Dual Costimulation Blockade May Eliminate Daily Oral Immunosuppression in Kidney Transplant

A pilot trial evaluating dual costimulatory blockade, dazodalibep + belatecept, may promote immunosuppression adherence and present a non-calcineurin treatment option for kidney transplant recipients.1

The phase 2a pilot trial is the first clinical trial to evaluate dual costimulation blockade in humans, with study investigators reporting that a significant number of patients did not require any daily oral medications for 1 year.1

“That's never been done,” said Allan Kirk, MD, PhD, a transplant surgeon at Duke Kidney/Transplant Clinic, in an interview with HCPLive. “All immunosuppressive regimens have involved at least some oral medication every single day. And this just showed proof of concept that you could do episodic therapy instead of daily therapy. And I think for patients that's a big plus.”

In a previous interview, we broke down the mechanistic rationale and history of targeting the costimulatory pathway with Kirk.2

Methods/Trial Design

Kirk and fellow study investigator concluded the phase 2a, open-label, single-arm, pilot trial to evaluate the efficacy, safety, and tolerability of dual costimulation blockade, dazodalibep and belatacept, in adult recipients of a first, human leukocyte antigen (HLA)–nonidentical kidney allograft from a deceased, living unrelated, or living related donor.1

The mean cumulative amount of dazodalibep and belatacept each patient received during the course of the trial was 18,673.9 mg and 6,975.8 mg, respectively.1

After administration of dazodalibep and belatacept, patients returned to the transplant center for safety monitoring and costimulation-blockade therapy administration on day 7 and week 2, then every 2 weeks for 5 visits, and then monthly for 9 visits until week 48. All patients were monitored for acute rejection, graft survival, and patient survival through week 48. Patients were followed for a 12-week safety follow-up period after discontinuation of the investigational regimen and conversion to standard-of-care management at the investigator’s discretion.1

Investigators deemed the primary endpoint as the incidence of efficacy failure, defined as treated biopsy-proven acute rejection (tBPAR) ≥ grade 1A, graft loss, or death at week 24 after transplantation. The secondary endpoints were the incidence of tBPAR, graft loss, death, or loss to follow-up; incidence of antibody-mediated rejection; incidence of biopsy-proven acute rejection; incidence of treated acute rejections; the proportion of patients with de novo DSAs; as well as the safety and tolerability of dual costimulation. These were evaluated at weeks 12, 24, and 48.1

Additional exploratory endpoints included the proportion of patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at weeks 12, 24, and 48. The safety endpoints were treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs).1

The trial population included 23 patients, 18 to 70 years of age. Of the 23 enrolled patients who received dazodalibep and belatacept, 13 completed and 10 discontinued the trial. All patients discontinuing either dazodalibep and/or belatacept entered the safety follow-up.1

Results

Upon analysis, investigators reported the incidence of composite efficacy failure was 25% (5/20) at weeks 12, 24, and 48. Additionally, there were reversible rejections in patients who received transplants from living related donors (n = 3), a living unrelated donor (n = 1), and a deceased heart-beating donor (n = 1). Overall, they observed 100% graft and patient survival, with 1 patient experiencing delayed graft function.1

Investigators did not observe any patients with antibody-mediated rejections, sharing that 30% had treated acute rejections by week 48 (n = 6). Of these, 5 were diagnosed within 12 weeks of transplantation.1

The mean (SD) eGFR for all efficacy-evaluable patients at week 48 was 71.3 (12.7) mL/min/1.73 m2 and was similar for patients who did or did not experience an episode of rejection. The percentage of evaluable patients with an eGFR ≥60 mL/min/1.73 m2 was 59%, 74%, and 92% at weeks 12, 24, and 48, respectively.1

“This means that people on this approach need to be monitored carefully and early if you catch a rejection, it's easy to reverse,” explained Kirk.

Editor’s Note: Kirk reports relevant disclosures with Ededon Pharmaceuticals.

Reference

1. Vincenti F, Shoji J, Wojciechowski D, et al. Dual costimulation blockade with the CD154-specific fusion protein dazodalibep and belatacept for prophylaxis of kidney allograft rejection. American Journal of Transplantation. 2025;0(0). doi:https://doi.org/10.1016/j.ajt.2025.12.290

2. Kirk A, Hillenbrand A. Mechanistic Rationale for Dual Costimulation Blockade, Belatacept, Dazodalibep in Kidney Transplantation. HCPLive. Published February 18, 2026. Accessed February 19, 2026. https://www.hcplive.com/view/mechanistic-rationale-for-dual-costimulation-blockade-belatacept-dazodalibep-in-kidney-transplantation