Zopapogene imadenovec-drba, a novel non-replicating adenoviral vector-based immunotherapy: Effects on complete and durable responses in recurrent respiratory papillomatosis pivotal trial.

6104 Background: Recurrent respiratory papillomatosis (RRP) is a rare, neoplastic disorder caused by chronic human papillomavirus (HPV) type 6 or 11 infection. Significant morbidity can occur due to airway obstruction and transformation into malignant cancer. Repeat surgical debulking has historically been the most common treatment for RRP symptom management. Zopapogene imadenovec-drba (zopa), a novel adenoviral vector-based immunotherapy, is the first and only FDA-approved treatment for adults with RRP. Zopa is now recommended as the first-line treatment for adults with RRP in an RRP Foundation position statement authored by 16 key opinion leaders (Best et al. Laryngoscope 2026). Methods: The pivotal trial (NCT04724980) evaluated zopa in patients with RRP requiring ≥3 clinically indicated interventions 12 months (m) prior to treatment. 12m follow-up data was reported and demonstrated that 4 subcutaneous injections of zopa (5x10 11 particle units per injection; n=35) were well-tolerated, with no serious adverse events, no grade >2 treatment-related adverse events, and no early treatment discontinuations. The most common adverse events were injection-site reaction, fatigue, chills, fever, and myalgia. Robust efficacy was observed following zopa treatment with 51% (34 to 69; 95% CI) of patients achieving a complete response (CR), defined as no requirement for interventions in the 12m following treatment, and 86% (30/35) of patients experiencing a decrease in interventions in the year following treatment as compared to the year prior to treatment. Here we present data up to 51m of follow-up. Results: As of December 15, 2025, 83% (15/18) of patients who achieved a CR at 12m remain in CR with no recurrence of papilloma requiring surgical or medical intervention. The median duration of follow-up for patients in CR was 36m (range: 30-51m), with 3 patients having a response lasting more than 4 years. No new safety events were observed during long-term follow-up. Conclusions: Zopa treatment demonstrated significant clinical benefit with the vast majority of CR patients experiencing ongoing durable complete responses for up to 4 years with excellent long-term safety. Updated follow-up results for all patients achieving CR will be available at the time of presentation. Clinical trial information: NCT04724980 .