AlloVir, Inc. announced positive final results from a Phase 2 study of posoleucel, an investigational, allogeneic, off-the-shelf, multi-virus-specific T cell (VST) therapy, being studied for the treatment of BK viremia (BKV) in adult kidney transplant recipients. The data support the safety and antiviral activity of posoleucel in this population, which has no effective BKV treatment options. In the randomized, double-blind, placebo-controlled study, posoleucel was shown to be generally well tolerated, with balanced safety across the two posoleucel dosing groups and placebo.

Patients who received posoleucel achieved a clinically meaningful greater decline in BK viral load compared with those receiving placebo. The study results showed an even greater antiviral effect with posoleucel in patients with BK viral load =10,000 copies/mL at screening and in the biweekly posoleucel dosing group, identifying a dosing regimen and patient population to advance into a future trial. This Phase 2 study evaluated the safety and efficacy of posoleucel to treat BK viremia in adult kidney transplant recipients with BK viral load between 350-10,000,000 copies/mL (stratified by low (<10,000 copies/mL) or high (=10,000 copies/mL) viral load at study screening).

Sixty-one patients were randomized 1:1:1 to receive one of two dosing regimens of posoleucel – weekly administration of posoleucel for three weeks, then every two weeks, or weekly administration of posoleucel for three weeks, then once a month – or placebo over 12 weeks. Following this dosing period, patients were followed through Week 24. Of the 61 enrolled patients, 58 patients completed the study through Week 24; two patients were lost to follow-up and one patient withdrew consent.

The primary endpoint of the study was safety and tolerability of posoleucel versus placebo. Across all patients who received at least a single dose of study drug, posoleucel was well tolerated. The incidence and severity of adverse events were consistent with the underlying patient population and background immunosuppression.

Low rates of infusion reactions were observed in patients receiving posoleucel (2%) and those receiving placebo (5%). There were no deaths or reports of graft versus host disease or cytokine release syndrome. Emergence of donor-specific antibodies was uncommon and occurred with similar frequency in patients receiving posoleucel (7%) or placebo (5%).

Three patients who received posoleucel were reported to have acute rejection per biopsy report by a central reader: one who was clinically diagnosed with, and successfully treated for, renal tuberculosis, one who had rejection on a biopsy prior to posoleucel dosing during the screening window, and one who developed rejection at Week 22 of the trial. None of these cases were assessed by the investigator as related to study drug. The key secondary endpoint of the study was the change in BK viral load in patients receiving posoleucel versus those receiving placebo.

The efficacy analysis excluded six patients in whom significant reductions in immunosuppression were made immediately prior to study entry. Posoleucel achieved greater viral load reductions versus placebo consistently across multiple BK viral load measures. This clinically meaningful treatment effect was strongest among patients receiving posoleucel every two weeks and among those with high viral loads.

Antiviral responses among posoleucel patients increased over time, with maximal responses observed at Week 24. Renal function in this group remained stable throughout the study, with a median change in estimated glomerular filtration rate from baseline to Week 24 of 0 mL/min/1.73m2 in the overall posoleucel group and 0 mL/min/1.73m2 in the placebo group.