Antiviral responses increased until peaking at week 24.
Posoleucel (AlloVir) cell therapy has shown efficacy in treating patients with BK viremia who have received a kidney transplant in new data from a phase 2 trial (NCT04605484).
Participants treated with posoleucelhad a clinically meaningful decline in BK viral load compared to those treated with placebo, with a greater effect observed in patients with a viral load of at least 10,000 copies/mL at screening, and with patients treated biweekly.
"BKV is one of the most feared transplant-associated viral infections, due to the lack of available effective antiviral therapies and its profoundly negative impact on transplant outcomes,” principal investigator Anil K. Chandraker, MD, Director, Renal Transplant Medicine, Brigham and Women's Hospital, said in a statement. "The safety profile of posoleucel and its antiviral activity, which is amplified in high viral load patients who have the greatest unmet need, suggest it could potentially offer a transformative treatment option for kidney transplant patients with BK viremia.”
The phase 2 study enrolled 61 patients, 58 of which completed the study through week 24 (2 lost to follow-up and 1 withdrew consent). Participants had a BK viral load between 350-10,000,000 copies/mL (stratified as high or low) and were randomized 1:1:1 to receive either weekly administration for 3 weeks followed by biweekly administration for a total of 12 weeks, or weekly administration for 3 weeks, then once a month or placebo over 12 weeks. Participants were then followed through week 24.
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Investigators found that repeat administration of posoleucel was well tolerated across dosing groups and placebo, with adverse events (AEs) consistent with the patient population and immunosuppression. Participants receiving both posoleucel (2%) and placebo (5%) experienced infusion reactions at similar rates; similarly, participants had similar rates of donor-specific antibody emergence between posoleucel (7%) and placebo (5%). There were no deaths, cases of graft-versus-host disease, or cases of cytokine release syndrome. Additionally, 3 treated patients had acute rejection assessed to be unrelated to posoleucel.
"This study is the first to evaluate a virus-specific T cell therapy in solid organ transplant patients, with the primary goal of exploring the safety of posoleucel treatment for BK viremia in kidney transplant patients. We are pleased with the consistency of posoleucel’s safety profile across solid and stem cell transplant patient populations and with the important antiviral efficacy results in kidney transplant patients at highest risk for BKV-associated graft loss observed in this study," Diana Brainard, MD, chief executive officer, AlloVir, added to the statement. “We believe today's results are an important and compelling milestone not just for AlloVir but for the entire kidney transplant community."
The trial’s secondary endpoints assessed efficacy and found that at week 24, 39% (n = 15/38) of patients who received posoleucel experienced a ≥1-log viral load reduction, more than double the placebo rate (14%; 2/14). This rate was higher at 50% in the biweekly dosing group (n = 10/20), followed by 28% (n = 5/18) in the monthly dosing group and 14% (n = 2/14) in the placebo group. In patients categorized as having a high viral load, 69% (n = 11/16)of treated participants overall and 75% (6/8) of biweekly treated participants, achieved a ≥1-log viral load reduction compared with 25% (n = 1/4) of patients in the placebo group. The efficacy analysis excluded 6 patients that had significant reductions in immunosuppression immediately prior to study entry. Overall, antiviral responses increased over time, and peakedat week 24, and renal function remained stable throughout the study.
“These safety and efficacy data in solid organ transplant patients provide important insights into the potential of posoleucel, which is also being studied in our three ongoing Phase 3 registrational trials in allo-HCT patients. We look forward to working with regulatory authorities and transplant specialists on our forward-looking clinical development strategy in kidney transplant patients, and potentially other solid organ transplant recipients,” Dr. Brainard added.
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