Препарат тегопрубарт показал превосходство над такролимусом в лечении после трансплантации почки

Tegoprubart for maintenance therapy after kidney transplantation (KT) continues to show favorable outcomes compared with tacrolimus. Andrew Adams, MD, PhD, of the University of Minnesota, presented longer-term data from the phase 2 BESTOW trial at the American Transplant Congress (ATC). Tegoprubart is a humanized monoclonal antibody that was designed to inhibit CD40L and has been investigated in both allotransplantation and xenotransplantation settings. The phase 1b/2 trial BESTOW is a head-to-head superiority study with an ongoing long-term extension. Patients (n=19) undergoing KT received anti-thymocyte globulin (ATG) induction plus tegoprubart maintenance in the phase 1b portion of the trial and patients (n=127) undergoing KT were randomly assigned to receive ATG induction plus tegoprubart or tacrolimus in the phase 2 portion of the trial. All patients received mycophenolate and a corticosteroid taper. The long-term extension study included 84% of patients from phase 1b and 96% of tegoprubart and 82% of tacrolimus recipients from phase 2. The primary composite endpoint of this study is the rate of biopsy-proven acute rejection (BPAR), graft loss, death, and loss to follow-up. The 12-month findings have been reported. At 18 months, tegoprubart recipients had a significantly higher estimated glomerular filtration rate (eGFR) than tacrolimus recipients (74 vs 61 mL/min/1.73 m2; P <.05), respectively. The between-group difference in eGFR remained significant at 21 months (difference, 10 mL/min/1.73 m2) and 24 months (difference, 19 mL/min/1.73 m2). Among patients with BPAR, those who received tegoprubart had increasing eGFR over time compared with those who received tacrolimus, who had fluctuating eGFR. A subset of patients (n=5) switched to tegoprubart from tacrolimus after BPAR, which resulted in lower eGFR than those who remained on tacrolimus following BPAR. After 6 months of treatment, no additional BPAR events occurred in the tegoprubart treatment arm compared with 7 of 11 events in the tacrolimus treatment arm. In the safety analysis through 1 year, tegoprubart associated with lower rates of tremors (1.6% vs 25.0%), bacteremia (1.6% vs 10.9%), new-onset diabetes (1.6% vs 10.9%), hypertensive crisis (1.6% vs 7.8%), muscle spasms (4.8% vs 15.6%), pruritus (3.2% vs 9.4%), lymphopenia (6.3% vs 15.6%), sepsis (3.2% vs 7.8%), hyperkalemia (11.1% vs 26.6%), and hyperglycemia (9.5% vs 21.9%), but a higher rate of proteinuria (15.9% vs 1.6%) than tacrolimus, respectively. Through year 2, both interventions demonstrated robust safety profiles, with no graft loss or attributable deaths. The incident safety signals during tegoprubart treatment in the long-term extension included lower rates of diarrhea (10% vs 21%), herpes zoster (4% vs 8%), acute kidney injury (2% vs 6%), headache (2% vs 12%), bleeding (2% vs 8%), extremity pain (0% vs 10%), and fall (0% vs 6%) but higher rates of cytomegalovirus viremia (12% vs 6%) and BK viremia (8% vs 2%) compared with tacrolimus, respectively. Tegoprubart recipients reported significantly better Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) scores (mean difference [MD], -12.2; 95% CI, -19.7 to -4.6) and Kidney Disease Quality of Life (KDQOL-36) symptoms and problems scores (MD, 5.7; 95% CI, 1.0-10.5) at 52 weeks compared with tacrolimus recipients. There were no significant differences in other patient-reported outcomes. A phase 3 trial assessing tegoprubart after KT is planned. Tegoprubart also has been used in several landmark pig-to-human kidney transplant procedures. DISCLOSURE(S) (when applicable; for news) Disclosure: This research was supported by Eledon Pharmaceuticals. Please see the original reference for a full list of disclosures REFERENCE(S) (refer to Haymarket Style Guide and One Sheeter) References: Adams A. Phase 2 BESTOW trial: evaluating tegoprubart’s safety and efficacy in preventing kidney transplant rejection. American Transplant Congress (ATC); June 20-24, 2026; Boston, MA. Abstract 585.