Posoleucel for Virus-Associated Hemorrhagic Cystitis Receives Orphan Drug Designation

The FDA has granted orphan drug designation to AlloVir’s posoleucel, an investigational T-cell therapy for the potential treatment of virus-associated hemorrhagic cystitis (HC).¹

Posoleucel is being evaluated in a phase 3, multicenter, double-blind, placebo-controlled study (NCT04390113) that is currently enrolling patients with virus-associated HC following allogeneic hematopoietic stem cell transplant (HSCT).

"This Orphan Drug Designation acknowledges the urgent need for new treatment options for patients who have undergone HSCT and are at risk for developing viral infections and hemorrhagic cystitis," said Ercem Atillasoy, MD, chief regulatory and safety officer, AlloVir, in a statement.¹ "We look forward to working with the FDA and regulators around the globe as we advance this therapy for patients in need."

Posoleucel was previously validated for the treated of HC in the phase 2 CHARMS study (NCT02108522). In the study, over 90% of patients for which previous therapies had failed had a complete or partial response to the therapy. Specifically, most of these patients had no more detectable virus in their blood and had resolved major clinical symptoms. Posoleucel was previously granted regenerative medicine advanced therapy designation from the FDA and orphan medicinal product and priority medicines designations from the EMA for the treatment of HC.

READ MORE: Krabbe Disease Gene Therapy Receives Second Orphan Drug Designation

The allogeneic, off-the-shelf, multi-virus specific T-cell therapy is also under development, in a phase 2 study (NCT04693637) for the prevention of 6 viral pathogens in immunocompromised people including BK virus (BKV), polyomavirus JC virus (JCV), cytomegalovirus (CMV), human herpes virus-6 (HHV-6), Epstein Barr virus (EBV) and adenovirus (AdV). A phase 2 proof-of-concept study (NCT04605484) of posoleucel for the preemptive treatment of BK viremia in adults after kidney transplant is also currently recruiting. 

ALVR109, another allogeneic T-cell therapy by AlloVir, previously showed efficacy against the SARS-CoV-2 virus.² AlloVir presented positive data in September at IDWeek 2021 from a phase 1b trial (NCT04401410) of 4 patients at high-risk for poor outcomes with COVID-19. The 4 patients received a single infusion of ALVR109 at 2 dose levels. All patients experienced clinical improvement following treatment; 3 patients remain well and virus-free while 1 patient experienced a late recurrence of the virus and died 4 weeks after treatment. ALVR109 was well-tolerated save 1 serious adverse event of transient cytokine release syndrome deemed attributable to COVID-19 disease progression.

“The preclinical data presented today underscore the power of AlloVir’s virus-specific T cell therapy platform, demonstrating the speed at which we can identify target antigens, advance these to our manufacturing process and generate highly potent VSTs that are effective against a broad range of SARS-CoV-2 variant strains, including the Delta variant,” co-author Ann Leen, PhD, chief scientific officer, AlloVir, said in a statement at that time.² “These cells are capable of targeting not only spike, including the majority of spike-mutated T cell epitopes present in clinically important variant strains, but also four additional structural and non-structural proteins. This broad immune reactivity minimizes the potential risk of immune escape from our therapy.”

REFERENCES

1. 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
2. Data presented at IDWeek™ 2021 demonstrate that ALVR109, AlloVir’s investigational SARS-CoV-2-specific T cell therapy, is reactive against a broad range of variants, including delta. News release. AlloVir. September 29, 2021.