FDA Approves Zopapogene Imadenovec for Recurrent Respiratory Papillomatosis

The FDA approved zopapogene imadenovec-drba (Papzimeos; Precigen) as the first and only therapy for recurrent respiratory papillomatosis (RRP) in adult patients, according to a press release.¹

The root cause of RRP, a rare and potentially life-threatening upper- and lower-respiratory tract disease, is human papillomavirus (HPV). Zopapogene imadenovec, a nonreplicating adenoviral vector-based immunotherapy, expresses a fusion antigen made up of selected regions of HPV types 6 and 11 proteins. It is administered via 4 subcutaneous injections over a 12-week interval.

"For more than a century, since RRP was first recognized as a distinct disease, patients have had to rely on repeated surgeries to manage this relentless condition," Helen Sabzevari, PhD, president and CEO of Precigen, said in a statement.¹ "Today marks a historic turning point. With the landmark FDA approval of [zopapogene imadenovec] and broad label, all adult RRP patients are now eligible for access to the first and only approved therapy that targets the root cause of the disease."

Zopapogene imadenovec, a nonreplicating adenoviral vector-based immunotherapy, expresses a fusion antigen made up of selected regions of human papillomavirus (HPV) types 6 and 11 proteins. | Image Credit: aznan - stock.adobe.com

Zopapogene imadenovec's full FDA approval was based on data from an open-label, single-arm, pivotal study (NCT04724980), which met its primary safety end point and prespecified efficacy end point.¹ Of 35 patients treated at the recommended phase 2 dose (5x10¹¹ particle units), 18 (51%) experienced a complete response (CR; 95% CI, 34-69). The median duration of CR was not yet reached.²

The most common adverse events were grade 1 or 2 injection site reaction (97%), fatigue (80%), chills (71%), and fever (69%).

"This long-awaited FDA approval represents a momentous milestone for the RRP community," Kim McClellan, president of the Recurrent Respiratory Papillomatosis Foundation, said.¹ "For the first time, adult patients with RRP have access to an FDA-approved therapy that offers the potential to reduce—or even eliminate—endless repeated surgeries. This breakthrough brings long-overdue hope to patients and families who have endured so much. We are deeply grateful to the teams at Precigen and the NIH, and above all, to the patients and caregivers whose courage, advocacy, and perseverance have made this historic moment possible."

RRP is rare and debilitating and can lead to severe voice disturbance, a compromised airway, and recurrent pneumonias.

Prior to the new approval, treatment for RRP has mainly entailed repeated surgical excision, which carries a significant burden for patients and the health system and is associated with significant morbidity.¹ Previous research found that in the first 5 years of diagnosis, the average number of surgeries is 5.1 per year.³ By 15 years after diagnosis, the average number of surgeries is 0.1 per year. RRP is therefore expensive to treat, with an estimated cost of nearly $200,000 over a patient’s lifetime, not including drug treatment. Roughly 95% of these costs are related to surgeries.

Surgical excision does not aim to eradicate RRP completely but to preserve patients’ voice quality and keep the airway unobstructed. Extensive excision of papilloma from areas not contributing to relief of airway and voice manifestations has not been found to reduce recurrence. On the other hand, more aggressive resection has been linked with higher HPV expression in nearby infected cells, meaning excessive resection may be counterproductive.

In approximately 20% of patients, surgery alone is not enough to control RRP. While specific indications are not well described, adjuvant therapy is typically considered for patients receiving more than 3 or 4 surgeries per year.

References

1. Precigen announces full FDA approval of Papzimeos (zopapogene imadenovec-drba), the first and only approved therapy for the treatment of adults with recurrent respiratory papillomatosis. News release. Precigen. August 15, 2025. Accessed August 19, 2025. https://investors.precigen.com/news-releases/news-release-details/precigen-announces-full-fda-approval-papzimeos-zopapogene

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 Resp Med. 2025;13(4):318-26. doi:10.1016/S2213-2600(24)00368-0

3. Ivancic R, Iqbal H, deSilva B, Pan Q, Matrka L. Current and future management of recurrent respiratory papillomatosis. Laryngoscope Investig Otolaryngol. 2018;3(1):22-34. doi:10.1002/lio2.132