INOVIO's Hopeful RRP Drug Faces FDA Accelerated Approval Scrutiny

PLYMOUTH MEETING, PA – December 29, 2025 – Biotechnology company INOVIO announced today that the U.S. Food and Drug Administration (FDA) has accepted its application for INO-3107, a novel DNA medicine for a rare and debilitating throat disease. While the acceptance marks a significant step forward, the news was tempered by a critical regulatory challenge: the FDA has expressed doubts about the drug's eligibility for the accelerated approval pathway, casting a shadow of uncertainty over its timeline to market.

The FDA has set a target action date, known as the PDUFA date, for October 30, 2026. However, in its acceptance letter, the agency noted a "potential review issue," stating its preliminary conclusion that INOVIO has not yet submitted adequate information to justify a fast-track review. The announcement sent INOVIO's stock (NASDAQ: INO) tumbling by over 20%, reflecting investor concern over the potential for a longer, more arduous path to approval for a drug that offers hope to a desperate patient community.

A Life of Repeated Surgeries: The Unmet Need in RRP

For patients with Recurrent Respiratory Papillomatosis (RRP), life is often measured by the time between surgeries. Caused by the human papillomavirus (HPV), specifically types 6 and 11, RRP is characterized by the relentless growth of benign, wart-like tumors in the respiratory tract. These papillomas, while not cancerous, can obstruct the airway, leading to severe breathing difficulties and, in some cases, life-threatening complications.

The current standard of care is surgical removal of the growths. However, the papillomas almost always return, trapping patients in a grueling cycle of repeated procedures. According to INOVIO, patients in its clinical trial had a median of four surgeries in the year before receiving treatment. Each operation carries significant risks, including permanent damage to the vocal cords, which can profoundly impact a person's ability to speak and their overall quality of life. The financial and emotional toll on patients and their families is immense.

There are currently no FDA-approved curative treatments for RRP, creating a critical unmet medical need. Patient advocacy groups, such as The Recurrent Respiratory Papillomatosis Foundation, have long campaigned for the development of non-surgical options that can break the cycle of surgery and improve patient outcomes. It is this desperate need that makes the development of a therapeutic like INO-3107 so significant.

A Promising DNA Medicine Shows Clinical Efficacy

INO-3107 is an investigational DNA medicine, representing a novel technological approach to treating disease. It is designed to function like software for the body's immune system, delivering a DNA plasmid that instructs cells to produce proteins mimicking those from HPV-6 and HPV-11. This process is intended to train the patient's T-cells to recognize and attack HPV-infected cells, thereby preventing or slowing the growth of new papillomas.

The clinical data supporting INOVIO's application has been a source of considerable optimism. In a Phase 1/2 trial of 32 patients, treatment with INO-3107 led to a dramatic reduction in the need for surgery. At the end of the first year, 72% of patients saw a 50% to 100% reduction in surgical interventions. Long-term follow-up data was even more compelling, showing that 86% of evaluable patients maintained this clinical benefit into a second year without any additional dosing. Remarkably, half of those patients required no surgeries at all during that period.

This promising profile earned INO-3107 both Orphan Drug and Breakthrough Therapy designations from the FDA, signals that the agency recognized its potential to provide a substantial improvement over available care for a serious, rare disease. The treatment was also reported to be well-tolerated, with most side effects being low-grade issues like injection site pain.

The Accelerated Approval Pathway Under Scrutiny

The FDA's accelerated approval program was created to speed the availability of drugs for serious conditions that fill an unmet medical need. It allows for approval based on a "surrogate endpoint"—a marker, such as a reduction in tumor size or, in this case, a reduction in the number of surgeries—that is considered reasonably likely to predict a real clinical benefit to patients. However, a condition of this pathway is that the company must conduct post-market confirmatory trials to prove the drug's benefit. If these trials fail, the FDA can withdraw the approval.

In recent years, the FDA has been tightening its standards for this pathway, partly in response to criticism over "dangling approvals" where confirmatory studies were delayed for years. Recent legislation has given the agency more power to enforce these requirements. The agency's hesitation regarding INO-3107 suggests it may not yet be fully convinced that a reduction in surgeries, while clinically meaningful, is a sufficiently validated surrogate endpoint to predict long-term benefit without a more robust data package or a confirmatory trial already underway.

INOVIO's situation is a case study in the tension between the desire to expedite innovative treatments for devastating diseases and the regulatory imperative to ensure drugs are proven safe and effective. The FDA's stance highlights the high bar that novel technologies, like DNA medicines, must clear to gain market access.

Market Reacts as INOVIO Vows to Engage FDA

Despite the regulatory hurdle, INOVIO is standing by its drug and its strategy. The company has stated it is not currently planning to seek approval under the traditional, slower pathway and will instead request a meeting with the FDA to address the agency's concerns and fight to remain eligible for accelerated approval.

"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," said Dr. Jacqueline Shea, INOVIO's President and Chief Executive Officer, in a statement. "Every surgery matters to patients and we look forward to continuing to collaborate with the FDA during the BLA review cycle."

The coming months will be critical for the company. The outcome of its discussions with the FDA will determine whether INO-3107 can achieve a faster path to patients or if it will face a more prolonged and uncertain regulatory journey. For the thousands of people living with RRP, the decision could mean the difference between continued cycles of surgery and the hope of a truly transformative therapy.