INO-3107 Immunotherapy Shows Benefit in Recurrent Respiratory Papillomatosis

INO-3107 immunotherapy was well tolerated and provided a continued clinical effect against HPV-6 and 11 and reduced the surgical burden in recurrent respiratory papillomatosis (RRP) in a 1-year study.1

"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," principal investigator Aaron Friedman, MD, Associate Professor of Clinical Otolaryngology, Head and Neck Surgery, University of Cincinnati Medical Center, said in a statement.2 "With this continued improvement in clinical effect, we believe INO-3107 has the potential to change the trajectory of a patient's disease and set a new standard of care for the RRP community."

The new findings were from the retrospective, observational RRP-002 extension study that followed patients enrolled in the 52-week RRP-001 study with moderate to severe juvenile or adult-onset RRP who had undergone ≥ 2 surgical interventions in the year preceding dosing. Participants underwent surgical debulking within 14 days prior to initial dosing and then received INO-3107 on Day 0, Weeks 3, 6, and 9 in RRP-001. Investigators in RRP-002 assessed the frequency of surgical interventions and alternative medication use, as well as the incidence of serious adverse events (SAEs) reported.

RRP-002 included 28 participants of the original 32 from RRP-001 that had a median follow-up time of 1.8 years (range, 1.2–2.4 years) for a total median assessment time of 2.8 years (range, 1.0–3.5 years). Investigators did not observe any SAEs or long-term safety concerns. Friedman and colleagues found that the mean number of surgeries was reduced from 4.1 in the pre-treatment period to 1.7 in the first year post treatment to 0.9 in the second year. The complete response rate of 0 surgeries per year increased from 28% (n = 9/32) in Year 1 to 50% (14/28) in Year 2.1

"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," Jacqueline Shea, INOVIO's President and Chief Executive Officer, added.2 "The sustained reduction in surgery following treatment with INO-3107 demonstrated here is central to our belief that INO-3107 could become the preferred product on the market, if approved."

The data follows the recent United States Food and Drug Administration (FDA) approval of Precigen’s zopapogene imadenovec-drba, as the first-of-its-kind non-replicating adenoviral vector-based immunotherapy for treating RRP. The approval was supported by findings from a pivotal Phase 1/2 clinical trial data, data from which were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The single-center, single-arm, Phase 1/2 trial evaluated the safety and clinical activity of PRGN-2012 in 35 adults with RRP who received the recommended Phase 2 dose of 5×1011 particle units at Days 1, 15, 43, and 85. The trial met its primary outcome, with 51% of patients achieving a complete response (95% CI, 34–69) and ≥85% of patients experiencing a decrease in surgical intervention a year after completing PRGN-2012 treatment.3

“Randomized trials are not always needed to approve medical products and this approval is proof of that philosophy,” Vinay Prasad, MD, MPH, Director of the FDA’s Center for Biologics Evaluation and Research (CBER), said in a statement.3 “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.”

References

1. Amin MR, Belafsky PC, Best SR, et al. DNA Immunotherapy (INO-3107) Results in Long-Term Surgery Reduction in RRP. Laryngoscope. Published online August 9, 2025. doi:10.1002/lary.32416

2. Data Published in The Laryngoscope shows INO-3107 Resulted in Long-Term Surgery Reduction in Recurrent Respiratory Papillomatosis (RRP). News release. Inovio. August 11, 2025. https://www.prnewswire.com/news-releases/data-published-in-the-laryngoscope-shows-ino-3107-resulted-in-long-term-surgery-reduction-in-recurrent-respiratory-papillomatosis-rrp-302526066.html

3. FDA Approves First Immunotherapy for Recurrent Respiratory Papillomatosis. News release. FDA. August 14, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-immunotherapy-recurrent-respiratory-papillomatosis