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Virus-Specific T-Cell Therapy Makes Headway in Virus Prevention After Allo-HCT

Several phase 3 trials for AlloVir’s posoleucel are expected to complete enrollment in 2023.

AlloVir’s posoleucel (ALVR105, formerly Viralym-M), an investigational virus-specific T-cell (VST) therapy currently under evaluation across several clinical trials for multiple indications, is on track to complete enrollment in several phase 3 trials by the end of 2023 and has shown promising safety and efficacy in preventing common viruses that infect patients who have recently received allogeneic hematopoietic cell transplants (allo-HCTs) in a phase 2 study.1

Final results from the phase 2 trial (NCT04693637) evaluating posoleucel for multivirus prevention after allo-HCT were reported at the 64th American Society of Hematology (ASH) Annual Meeting, held December 10-12, 2022, in New Orleans, Louisiana. Patients who received posoleucel in this trial showed rates of clinically significant infection which were lower than expected for the 6 viruses the therapy was being evaluated for the prevention of, which included adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and JC virus (JCV). AlloVir additionally reported that the therapy was generally safe and well-tolerated in these patients during repeat dosing.

A phase 3 clinical trial (NCT05305040) evaluating posoleucel for the same indication is now recruiting patients at locations in the United States, Europe, Asia, Australia, and Canada. The trial is open to patients aged 1 year and older who are within 15 to 42 days of having received their first allo-HCT and have achieved clinical engraftment, with no known or suspected disease from the 6 viruses posoleucel is intended to prevent. AlloVir expects that enrollment will be completed by the end of the year and that topline data will be announced in the middle of next year.

“The positive posoleucel phase 2 data we reported in 2022 and the enthusiasm we are seeing from transplant centers give us further confidence in our phase 3 strategy for posoleucel and our ability to execute on our trials in 2023,” Diana Brainard, MD, chief executive officer, AlloVir, said in a statement regarding the news.1 “Our phase 2 multi-virus prevention study data underscore the potential for posoleucel to be transformative for allo-HCT patients by substantially reducing clinically significant infections from 6 viruses that are devastating for this vulnerable population. Viral infections are a leading cause of non-relapse mortality, generate substantial healthcare expenditures, exact a significant emotional burden on patients and their caregivers, and unfortunately most viruses targeted by posoleucel currently have no preventive therapies.”

In addition to the multi-virus prevention trials, posoleucel is also being evaluated for the treatment of already-existing viral infections in several additional clinical trials. A phase 3 registrational study (NCT04390113) assessing posoleucel for the treatment of virus-associated hemorrhagic cystitis (vHC) is currently recruiting patients aged 1 day and older who received aHCT between 21 days and 1 year (inclusive) before random assignment, achieved myeloid engraftment, and have been diagnosed with HC. Another phase 3 registrational trial (NCT05179057) is evaluating posoleucel for the treatment of AdV infection. It is currently recruiting patients aged 1 year and older who received allo-HCT at least 21 days before random assignment and who have demonstrated engraftment and shown evidence of AdV infection according to study criteria. Both of these phase 3 trials are also expected to complete enrollment by the end of the year, with topline data expected in 2024.

A phase 2 clinical trial (NCT04605484) assessing posoleucel for the treatment of BK viremia in patients who have received kidney transplant is also ongoing. The trial recruited patients aged 18 years and older who had received a kidney transplant at least 28 days before enrollment and had high or low levels of BK virus in their blood. AlloVir expects to report final topline data from this study before the end of the first quarter of this year.

Posoleucel previously received orphan drug designation from the FDA for the treatment of vHC in October of 2021 and regenerative medicine advanced therapy designation for multi-virus prevention in April of2022.3 In addition to posoleucel, AlloVir has several early clinical and preclinical programs in its pipeline, including ALVR106, an allogeneic multi-VST therapy being evaluated for the treatment of respiratory syncytial virus (RSV), human metapneumovirus, parainfluenza, and influenza in a phase 1b/2 trial (NCT04933968).

REFERENCES
1. AlloVir announces plans to complete enrollment in three phase 3 posoleucel studies in 2023. News release. AlloVir, Inc. January 9, 2023. https://ir.allovir.com/news-releases/news-release-details/allovir-announces-plans-complete-enrollment-three-phase-3 
2. FDA grants orphan drug designation (ODD) to AlloVir’s posoleucel, an allogeneic, off-the-shelf, multi-virus specific T-cell therapy, for the treatment of virus-associated hemorrhagic cystitis. News release. AlloVir. October 4, 2021. https://ir.allovir.com/news-releases/news-release-details/fda-grants-orphan-drug-designation-odd-allovirs-posoleucel 
3. FDA grants regenerative medicine advanced therapy (RMAT) designation to AlloVir’s posoleucel 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