FDA Grants RMAT Designation to AlloVir’s Posoleucel for Adenovirus Infections Post-Allogeneic Stem Cell Transplantation
January 5, 2022
The U.S. Food and Drug Administration granted AlloVir’s lead multi-virus specific T cell therapy, posoleucel, Regenerative Medicine Advanced Therapy designation for the treatment of adenovirus infection following allogeneic hematopoietic stem cell transplant.
The designation is based on positive results from the phase 2 CHARMS study and recognizes the potential for posoleucel to address the unmet medical need posed by adenovirus infection (AdV), a potentially life-threatening condition with no approved treatment options. RMAT designation enables early interactions with the FDA to discuss clinical trial design and other actions to expedite development and review. The FDA previously granted RMAT designation to posoleucel for the treatment of hemorrhagic cystitis caused by BK virus in adults and children following allogeneic hematopoietic stem cell transplant (allo-HCT).
Upper respiratory tract infections due to hMPV, influenza, PIV and RSV are detected in up to 40 percent of allo-HCT patients. In approximately half of these patients, these viral infections progress to lower respiratory tract infections and present a 20-45% mortality rate. There are no approved treatments or vaccines for hMPV and PIV, and there is no vaccine for RSV; treatments for RSV and influenza have limitations.
AdV is a potentially life-threatening viral infection that has no approved treatments. AdV viremia occurs in approximately one third (32 percent) of pediatric allo-HCT patients and 6 percent of adult allo-HCT patients. The spectrum of AdV-associated disease in HCT patients ranges from mild gastroenteric or respiratory symptoms to pneumonia, hepatitis, severe hemorrhagic enteritis or cystitis, multi-organ failure or death. The current standard of care is off-label use of an antiviral that has demonstrated limited efficacy and significant toxicity.
AlloVir’s lead product, posoleucel, 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 herpes virus-6 (HHV-6) and JC virus (JCV). In the positive phase 2, proof-of-concept CHARMS study, more than 90 percent 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.
A phase 3 registrational study of posoleucel for the treatment of AdV viremia is now open and enrolling pediatric and adult patients following allo-HCT. This study is the second phase 3 registrational study of posoleucel, following the initiation of the phase 3 study for the treatment of virus-associated HC last year.
Separately, the company also announced the initiation of a phase 1/2 clinical trial of ALVR106, its investigational, allogeneic, off-the-shelf, multi-VST therapy for the treatment of infections caused by human metapneumovirus (hMPV), influenza, parainfluenza virus (PIV) and respiratory syncytial virus (RSV). This trial extends AlloVir’s VST platform to tackle respiratory viruses that pose a considerable risk for autologous and allo-HCT patients.
“The initiation of these posoleucel and ALVR106 studies represents important progress in our effort to bring forward much needed treatment options for immunocompromised patients,” said Richard Riese, senior vice president of clinical research for AlloVir. “These investigational multi-VST therapies aim to restore immunity against viruses that, if left untreated, can have devastating consequences. We look forward to working with study investigators to enroll these studies and demonstrate the potential for VST therapy in areas of urgent unmet need.”
Author: Rare Daily Staff
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