INO-3107 Could Become the Second Treatment for Recurrent Respiratory Papillomatosis on October 30th

Kim McClellan was 5 years old in 1971 when doctors found wart-like growths in her throat. She has written that the next 50 years brought about 250 surgeries, growths that spread into her lungs, and a permanent tracheostomy, a breathing tube through the neck (Global Genes, 2022). She now leads the Recurrent Respiratory Papillomatosis Foundation, and for almost all of those years there was no drug to offer anyone with her disease, only the next operation.

That changed on August 14, 2025, when the FDA approved Papzimeos, the first treatment for recurrent respiratory papillomatosis (RRP). A second could follow soon. The FDA's target date to decide on INOVIO's INO-3107, a DNA medicine that trains the immune system against the virus behind the disease, is October 30, 2026.

Recurrent Respiratory Papillomatosis Is HPV in the Airway, and Surgery Only Resets the Clock

RRP is caused by 2 types of human papillomavirus, HPV 6 and HPV 11, the same low-risk types behind genital warts. In the airway they produce benign growths called papillomas, most often on the vocal cords, and the first sign is usually a hoarse or changing voice. Children are thought to pick up the virus from their mother at birth; adults are thought to acquire it through sexual contact (NIDCD). The US sees roughly 2 or fewer cases per 100,000 children and 2 to 3 per 100,000 adults, and about 1,000 new cases a year (FDA, 2025).

The growths are not cancer, but they will not stay gone. Surgeons remove them with a laser or a microdebrider, a small rotating blade, and the virus left in the surrounding tissue grows new ones. Some patients return to the operating room every few weeks (NIDCD). Drugs such as cidofovir have been tried alongside surgery with mixed results, and doctors now use the cancer drug bevacizumab for severe or lung disease; in a national survey of 8 patients treated that way, all 8 responded, 1 of them completely (Best et al., The Laryngoscope, 2017).

The airway itself can close. Morgan Toll was diagnosed at 8 months old and had more than 200 surgeries by age 11, according to Johns Hopkins, which treated her. The disease went quiet for more than a decade, then came back when she was 22, and scarring had narrowed her windpipe to 3 millimeters. She needed an emergency tracheotomy and a series of 7 surgeries to remove the scar tissue before the tube could come out (Johns Hopkins Medicine, 2016).

“Until today, no therapies have been approved for RRP.”

U.S. Food and Drug Administration, August 14, 2025

Precigen's Papzimeos (zopapogene imadenovec) uses a modified adenovirus that cannot copy itself to deliver pieces of HPV 6 and 11 proteins, so the immune system learns to attack the infected cells. Adults get 4 injections under the skin over 12 weeks, on days 1, 15, 43 and 85. The papillomas are removed surgically before the first dose, and any visible growth is removed again before doses 3 and 4 (FDA prescribing information).

In the pivotal trial of adults who had needed at least 3 surgeries a year, 18 of 35 (51.4%) needed no surgery at all in the 12 months after treatment. Most of those responses held: Precigen reported in October 2025 that 15 of the 18 were still surgery-free at a median follow-up of 36 months (Precigen, 2025). The FDA granted full approval with no confirmatory trial required. At the approval, McClellan called it "a momentous milestone for the RRP community" (Precigen, 2025).

INO-3107 Faces an FDA Decision on October 30th

INO-3107 goes after the same 2 viral types by a different route. It is made of plasmids, small circles of DNA carrying instructions for HPV 6 and 11 proteins. Each dose is injected into a muscle, usually the upper arm, and followed by a brief electrical pulse from INOVIO's CELLECTRA device that opens the muscle cells long enough for the DNA to get in. The cells make the viral proteins, and the immune system answers with T cells that hunt down infected airway cells. In the trial, researchers could see new T cell groups travel from the blood into the papillomas themselves (Mau et al., Nature Communications, 2025).

The Phase 1/2 trial (NCT04398433) enrolled 32 adults who had needed at least 2 surgeries in the year before treatment, a median of 4. In the year after, 81% (26 of 32) needed fewer surgeries, 28% (9 of 32) needed none, and the median patient dropped by 3 procedures. Side effects linked to treatment occurred in 41% and were all low grade (Mau et al., 2025). In a follow-up study of 28 of the patients, with no extra doses, half needed no surgery in the second year, and the average fell from 4.1 surgeries before treatment to 1.7 in year 1 and 0.9 in year 2 (INOVIO, 2025).

Read on its own, the chart favors Papzimeos on the strictest measure, and INOVIO argues the comparison is incomplete for 2 reasons it states publicly: its regimen does not require surgery during the dosing window, and a DNA medicine is not weakened by the immune system learning to recognize a viral vector, which could matter if patients need repeat courses (INOVIO, 2025 and 2026). Only a trial that treats similar patients the same way could settle which works better, and none is running.

The Accelerated Approval Question Hanging Over the INO-3107 Review

INOVIO finished its application on November 3, 2025 and asked for accelerated approval, a pathway that lets the FDA approve a drug on early evidence on the condition that a confirmatory trial follows. When the FDA accepted the application on December 29, 2025, it put it on standard review rather than the faster priority review INOVIO had requested, and it flagged a problem. In the company's words, the FDA's preliminary view was that INOVIO had not submitted adequate information to justify eligibility for the accelerated approval pathway (INOVIO SEC filing, 2025).

Context explains the tension. Accelerated approval is reserved for drugs that offer a meaningful advantage over existing treatment for a serious condition, and about 11 weeks before INOVIO finished its application, RRP got its first fully approved drug. INOVIO has since held its mid-cycle and late-cycle meetings with the FDA and says all scheduled inspections are complete. At an informal meeting over the summer, the FDA did not discuss its preliminary comment on eligibility, and said feedback on the design of a confirmatory trial would be forthcoming (INOVIO, 2026). The outcome on October 30 could be an approval under either pathway or a complete response letter asking for more.

8 RRP Clinical Trials Are Open, and 7 Have US Sites

Acromegaly, another rare disease on this site, has 17 open studies but only 3 with US sites for patients. RRP runs the other way. As of September 23, 2026, ClinicalTrials.gov lists 8 RRP studies recruiting or about to open, and 7 have a US site. None of them is testing INO-3107. Its trial is finished, and we could not find a confirmatory study on ClinicalTrials.gov.

Atlanta, Bethesda and Cincinnati: Papzimeos retreatment (NCT06538480)

Precigen's Phase 4 study of giving Papzimeos again and of whether the vector is shed from the body. Recruiting.

Scottsdale, Arizona: dendritic cell vaccine (NCT07317154)

Mayo Clinic's Phase 1 study of a vaccine made from each patient's own immune cells. Recruiting.

New Haven, Connecticut: pembrolizumab and lenvatinib (NCT04645602)

A Yale Phase 2 study combining a cancer immunotherapy with a targeted pill. Recruiting.

Columbus, Ohio: Gardasil-9 booster (NCT07339163)

An Ohio State study of whether an HPV vaccine booster lengthens the time between surgeries in adults. Not yet recruiting.

Bethesda, Maryland: bevacizumab plus PRGN-2012 (NCT07756840)

A Phase 2 study at the NIH Clinical Center pairing bevacizumab with the drug later approved as Papzimeos. Not yet recruiting.

New Haven, Connecticut: pulmonary RRP natural history (NCT06412172)

A Massachusetts General Hospital study of RRP that has spread to the lungs. Recruiting.

Sioux Falls, South Dakota: rare disease registry (NCT01793168)

Sanford Health's CoRDS registry, open to many rare diseases including RRP. Recruiting.

Paris, France: juvenile RRP cohort (NCT06000527)

A French national cohort of children with RRP at Necker hospital. Recruiting.

HPV Vaccination Is Making Childhood RRP Rarer

The strongest tool against juvenile RRP may already exist. The HPV vaccines in routine use protect against types 6 and 11, and fewer young women carrying those types means less virus to pass to babies at birth. A CDC-led study of 576 US children with RRP, born between 2004 and 2013, found the rate of new cases fell by 75% (Meites et al., Clinical Infectious Diseases, 2021).

For families already living with RRP, the vaccine will not clear an existing infection, and the trial at Ohio State is only now asking whether a booster helps adults who have the disease. For the next generation, though, the math has already changed. The Recurrent Respiratory Papillomatosis Foundation is the main US patient organization for families living with RRP, and the RRP disease page collects the treatments and trials in one place.