FDA Approves Papzimeos, First Immunotherapy for Recurrent Respiratory Papillomatosis

The U.S. Food and Drug Administration (FDA) has approved Papzimeos (zopapogene imadenovec-drba), the first-in-class, non-replicating adenoviral vector-based immunotherapy, for the treatment of adult recurrent respiratory papillomatosis (RRP). In a pivotal trial, 51.4% of patients remained surgery-free for 12 months post-treatment. The therapy has demonstrated durable efficacy with minimal safety concerns.

Immunotherapy Tailored for a Viral-Driven Disease

Administered via subcutaneous injection, Papzimeos is a gene-based immunotherapy designed to elicit a targeted immune response against HPV 6 and 11-infected cells—the viral culprits behind recurrent respiratory papillomatosis. By inducing HPV-specific T-cell activation, it offers a disease-modifying alternative to repeated surgical intervention, marking a significant shift from purely mechanical treatments.

“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,” said Dr. Vijay Kumar, Acting Director of the Office of Therapeutic Products in CBER.

The FDA’s approval is based on a single-arm, open-label trial enrolling adult patients with severe disease, defined by the need for at least three surgeries annually. Participants received four injections over 12 weeks following their most recent surgical debulking.

The clinical results were compelling:

51.4% (18 of 35 patients) achieved a complete response, defined as remaining surgery-free for at least one year post-treatment.
Durable responses were observed for up to two years, with efficacy strongly correlated to the induction of HPV 6/11-specific T cells.
The safety profile was favorable, with no dose-limiting toxicities or treatment-related serious adverse events reported.

Papzimeos was granted Breakthrough Therapy designation, Orphan Drug status, and underwent Priority Review, reflecting both the severity of the disease and the drug’s potential to fill a critical therapeutic gap.

“Randomized trials are not always needed to approve medical products and this approval is proof of that philosophy,” said Dr. Vinay Prasad, Director of the FDA’s Center for Biologics Evaluation and Research (CBER). “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.”

A Disease Long Managed by the Scalpel

RRP, caused by persistent infection with human papillomavirus (HPV) types 6 or 11, leads to the growth of benign, yet obstructive tumors primarily in the larynx and upper respiratory tract. Despite its benign nature, RRP exacts a high toll: patients often endure chronic voice disturbances, breathing difficulties, and recurrent airway obstruction. Until now, repeated surgical debulking was the only option to manage symptoms—procedures that carry their own risks and do not address the underlying viral pathology.

Implications for Clinical Practice

For otolaryngologists and infectious disease specialists, the approval of Papzimeos represents an opportunity to shift from palliative surgical management to immunologically targeted therapy. While long-term outcomes and pediatric indications will require further study, the current approval offers immediate benefit to a neglected adult patient population.