Long-Term Data Support New Zopapogene Imadenovec Approval for RRP

Updated long-term follow-up data from the pivotal phase 1/2 study of zopapogene imadenovec, that recently led to its approval for the treatment of adult patients with recurrent respiratory papillomatosis (RRP), continue to demonstrate long term responses.1,2

The data were presented at the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF) 2025 Annual Meeting & OTO EXPO, held in Indianapolis, Indiana, on October 11-14, 2025.

"The updated durability data reinforce that PAPZIMEOS is not only a medical breakthrough but a transformative therapy for the RRP community," Helen Sabzevari, PhD, President and CEO of Precigen, said in a statement.1 "For patients and their families, sustained responses mean freedom from the relentless cycle of repeat surgeries, reduction in the risk of surgical damage, and the possibility to improve quality of life. For physicians, it provides confidence in a safe and effective therapy that addresses the root cause of disease. And for the healthcare system, durable responses translate into fewer procedures, reduced complications, and lower long-term burden of care. This is precisely the type of impact we envisioned when we set out to develop what would become the first FDA-approved therapy for adults with RRP."

The new data demonstrated that as of September 19, 2025, with a median duration of 36 months of follow-up (range, 27-37), 15 out of the 18 complete responders (83%) in the pivotal study continuing to have ongoing complete responses. The median duration of complete response has yet to be reached in the study and no new safety events were observed during the follow-up. Compared to pretreatment, 86% of patients had a decreased number of surgeries in year 1, 91% in year 2, and 95% in year 3.1

Zopapogene imadenovec was approved in August 2025 under the name Papzimeos.2 Data from the pivotal study supporting the approval 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

“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.2 “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 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.3

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

“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.2

References

1. Precigen Announces Long-Term Follow-Up Results Highlighting Ongoing Durable Complete Responses after Treatment with PAPZIMEOS, the First and Only FDA-approved Therapy for Adults with Recurrent Respiratory Papillomatosis. News release. Precigen. October 13, 2025. https://www.prnewswire.com/news-releases/precigen-announces-long-term-follow-up-results-highlighting-ongoing-durable-complete-responses-after-treatment-with-papzimeos-the-first-and-only-fda-approved-therapy-for-adults-with-recurrent-respiratory-papillomatosis-302581497.html

2. 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

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