INOVIO's investigational DNA medicine INO-3107 has demonstrated sustained and improving long-term clinical benefits in patients with Recurrent Respiratory Papillomatosis (RRP), according to new data published in The Laryngoscope. The retrospective study of 28 patients showed that clinical responses continued to improve over time, with the overall response rate increasing from 72% in Year 1 to 86% in Year 2.
Sustained Clinical Improvement Over Time
The retrospective trial, which followed patients for a median of 2.8 years after initial treatment, revealed progressive improvements in key clinical outcomes. The Complete Response rate nearly doubled from 28% in Year 1 to 50% in Year 2, meaning half of all patients required no surgeries at all during the second year following treatment.
Most significantly, the mean number of surgeries needed to control RRP continued to decline over time. Patients required an average of 4.1 surgeries per year before treatment, which dropped to 1.7 surgeries in Year 1 and further decreased to 0.9 surgeries in Year 2 - representing a 78% reduction from pre-treatment levels.
"The most important takeaway from this data is that the majority of patients experienced a reduction in surgeries following initial treatment with INO-3107, and almost all of those patients maintained or improved their response 2 years after initial treatment," said Dr. Aaron Friedman, Associate Professor of Clinical Otolaryngology, Head and Neck Surgery at University of Cincinnati Medical Center and principal investigator on the trial.
Mechanism and Treatment Approach
INO-3107 is designed to elicit an antigen-specific T cell response against both HPV-6 and HPV-11 proteins, the primary causes of RRP. These targeted T cells seek out and kill HPV-infected cells, potentially preventing or slowing the growth of new papillomas. The treatment generated strong immune responses in the trial, inducing activated CD4 and CD8 T cells with lytic potential, with T cell responses observed at Week 52, indicating persistent cellular memory response.
The DNA medicine is delivered using INOVIO's proprietary CELLECTRA device, which optimizes delivery without requiring chemical adjuvants or lipid nanoparticles. Unlike viral vector platforms, DNA medicines maintain T cell response and overall efficacy without being affected by anti-vector immunity.
Safety Profile and Regulatory Status
INO-3107 was well tolerated throughout the extended follow-up period, with no serious adverse events or long-term safety concerns identified. Trial participants experienced mostly low-grade treatment-emergent adverse effects such as injection site pain and fatigue.
The FDA has granted INO-3107 both Orphan Drug and Breakthrough Therapy designations and has advised INOVIO that it can submit a biologics license application under the FDA's accelerated approval program using data from the completed Phase 1/2 trial. The European Commission has also granted Orphan Drug designation, and INOVIO has CE-marked its CELLECTRA delivery device in the EU.
Clinical Significance for RRP Patients
RRP is a debilitating rare disease characterized by wart-like growths in the respiratory tract that can cause severe airway obstruction and significantly affect quality of life by limiting patients' ability to speak effectively. Surgery to remove papillomas is the current standard of care, but the growths often recur, requiring repeated procedures that pose risks of permanent vocal cord damage.
"Understanding how much every single surgery matters to patients, it is compelling to see the vast majority of patients experienced significant benefit from treatment with INO-3107, resulting in a reduction in the number of surgeries required to control their disease — a benefit that continued and often improved over time," said Dr. Jacqueline Shea, INOVIO's President and Chief Executive Officer.
The most widely cited U.S. epidemiology data estimates 14,000 active cases and approximately 1.8 per 100,000 new cases of RRP in adults annually. INOVIO's market research indicates that even a reduction of one surgery matters significantly to patients due to the associated risks, costs, and quality of life impacts.
