T Cell Therapy for Post-Transplant Virus Prevention Granted RMAT Designation

An investigational T cell therapy, posoleucel, has been granted regenerative medicine advanced therapy (RMAT) designation by the FDA for prevention of infection from 6 viruses that commonly affect people who have undergone allogeneic hematopoietic cell transplant (allo-HCT).¹

The multi-virus-specific cell therapy, from AlloVir, is intended to prevent clinically significant infection or disease from adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6), and JC virus (JCV), any one of which are often reactivated in patients receiving allo-HCT.

The allogeneic, off the shelf therapy, which is currently being studied for this indication in an ongoing open-label phase 2 trial as well as a phase 3 trial, could potentially be used as prophylactic or preemptive therapy in this immunocompromised population.

Recently presented data from the phase 2 CHARMS trial (NCT04693637) demonstrated good safety and efficacy among those who received at least 1 dose of posoleucel, with 3 reported clinically significant infections through week 14 in 26 participants, of whom 46% received cells from haploidentical donors, 35% from mismatched unrelated donors, 15% from matched unrelated donors with T cell depletion or with lymphopenia, and 4% from umbilical cord blood. Among the 24 participants who reached the 14-week end point, 21 remained free of clinically significant infections. Of the 3 patients who experienced infection, 2 initiated preemptive CMV treatment with valganciclovi4 and 1 started rituximab for EBV. No unanticipated safety signals were observed, with rates and severity of graft versus host disease lower than those typically expected in this high-risk population.

“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 Sanjeet Dadwal, MD, chief, Division of Infectious Diseases and professor of medicine, and posoleucel study investigator, in a previous statement.² “These new data continue to support the potential for posoleucel to prevent infections caused by these 6 viruses that can lead to significant morbidity and mortality in a vulnerable patient population with limited to no effective treatment options.”

The recently launched phase 3 multicenter, randomized, double-blind, placebo-controlled trial (NCT05305040) will include a target enrollment of 302 allo-HCT patients who will receive 7 2 to 4 mL infusions of posoleucel or placebo over 12 weeks, followed by a 12-week follow-up period. The primary end point is number of clinically significant infections or episodes of end-organ disease through 14 weeks, while secondary outcomes will evaluate infection and disease rates through week 26, viral load through week 26, adverse events, and overall and non-relapse mortality.

Posoleucel is also the subject of 2 additional phase 3 clinical trials for treatment of virus-associated hemorrhagic cystitis caused by BKV (NCT04390113) and treatment of AdV following allo-HCT, both of which received RMAT designation from the FDA. A phase 2 study (NCT04605484) for treatment of BKV in kidney transplant recipients is ongoing.

AlloVir is also exploring virus-specific T cell therapies in other populations and indications, including ALVR106, which targets human metapneumovirus, influenza, parainfluenza virus, and respiratory syncytial virus in patients undergoing allo- or auto-hematopoietic stem cell transplant and general high-risk populations; ALVR107 targeting hepatitis B; and ALVR109 targeting COVID-19.

REFERENCES

1. FDA Grants Regenerative Medicine Advanced Therapy (RMAT) Designation to AlloVir’sPosoleucel for Prevention of Multiple Life-Threatening Infections from Six Viruses in Allogeneic Hematopoietic Cell Transplant Patients. News release. AlloVir. April 20, 2022. https://ir.allovir.com/news-releases/news-release-details/fda-grants-regenerative-medicine-advanced-therapy-rmat-0

2. 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. News release. AlloVir. March 22, 2022. https://ir.allovir.com/news-releases/news-release-details/allovir-initiates-global-phase-3-registrational-study-posoleucel