AlloVir Initiates Global Phase 3 Registrational Study of Posoleucel for Prevention of Life-Threatening Viral Infections from Six Common Viruses in High-Risk, Allogeneic Hematopoietic Cell Transplant Patients
Updated, preliminary Phase 2 data presented at EBMT Annual Meeting continue to demonstrate substantial reduction in the expected rate of clinically significant infections with posoleucel therapy
21 of 24 patients were free of clinically significant infections through the Week 14 primary endpoint
Posoleucel has the potential to fundamentally transform the treatment landscape for allo-HCT by preventing life-threatening viral diseases and infections, either as a prophylactic therapy in high-risk patients or as a preemptive therapy in patients who have already reactivated one or more of the six viruses targeted by posoleucel. As 90% of allo-HCT patients reactivate at least one of these viruses, there is a large global market opportunity for the prevention of devastating viral diseases, with an estimated addressable patient population of 40,000 allo-HCT patients annually.
Initial Phase 2 data supporting the use of posoleucel to prevent life-threatening infections from six common viruses following allo-HCT were presented in
“Hematopoietic cell transplantation leaves patients at high risk for multiple viral infections or disease that cause patients significant suffering, prolonged hospitalization, and threaten the graft and patient survival. These viral infections are all too common, with two-thirds reactivating multiple viruses in the first 100 days post-transplantation,” said
“The clinical data presented at EBMT continue to demonstrate the transformative potential of posoleucel, a multi-virus-specific T-cell therapy, for immunocompromised patients,” said
Preliminary Study Findings
This multi-center, open-label, randomized, double-blind, placebo-controlled, Phase 2 study is evaluating the efficacy and safety of posoleucel for the prevention of six potentially life-threatening viral infections – AdV, BKV, CMV, EBV, HHV-6 and JCV – in 26 high-risk allo-HCT patients. Patients receive up to seven biweekly posoleucel infusions and are tested for viremia by polymerase chain reaction (PCR) on a weekly basis against all six viruses over a period of 14 weeks. Following this dosing period, patient follow-up extends through Week 26.
At the time of the data cut-off for this preliminary analysis, all 26 patients received at least a single dose of posoleucel. Twenty-four patients have completed dosing through Week 14, and the evaluation of two patients for the primary endpoint is ongoing. Of the enrolled patients, 12 (46%) received cells from haploidentical donors, nine (35%) from mismatched unrelated donors, four (15%) from matched unrelated donors with T cell depletion or with lymphopenia, and one (4%) from umbilical cord blood.
In this preliminary analysis, high-risk allo-HCT patients receiving posoleucel had rates of clinically significant viral infections substantially lower than the approximately 70% expected in this population, as estimated through an analysis of peer-reviewed published data and electronic medical record reviews.
The primary study endpoint is the number of new-onset clinically significant infections or end-organ disease through Week 14. Among the 26 patients who received at least a single dose of posoleucel, only three of 156 possible clinically significant infections from these six common and life-threatening viruses were observed in three patients through 14 weeks. Specifically, two patients initiated preemptive CMV treatment with valganciclovir, and one patient started rituximab for EBV in the setting of receiving high-dose steroids and progressed to post-transplant lymphoproliferative disease.
Repeat posoleucel dosing has been generally well-tolerated, with no unanticipated safety signals. The observed rates and severity of graft versus host disease were lower than those expected in this high-risk allo-HCT patient population. Three (12%) treatment-related serious adverse events were reported.
In addition to clinical data, initial biomarker data were also presented, demonstrating the expansion and persistence of posoleucel cells among patients with available data at the time of this analysis. Of the nine patients with available T cell receptor sequencing data, all had detectable posoleucel cells, with confirmed persistence for up to 14 weeks after the last infusion. A preliminary assessment of virus-specific T cell activity against the infecting virus by IFN-γ ELIspot demonstrated expansion following transient viremia.
AlloVir’s lead product, posoleucel (Viralym-M, ALVR105), is in late-stage clinical development as an allogeneic, off-the-shelf, multi-virus specific T-cell therapy targeting six viral pathogens in immunocompromised individuals: adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and JC virus (JCV). In the positive Phase 2 proof-of-concept CHARMS study, more than 90% of patients who failed conventional treatment and received posoleucel demonstrated a complete or partial clinical response based on predefined criteria, most with complete elimination of detectable virus in the blood and resolution of major clinical symptoms. FDA has granted posoleucel Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of hemorrhagic cystitis (HC) caused by BKV and for the treatment of adenovirus (AdV) infection in adults and children following allo-HCT, and Orphan Drug Designation for the treatment of virus-associated HC. The
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