparencel (also known as REACT), a renal autologous cell therapy intended to treat diabetes and chronic kidney disease (CKD), has improved annual decline in estimated glomerular filtration rate (eGFR) slope in patients treated in the phase 2 REGEN-007 clinical trial (NCT05018416).1
The multicenter, open-label REGEN-007 trial randomly assigned participants into 2 different treatment groups in a 1:1 fashion. In group 1, patients received an injection of rilparencel into 1 kidney and then another injection of rilparencel into the other kidney 3 months later.1,2 In group 2, patients initially received an injection of rilparencel into 1 kidney, but only received a second injection into the other kidney if their eGFR showed a sustained reduction of 20% or more or if their urine albumin to creatinine ratio (UACR) showed an increase from baseline of 30% or more and 30 mg/g or more.
The 24 patients in group 1 who received rilparencel showed stabilization of kidney function following treatment, with a 78% improvement in annual decline in eGFR slope from -5.8 mL/min/1.73m2 pretreatment to -1.3 mL/min/1.73m2 posttreatment, a difference of 4.6 mL/min/1.73m2 per year considered statistically significant (P < .001) and clinically meaningful.
The 25 patients in group 2 who were treated with rilparencel showed a 50% improvement in in annual decline in eGFR slope from -3.4 mL/min/1.73m2 pretreatment to -1.7 mL/min/1.73m2 after treatment with the last rilparencel injection, a difference of 1.7 mL/min/1.73m2 per year. ProKidney pointed out that this difference is not statistically significant (P = .085) but indicated it “suggests evidence of a dose response”. Furthermore, the company noted that 60% of the patients (n = 15) in group 2 received a second injection of rilparencel, having hit a redosing trigger, and that the median time between the first and second injection for these patients constituted about 11 months.
With regard to safety, there were no rilparencel-related serious adverse events reported in any of the 49 patients who received the cell therapy across groups 1 and 2. ProKidney characterized the safety profile as comparable to a kidney biopsy, and in line with study results that have previously been reported.
REGEN-007 randomly assigned 53 participants in total to either group 1 or group 2, but only 49 patients ultimately received at least 1 rilparencel injection. The patients had a mean age of 60 years and a majority are men (69%). Type 2 diabetes was present in 38 of the 49 treated patients (78%) at baseline and type 1 diabetes was present in 11 of the 49 treated patients (22%) at baseline. Furthermore, 39 patients (80%) were being treated with angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker and 18 patients (37%) were being treated with a sodium-glucose cotransporter-2 inhibitor. The mean (SD) eGFR at baseline was 33±10 mL/min/1.73m2, and ProKidney highlighted that group 1 patients had a median UACR of 792 mg/g, while group 2 patients had a median UACR of 229 mg/g. Difference in annual eGFR slope in the period before and after treatment, which constitutes the trial’s prespecified primary end point, was calculated via a linear mixed effects model. All historical eGFR values collected up to 24 months prior to screening and on-study central laboratory eGFR data were used to constitute the pretreatment period. The posttreatment period constitutes eGFR data from the last rilparencel injection to end of the study visit, and ProKidney noted that a median follow-up time from last injection of about 18 months was available for both groups 1 and 2.
In addition to REGEN-007, rilparencel is also being evaluated in the phase 3 REGEN-006 (PROACT 1) clinical trial (NCT05099770) for patients in the United States who have type 2 diabetes or CKD. Alongside the new data from REGEN-007, ProKidney also announced that it will be attending a Type B meeting with the FDA later in the summer in which the agency will confirm whether using eGFR slope as a surrogate end point for PROACT 1 will be acceptable for supporting accelerated approval.
“We are very encouraged by the REGEN-007 topline results that demonstrated a robust improvement in eGFR slope following treatment with rilparencel in group 1 as well as evidence of a dose response in group 2,” Bruce Culleton, MD, the chief executive officer of ProKidney, said in a statement.1 “These data bolster our confidence in the design of our ongoing phase 3 PROACT 1 study given the similarity between the dosing regimen in REGEN-007 group 1 and PROACT 1. It is also worth noting that 15 of the 24 patients in group 1 (63%) met key phase 3 PROACT 1 inclusion criteria, and similar efficacy results were observed in this subgroup compared to the full group 1 results. We plan to submit the full results from REGEN-007 to ASN’s 2025 Kidney Week as a late-breaking clinical trial and are excited to share more details at that time with investors and the medical community. We also look forward to our upcoming FDA Type B meeting in the coming weeks to confirm our approach to eGFR slope as a surrogate endpoint for accelerated approval. This meeting represents an important step toward our goal of expediting rilparencel’s potential path to market in the US where there remains a significant unmet clinical need in patients with advanced CKD and diabetes.”
Notably, in September of last year, ProKidney announced that it was putting a new strategic focus on PROACT 1.2 On the other hand, the company reported that it would be discontinuing the phase 3 REGEN-016 (PROACT 2) clinical trial (NCT05286853), which was evaluating rilparencel in patients with type 2 diabetes and CKD in Spain based on a comprehensive analysis that suggested PROACT 2 would not be necessary to achieve regulatory approval of rilparencel in the US.
