FDA Accepts BLA for PRGN-2012 for Recurrent Respiratory Papillomatosis

The US Food and Drug Administration (FDA) has accepted the Biologics License Application for PRGN-2012 (zopapogene imadenovec), an investigational gene therapy for the treatment of adults with recurrent respiratory papillomatosis (RRP).1

Announced by Precigen, Inc., on February 25, 2025, the regulatory agency granted the BLA Priority Review, setting a Prescription Drug User Fee Act (PDUFA) target action date of August 27, 2025, and indicating no plans to hold an advisory committee meeting.

“The priority review designation is a testament to the FDA’s recognition of the significant unmet need for the RRP patient population,” said Helen Sabzevari, PhD, president and chief executive officer of Precigen, in a statement. “RRP patients have never had an FDA-approved therapy, relying instead of repeated surgeries to alleviate the symptoms of RRP without addressing the underlying disease.”

A rare, difficult, lifelong neoplastic disease, RRP affects the upper and lower respiratory tracts and is caused by infection with HPV 6 or HPV 11 which can be fatal. 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. Each RRP surgery is linked to an elevated cumulative risk of laryngeal injury, particularly those requiring ≥5 lifetime surgeries.2

Citing an unmet need for a therapeutic alternative to these life-altering injuries, PRGN-2012, Precigen’s investigational AdenoVerse gene therapy could become the first FDA-approved therapeutic to address RRP in adults. It has been designed to induce an immune response against cells infected with HPV 6 or HPV 11.1

Pivotal Phase 1/2 clinical trial data, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, supported the BLA submission. 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’s primary outcome was the complete response rate or the percentage of individuals who did not require intervention to control RRP in the 12 months following treatment. Upon analysis, 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.

“Treatment with PRGN-2012 has shown significant, durable clinical benefit,” Sabzevari stated.1 We have patients treated with PRGN-2012 who have been surgery-free for more than three years now, bringing hope for an alternative to the cycle of repeated surgeries, which carry immense risk for irreversible damage and significant morbidity.”

Further analysis into safety outcomes revealed the therapy was well-tolerated, with no dose-limiting toxicities. The findings 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

PRGN-2012 has previously received Breakthrough Therapy Designation, Orphan Drug Designation, and an accelerated approval pathway from the FDA, and Orphan Drug Designation from the European Commission.

“We look forward to working with the FDA over the coming months during their BLA review and hope to introduce the first FDA-approved therapeutic option to the RRP patient population, estimated at more than 27,000 adults in the US, later this year,” Sabzevari added.1

References

1. FDA Grants Priority Review to Precigen’s BLA for PRGN-2012 for the treatment of adults with recurrent respiratory papillomatosis with PDUFA target action date set for August 27, 2025. Precigen. February 25, 2025. Accessed February 25, 2025. https://investors.precigen.com/news-releases/news-release-details/fda-grants-priority-review-precigens-bla-prgn-2012-treatment.

2. Rivera GA, Morell F. Laryngeal Papillomas. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562327/

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