Clinical Progress and Evaluation Criteria

The NCT05797246 trial, led by the U.S. National Cancer Institute (NCI), is a single-arm Phase 2 study evaluating the effectiveness of intravenous bevacizumab in reducing surgical burden in adult patients with recurrent respiratory papillomatosis (RRP). As of May 2026, the trial status is 'Active, not recruiting,' with enrollment completed and follow-up ongoing. The primary completion is scheduled for 2027, and the overall study end date is set for 2029. The primary endpoint is the proportion of participants with an increased average interval between surgeries during treatment compared to the 12 months before treatment, designed to directly assess the reduction in surgical burden rather than tumor size.

Dosing Strategy and Mechanism of Action

Participants receive a total of 11 bevacizumab infusions following laryngeal papilloma removal surgery, with the first three doses administered every three weeks and the subsequent eight doses every six weeks. Avastin (bevacizumab), developed by Genentech and marketed by Roche, is a vascular endothelial growth factor-A (VEGF-A) neutralizing monoclonal antibody first approved by the FDA on February 26, 2004, for metastatic colorectal cancer. The drug is being repurposed to target the high VEGF expression and vascular dependency of RRP lesions to inhibit papilloma regrowth, and its use for RRP is considered off-label.

The Treatment Landscape Has Already Changed

Repetitive laser and microdebridement surgeries remain the foundation for symptom control but do not eliminate the underlying HPV-6/11 infection and leave risks of vocal cord scarring and airway damage. Precigen (PGEN)'s Papzimeos (zolpidemvir-drba), a non-replicating adenovirus immunotherapy targeting HPV-6/11 proteins, was fully approved by the FDA on August 14, 2025, as the first treatment for adult RRP. In pivotal trials, 51.4% (18 out of 35) of adults who previously required surgery more than three times a year achieved complete response with no surgeries needed for 12 months post-treatment, and it is now established as the first-line drug therapy for adult patients in the U.S.

Competitive Landscape and Market Implications

Bevacizumab is recommended as a second-line drug therapy for adults seeking continued disease control after Papzimeos non-response, competing with existing surgical interventions, intralesional therapies such as cidofovir and bevacizumab, Keytruda (pembrolizumab, PD-1), Lenvima (lenvatinib, VEGFR), and INOVIO (INO)'s HPV-6/11 DNA immunotherapy INO-3107. According to third-party estimates, the seven major RRP treatment markets were valued at USD 10.26 million in 2023, but Precigen estimates a global peak sales opportunity of USD 2 billion for Papzimeos, highlighting the market revaluation following the introduction of approved therapies. Therefore, this Phase 2 trial will serve as critical evidence to determine whether bevacizumab, with its low-cost biosimilar accessibility and high disease suppression potential, can capture the second-line market after the approved immunotherapy.