Zopapogene Imadenovec First Immunotherapy Approved for Recurrent Respiratory Papillomatosis

As of today, August 14, the FDA has approved zopapogene imadenovec-drba for the treatment of adult patients with recurrent respiratory papillomatosis (RRP) as the first-of-its-kind non-replicating adenoviral vector-based immunotherapy, under the name Papzimeos.1

“Randomized trials are not always needed to approve medical products and this approval is proof of that philosophy,” Vinay Prasad, MD, MPH, Director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in a statement.1 “The FDA will always demand the correct clinical study for the specific medical product and disease. Our requirements for products given to tens of millions of healthy people will be different than products given to at most hundreds or thousands of patients with unique diseases.”

The FDA previously accepted Precigne's biologics license application for the therapy in February 25 and set a Prescription Drug User Fee Act (PDUFA) target action date of August 27, 2025.2

“This approval has the potential to transform the treatment landscape for RRP and offer lasting relief for patients who previously faced repeated surgeries to control symptoms of their disease,” Vijay Kumar, MD, Acting Director of the Office of Therapeutic Products in CBER, added.1

RRP is a rare, difficult, lifelong neoplastic disease that affects the upper and lower respiratory tracts and is caused by infection with HPV 6 or HPV 11. Without a cure for RRP, repeated surgeries are associated with significant morbidity, as the cycle of recurrence leads to patients requiring hundreds of lifetime surgeries and the disease can be fatal.

The approval is support by findings from a pivotal Phase 1/2 clinical trial data, data from which were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The single-center, single-arm, Phase 1/2 trial evaluated the safety and clinical activity of PRGN-2012 in 35 adults with RRP who received the recommended Phase 2 dose of 5×1011 particle units at Days 1, 15, 43, and 85.3

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.

Zopapogene imadenovec-drba also had a well-tolerated safety profile, 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%).3

REFERENCES

1. FDA Approves First Immunotherapy for Recurrent Respiratory Papillomatosis. News release. FDA. August 14, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-immunotherapy-recurrent-respiratory-papillomatosis

2. Iapoce C. FDA Accepts BLA for PRGN-2012 for Recurrent Respiratory Papillomatosis. HCPLive. February 25, 2025. https://www.hcplive.com/view/fda-accepts-bla-for-prgn-2012-for-recurrent-respiratory-papillomatosis

3. 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