The FDA has approved zopapogene imadenovec-drba (Papzimeos) as the first-of-its-kind non-replicating adenoviral vector-based immunotherapy for treating adult patients with recurrent respiratory papillomatosis (RRP), marking a significant milestone for patients with this rare and challenging condition.
The approval, announced on August 14, comes ahead of the original Prescription Drug User Fee Act (PDUFA) target action date of August 27, 2025, following the FDA's acceptance of Precigen's biologics license application in February.
Clinical Trial Results Drive Approval
The FDA's decision was supported by findings from a pivotal Phase 1/2 clinical trial that demonstrated significant clinical activity. The single-center, single-arm trial evaluated 35 adults with RRP who received the recommended Phase 2 dose of 5×10¹¹ particle units administered on Days 1, 15, 43, and 85.
The trial met its primary outcome with 51% of patients achieving a complete response (95% CI, 34–69). Additionally, at least 85% of patients experienced a decrease in surgical intervention one year after completing treatment with zopapogene imadenovec-drba.
Safety Profile and Tolerability
The therapy demonstrated a well-tolerated safety profile throughout the clinical trial. No dose-limiting toxicities were observed, and the trial reported no treatment-related adverse events greater than Grade 2. The most common adverse events were Grades 1–2 injection site reactions (97%), fatigue (80%), chills (71%), and fever (69%).
Addressing Unmet Medical Need
RRP is a rare, difficult, lifelong neoplastic disease affecting the upper and lower respiratory tracts, caused by infection with HPV 6 or HPV 11. The condition leads to the growth of benign tumors in the respiratory tract, generally in the larynx. Without a cure for RRP, patients face a cycle of recurrence requiring repeated surgeries throughout their lifetime, with some patients needing hundreds of surgical interventions. The disease can be fatal and is associated with significant morbidity.
"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 Vijay Kumar, MD, Acting Director of the Office of Therapeutic Products in the FDA's Center for Biologics Evaluation and Research (CBER).
Regulatory Perspective
The approval highlights the FDA's flexible approach to clinical evidence requirements for rare diseases. "Randomized trials are not always needed to approve medical products and this approval is proof of that philosophy," stated Vinay Prasad, MD, MPH, Director of 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."
The clinical trial data supporting this approval were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrating the therapy's potential to address a significant unmet medical need in the treatment of this rare condition.
