INOVIO's RRP Drug Enters FDA Review Amid Accelerated Approval Questions

PLYMOUTH MEETING, Pa. – December 29, 2025 – Biotechnology firm INOVIO announced today that the U.S. Food and Drug Administration (FDA) has accepted its application for INO-3107, a novel DNA medicine for adults with Recurrent Respiratory Papillomatosis (RRP), a rare and debilitating disease. While the acceptance marks a significant step forward, the agency has simultaneously raised a critical question about the company's chosen regulatory path, creating a pivotal challenge for the treatment's journey to market.

The FDA has set a target action date of October 30, 2026, under the Prescription Drug User Fee Act (PDUFA), by which it will make its decision. Notably, the agency has indicated it does not currently plan to convene an advisory committee meeting, a step often taken for novel therapies or complex applications. However, in its acceptance letter, the FDA flagged a "potential review issue," stating its preliminary view that INOVIO has not yet provided sufficient information to justify its eligibility for the accelerated approval pathway, a program designed to speed promising drugs for serious conditions to patients.

A Lifeline for a Relentless Disease

Recurrent Respiratory Papillomatosis is a rare condition caused by human papillomavirus (HPV) types 6 and 11, leading to the growth of non-cancerous, wart-like tumors called papillomas in the respiratory tract. These growths, while typically benign, can cause severe and sometimes life-threatening airway obstruction. For patients, the disease profoundly impacts quality of life, most notably by affecting the larynx, or voice box, which can lead to a weak, hoarse voice or even the complete loss of speech.

The current standard of care involves repeated surgeries to remove the papillomas and keep the airway clear. Patients often endure dozens, and in some cases hundreds, of procedures over their lifetime. Each surgery carries inherent risks, including potential anesthesia complications and, most critically, the risk of permanent scarring of the vocal cords, which can worsen voice problems. The relentless cycle of tumor regrowth and surgical intervention creates a significant physical, emotional, and financial burden for those living with RRP. It is this high unmet medical need for a non-surgical option that forms the foundation of INOVIO's development program.

"We believe there remains a critical unmet need among patients diagnosed with this rare and devastating disease and that every RRP patient deserves access to a non-surgical treatment option that can work for them," stated Dr. Jacqueline Shea, INOVIO's President and Chief Executive Officer, in a press release. "Every surgery matters to patients and we look forward to continuing to collaborate with the FDA during the BLA review cycle."

The Promise of a DNA-Based Approach

Unlike surgery, which only addresses the existing tumors, INO-3107 is designed to target the root cause of the disease. It is a DNA medicine that instructs the patient's own body to generate a targeted T-cell immune response against the HPV-6 and HPV-11 viruses. These specialized T-cells are intended to seek out and destroy virus-infected cells, thereby preventing or slowing the growth of new papillomas.

The Biologics License Application (BLA) is supported by compelling data from a Phase 1/2 clinical trial involving 32 adult patients who had required at least two surgeries in the year prior to the study. The results, published in peer-reviewed journals Nature Communications and The Laryngoscope, demonstrated a significant clinical benefit. In the first year after treatment, 72% of patients experienced a reduction of 50% to 100% in the number of required surgical interventions compared to the previous year. Patients in the trial had a median of four surgeries in the year before receiving INO-3107.

Perhaps more impressively, long-term follow-up data showed the treatment's effect was durable. A retrospective study of the original participants found that in the second year after the initial dosing—and with no additional treatment—the number of patients seeing a clinical benefit increased, with 86% of evaluable patients requiring fewer surgeries. Remarkably, half of those patients required no surgeries at all during that second year. The treatment was also found to be well-tolerated, with most reported side effects being low-grade, such as injection site pain and fatigue.

Navigating the Regulatory Gauntlet

The central challenge now facing INOVIO is the FDA's skepticism regarding the accelerated approval pathway. This pathway allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint—a marker thought to predict clinical benefit. In this case, the reduction in the need for surgery is the proposed endpoint. If granted, accelerated approval would allow INO-3107 to reach patients sooner, though the company would likely be required to conduct further studies to confirm the drug's long-term benefit.

The FDA's preliminary conclusion that INOVIO has not submitted adequate justification for this pathway puts the company in a difficult position. INOVIO has stated its firm belief that INO-3107 provides a "meaningful therapeutic benefit over existing treatments" and plans to request a meeting with the FDA to address the agency's concerns. Complicating matters, the company has also stated it is not currently planning to seek approval under the traditional, typically longer, pathway.

This strategy raises the stakes for the upcoming discussions with the FDA. Success in persuading the agency of the drug's eligibility for accelerated approval is now paramount. The drug's existing Breakthrough Therapy and Orphan Drug designations from the FDA underscore the agency's recognition of RRP's seriousness and the potential for INO-3107 to provide a substantial improvement over available therapy. Similar designations from European and UK regulators, including the Innovation Passport in the United Kingdom, further highlight the international interest in the therapy.

As the October 2026 PDUFA date approaches, the focus for INOVIO, its investors, and the RRP patient community will be on the outcome of the company's engagement with the FDA. The path forward will determine how soon this promising, non-surgical DNA medicine could become a reality for patients long caught in a cycle of repeated surgeries.