TOPLINE:

In a phase 2a trial, a dual-biologic regimen of dazodalibep plus belatacept — used as an alternative to daily calcineurin inhibitors and corticosteroids after kidney transplantation — was generally safe and well-tolerated. In addition, it preserved kidney function, even in patients who experienced rejection, and was not associated with antibody-mediated rejection.

METHODOLOGY:

• Patients who undergo kidney transplantation generally require lifelong daily immunosuppressive therapy; these regimens improve short-term outcomes but cause significant toxicities, increase the risk for graft failure over time, and produce side effects that lead to nonadherence. Episodic, selective biologics targeting costimulation pathways could offer a less toxic alternative.
• This phase 2a, open-label, single-arm trial evaluated the efficacy and safety of combining dazodalibep and belatacept as the sole maintenance therapy in 23 patients (mean age, 47.7 years; 82.6% men) receiving first, nonidentical kidney transplants from deceased or living donors.
• Patients received lymphocyte-depleting induction with thymoglobulin and corticosteroids; intravenous dazodalibep and belatacept were given after transplant on day 1 and at specific timepoints until week 48. Patients were followed up for an additional 12-week safety period after study drug discontinuation.
• After two of the first three dosed patients experienced transplant rejection, the protocol was amended to increase the thymoglobulin dose and to implement a revised dazodalibep/belatacept dosing regimen for subsequently enrolled patients (n = 20).
• The primary endpoint was the incidence of efficacy failure — defined as treated biopsy-proven acute rejection (grade 1A or higher), graft loss, or death — at week 24, and secondary endpoints included the evaluation of the individual efficacy components at weeks 12, 24, and 48 and safety assessments.

TAKEAWAY:

• Among the 23 patients who received dazodalibep and belatacept, 56.5% completed the trial, whereas the remaining discontinued due to various reasons including adverse events, physician guidance, patient withdrawal, and graft rejection.
• The efficacy failure rate was 25% (5/20) at weeks 12, 24, and 48 among patients who received the revised dosing regimen; no antibody-mediated rejections were observed.
• At week 48, patients who were evaluable for efficacy had a mean estimated glomerular filtration rate of 71.3 mL/min/1.73 m²; values were similar between patients who did and did not experience rejection; kidney function recovered after standard-of-care “rescue” therapies in patients with rejection.
• Most patients (95.7%) experienced at least one treatment-emergent adverse event, although no thrombotic events were observed, and both graft and patient survival were 100%.

IN PRACTICE:

“Findings from this trial suggest that dual costimulation immunosuppression may represent a viable therapeutic option as sole maintenance therapy for kidney and other organ transplant recipients,” the authors wrote.

SOURCE:

This study was led by Flavio Vincenti, MD, Department of Medicine and Department of Surgery, University of California San Francisco. It was published online on February 3, 2026, in the American Journal of Transplantation.

LIMITATIONS:

The trial was limited by its small sample size. The high threshold set for meeting the primary efficacy endpoint and a cautious approach to discontinuing study therapy were additional limitations. Factors such as dosing, monitoring, and clinician/patient comfort with the regimen were in early stages.

DISCLOSURES:

This study was funded by Amgen Inc (formerly Horizon Therapeutics plc). One author reported receiving grant support from Amgen Inc. Another author reported being a member of the board of directors for Eledon Pharmaceuticals, Inc. Two authors disclosed being employees of Amgen Inc and owning company stock.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.