Breaking the Surgery Cycle in RRP With First Immunotherapy, with Simon Best, MD

The FDA the first immunotherapy for treating adults with recurrent respiratory papillomatosis (RRP), zopapogene imadenovec-drba, to be marketed as Papzimeos, on August 14. The therapy is the first-of-its-kind non-replicating adenoviral vector-based immunotherapy.1

RRP is caused by infection with HPV 6 or HPV 11 and is a rare, difficult, lifelong neoplastic disease that affects the upper and lower respiratory tracts. Prior to this approval, no disease-modifying therapies were available and patients often require repeated surgeries in cycles of recurrence, all of which are associated with significant mortality.

The obvious unmet need in RRP led to the FDA approving zopapogene imadenovec (previously known as PRGN-2012) after safety and efficacy were demonstrated in just 1 single-center, single-arm Phase 1/2 clinical trial. Data from the trial were presented at the 2024 American Society of Clinical Oncology Annual Meeting and were from 35 adults with RRP who received the recommended Phase 2 dose of 5×1011 particle units at Days 1, 15, 43, and 85.2

The trial met its primary outcome, with 51% of patients achieving a complete response (95% CI, 34–69) and ≥85% of patients experiencing a decrease in surgical intervention a year after completing PRGN-2012 treatment. The therapy was also well-tolerated, with no dose-limiting toxicities. The trial reported no treatment-related adverse events greater than Grade 2, with most being Grades 1–2 injection site reactions (97%), fatigue (80%), chills (71%), and fever (69%).2

HCPLive spoke with Simon Best, MD, Associate Professor of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, to learn more about how zopapogene imadenovec might transform outcomes for adults with RRP.

“It's just an endless cycle of surgery and regrowth, surgery and regrowth. To have something that can medically, immunologically, break that cycle, and remove the infection, that's the hope, and that's what we're going to hopefully achieve with these new medications,” Best said.

References

1. Johnson V. Zopapogene Imadenovec First Immunotherapy Approved for Recurrent Respiratory Papillomatosis. Article. August 14, 2025. https://www.hcplive.com/view/zopapogene-imadenovec-first-immunotherapy-approved-for-recurrent-respiratory-papillomatosis

2. Norberg SM, Valdez J, Napier S, et al. PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: a pivotal phase 1/2 clinical trial. Lancet Respir Med. Published online January 21, 2025. doi:10.1016/S2213-2600(24)00368-0