In a Phase 2 open-label study of patients with advanced CKD and diabetes, bilateral renal injections of rilparencel improved the annual eGFR slope by 4.6 mL/min/1.73m2 (78%; p<0.001) in Group 1 (n=24), with a larger effect in the subgroup meeting PROACT 1 Phase 3 criteria at 5.5 mL/min/1.73m2 (85%; p=0.005). An exploratory regimen in Group 2 (n=25) delivered a 1.7 mL/min/1.73m2 improvement (50%; p=0.085). No therapy-related serious adverse events were reported, and the procedure’s safety profile aligned with biopsy-level risk. ProKidney presented complete Phase 2 REGEN-007 results at ASN Kidney Week and tied the readout to its ongoing registrational Phase 3 program, REGEN-006 (PROACT 1). FDA previously confirmed that eGFR slope is an acceptable surrogate endpoint for accelerated approval in this program and that the same trial may support both accelerated and confirmatory approval. More than half of the approximately 360 patients needed for the slope-based accelerated analysis have been enrolled, with topline data expected in Q2 2027. Rilparencel, an autologous cell therapy administered by bilateral kidney injections roughly three months apart, is positioned as an add-on to standard care in a setting with high progression risk and limited interventional options. The strategy is clear: leverage a surrogate endpoint the agency has endorsed for this program to move a first-in-category renal cell therapy through a single registrational pathway, while de-risking safety via a procedure already familiar to nephrology sites.
The Phase 2 design underscores both the promise and the tension. Both arms received rilparencel, differing only in dosing paradigm, and efficacy was assessed by pre- versus post-treatment slope within individuals rather than a concurrent standard-of-care control. The stronger signal with the fixed, two-dose regimen and a weaker, non-significant effect when re-dosing was triggered by progression hint at a dose–response relationship, but also leave open questions about durability, optimal timing, and the magnitude of benefit on top of SGLT2 inhibitors and GLP‑1 receptor agonists in routine practice. Post hoc subgroup patterns suggesting incremental benefit over background therapy will need to be prospectively confirmed. Operationally, the program pushes sites beyond oral add-on paradigms toward interventional nephrology workflows: bilateral cortical injections, imaging support, chain-of-identity for autologous product, and tight scheduling for two procedures approximately three months apart. CROs and sponsors should expect greater coordination across cell processing, shipment, and lot release, along with higher demands on retention and lab frequency to support slope modeling. For regulators, the absence of a concurrent SOC control in Phase 2 elevates the importance of Phase 3’s statistical rigor, background therapy standardization, and adjudication of renal endpoints. For payers and HTAs, any accelerated approval on slope will likely be tied to confirmatory outcomes and clear evidence of incremental effect on top of modern SOC. The next catalysts are straightforward but nontrivial: sustained enrollment velocity into a complex procedural trial, early operational readouts on manufacturing throughput and site performance, and clarity on confirmatory outcome measures beyond slope, such as time to kidney failure or sustained eGFR decline. The key risks are executional—manufacturing scale, site capability, and patient adherence—and evidentiary, including the need to show consistency across diverse CKD phenotypes and concomitant therapies. If PROACT 1 can reproduce the Phase 2 Group 1 signal with tight control of background medications and minimal data loss, rilparencel could test whether a procedure-based, autologous approach can fit within kidney care pathways increasingly optimized around well-tolerated orals. Watch for interim operational metrics and any guidance on confirmatory endpoint timing—those will signal how quickly this pathway can translate into a viable label and reimbursement framework.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
