Phase I Study of “Off-The-Shelf” Virus-Specific T Cells Published in BLOOD ADVANCES
- Mini-bank of T-cell lines generated from only 8 selected third-party donors can effectively supply greater than 95% of transplant recipients with a potent virus-specific T cell therapy
- Study demonstrates that third party virus-specific T-cell lines selected based solely on HLA match provide therapeutic benefit without serious adverse events
- Study validates approach for AlloVir’s upcoming Pivotal Phase III trials in multi-virus T-cell therapy
Houston, Texas - September 10, 2019 – Research published in the journal BLOOD ADVANCES established the feasibility of using a small bank of third-party cell lines generated from carefully chosen donors to provide virus-specific T-cell therapy to a large number of patients. The data show coverage of more than 95 percent of patients with cytomegalovirus (CMV) reactivation and associated diseases following allogeneic hematopoietic stem cell transplantation (HSCT). The Phase 1 study was conducted by researchers at Baylor College of Medicine’s Center for Cell and Gene Therapy, whose innovative technology platform formed the basis for AlloVir, a late-clinical stage allogeneic cell therapy company. The study established and used a bank of CMV-specific T cells (CMVSTs), derived from just eight CMV seropositive donors with HLA types representing the diverse U.S. population, as an “off the shelf” therapy to treat drug-refractory CMV-associated diseases. The data indicate that a “mini” bank of cell lines from a small number of well-chosen third-party donors can potentially supply the majority of patients with an appropriately partially HLA-matched line that produces anti-CMV activity post-HSCT without serious adverse events.
This research formed the basis of AlloVir’s current pipeline of multi-virus T cell therapies. AlloVir’s lead therapy Viralym-M (ALVR105) is in late-stage clinical development as an allogeneic, off-the-shelf multi-virus specific T-cell therapy targeting six common viral pathogens. The company is also advancing ALVR106 as an allogeneic, off-the-shelf multi-virus specific T-cell therapy that targets four common and devastating community-acquired respiratory viruses. AlloVir plans to initiate pivotal Phase III studies with Viralym-M and a proof-of-concept study with ALVR106 in 2019-2020. In June, AlloVir received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA) for Viralym-M.
“The data demonstrate that AlloVir’s proprietary manufacturing platform potentially enables us to serve a very broad population of patients with life-threatening virus-associated diseases with a very small bank of virus-specific T cells,” said Ann Leen, Ph.D., co-founder and chief scientific officer of AlloVir. “This validates the approach we will be implementing in our upcoming pivotal Phase 3 trials with our lead therapy, Viralym-M.”
About The Study
This was a single center Phase 1 study (NCT02313857) open to allogeneic HSCT recipients with post- transplant CMV infections or disease that had persisted for at least seven days despite standard therapy defined as treatment with ganciclovir, foscarnet or cidofovir. Researchers generated a bank of CMVSTs from just eight healthy donors, carefully selected based on their HLA profile, to provide broad coverage to a racially and ethnically diverse allogeneic HSCT patient population.
These CMVSTs were administered to treat life-threatening CMV virus-associated disease in allogeneic HSCT recipients. Of note, all infused patients had failed at least seven days of treatment with ganciclovir and/or foscarnet or could not tolerate standard antiviral medications. Of 29 patients screened for study participation, researchers were able to identify a suitable line (minimum two shared HLA antigen threshold) for 28 (96.6%) with a median of 4 shared HLA antigens. Of these, 10 patients with persistent/refractory CMV infections or disease were eligible for treatment and a single infusion of cells produced 3 partial responses and 7 complete responses for a cumulative response rate of 100% (95% CI, 69.2-100%) with no graft versus host disease (GvHD), graft failure or cytokine release syndrome.
CMV infections remain a major cause of morbidity and mortality after allogeneic HSCT, and standard antiviral therapies are associated with significant side effects and development of drug resistant mutants. Center for International Blood and Marrow Transplant Research (CIBMTR) data show that early post-transplant CMV reactivation occurs in over 30% of CMV seropositive HSCT recipients and can result in colitis, retinitis, pneumonitis, and death. Adoptively transferred donor-derived CMV-specific T cells (CMVSTs) can provide an alternative treatment modality with few side effects, but are not widely available due to their patient-specific nature.
AlloVir (formerly ViraCyte), founded in 2013 by researchers at Baylor College of Medicine’s Center for Cell and Gene Therapy, is the leader in the development of novel cell therapies with a focus on restoring natural T-cell immunity against life-threatening virus-associated diseases in patients with severely weakened immune systems. The company’s technology platforms deliver commercially scalable solutions by leveraging off-the-shelf, allogeneic, multi-virus specific T-cells targeting devastating viral pathogens for immunocompromised patients under viral attack. AlloVir’s technology and manufacturing process enables potentially hundreds of patients to be treated with virus-specific T-cells manufactured from a single donor, using a proprietary cell selection strategy to match the company’s bank of third- party donor-derived cell lines to patients.
The company’s lead therapy Viralym-M (ALVR105) is in late-stage clinical development as an allogeneic, off-the-shelf multi-virus specific T-cell therapy targeting six common viral pathogens: BK virus, cytomegalovirus, adenovirus, Epstein-Barr virus, JC virus, and human herpes virus 6. In a positive Phase 2 proof-of-concept study, published in the Journal of Clinical Oncology (Tzannou, JCO, 2017), greater than 90% of patients who failed conventional treatment and received Viralym-M demonstrated a complete or partial clinical response based on predefined criteria, and most exhibited complete elimination of detectable virus in the blood and resolution of major clinical symptoms. AlloVir also is advancing multiple mid- and late-stage clinical trials across its product portfolio.