FDA Approves First Plasmid DNA-Based Immunotherapy for Adults With RRP

The FDA granted accelerated approval on October 30 to a combination of doruxapapogene ralaplasmid and lalikinogene sifuplasmid-gxfd (Voceryq; Inovio) for the treatment of adults with recurrent respiratory papillomatosis (RRP), marking the first approval of a plasmid DNA-based immunotherapy in the US.¹

RRP is a rare, chronic disease caused by human papillomavirus (HPV) that leads to the formation of small, wart-like growths, called papillomas, in the respiratory tract, most often around the larynx, particularly the vocal cords. These growths can cause hoarseness, chronic cough, and voice changes. In severe cases, they can also spread to other parts of the respiratory tract and cause difficulty breathing. Although surgery can remove the growths, RRP has no cure. Because the virus can persist in the tissue even after the growths are removed, patients often require repeated procedures.

The October 30 approval offers patients with RRP a new therapeutic option designed to target HPV-infected cells. The treatment is intended to reduce the frequency of surgical interventions, an important consideration for patients who often require repeated procedures and have limited treatment options.

The treatment is a recombinant plasmid DNA-based immunotherapy administered via intramuscular injection. It is designed to stimulate an immune response against cells infected with HPV types 6 and 11, which cause RRP.

“Today’s approval represents a meaningful scientific breakthrough: a plasmid DNA-based immunotherapy that harnesses the body’s own immune system to fight the underlying cause of RRP,” Karim Mikhail, BPharm, MSc, Director of the Center for Biologics Evaluation and Research, said in a news release. “For patients, that could mean fewer surgeries, fewer disruptions, and more time living their lives on their own terms. The FDA is proud to help bring that possibility within reach.”

Study Findings Support Reduced Surgical Burden in RRP

The approval was supported by data from the RRP-001 study (NCT04398433), which evaluated the treatment in 32 adults with RRP who had undergone 2 or more surgeries in the year before treatment.² During the dosing window, no additional papilloma surgical excisions were required per protocol.

Of the 32 patients, 26 required 3 or more papilloma excisions in the 12 months before treatment and were included in the efficacy evaluation. The median number of surgical excisions in the 12 months before the first dose in this efficacy population was 4.5 (range, 3-8). After 12 months of follow-up, 7 of the 26 patients (27%; 95% CI: 12%-48%) demonstrated a complete response, defined as requiring no surgical excision of papillomas.

The most commonly reported adverse events were injection site reactions, headache, fatigue, hypertension, nausea, and dizziness.¹ Most treatment-related adverse reactions were grade 1 or 2 and transient, with no grade 4 or 5 common adverse events.²

“The approval of VOCERYQ is an important step in improving the quality of life for RRP patients, as every surgery carries the risk of laryngeal injury,” Simon Best, associate professor of otolaryngology at Johns Hopkins University and an RRP-001 lead investigator, said in a news release. “I believe it is in the best interest of RRP patients that the standard of care quickly transition away from surgical interventions to immunotherapy after RRP is diagnosed.”

As the combination regimen received accelerated approval, which allows the FDA to approve drugs or biologics for serious or life-threatening conditions based on an effect on a surrogate or intermediate clinical end point reasonably likely to predict clinical benefit, Inovio must conduct postapproval clinical trials to verify and describe the treatment’s clinical benefit.¹ The FDA requires Inovio to submit a draft protocol for the confirmatory study by the end of 2026, with the expectation of aligning on a final protocol by mid-2027.²

References

1. FDA approves first plasmid DNA-based immunotherapy for adults with recurrent respiratory papillomatosis. News release. FDA. October 30, 2026. Accessed October 31, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-plasmid-dna-based-immunotherapy-adults-recurrent-respiratory-papillomatosis
2. INOVIO announces FDA accelerated approval of VOCERYQ, an immunotherapy to reduce the frequency of surgery in adults with recurrent respiratory papillomatosis (RRP). News release. Inovio. October 30, 2026. Accessed November 2, 2026. https://ir.inovio.com/news/news-details/2026/INOVIO-Announces-FDA-Accelerated-Approval-of-VOCERYQ-an-Immunotherapy-to-Reduce-the-Frequency-of-Surgery-in-Adults-with-Recurrent-Respiratory-Papillomatosis-RRP/default.aspx