FDA grants accelerated approval to DNA immunotherapy for adult recurrent respiratory papillomatosis

The FDA has granted accelerated approval to doruxapapogene ralaplasmid and lalikinogene sifuplasmid-gxfd (Voceryq; INOVIO) to reduce the frequency of surgical papilloma excisions in adults with recurrent respiratory papillomatosis (RRP), the company announced on October 30, 2026. Continued approval for this indication may depend on verification of clinical benefit in confirmatory studies.¹

“This new FDA-approved therapy brings us an important step closer to ensuring every RRP patient has access to a non-surgical treatment option that works for them. In reaching this milestone, we have shown that patient voices matter in the drug development process,” said Kim McClellan, president of the RRP Foundation.

RRP produces wart-like papillomas in the respiratory tract, most often on and around the vocal cords, and can become life-threatening when tumors obstruct the airway. The disease is caused by human papillomavirus (HPV), most commonly HPV 6 and HPV 11, and has no cure. Surgical removal is the most common treatment, but tumors frequently return, and some patients need procedures as often as every few weeks.²

What did the RRP-001 trial show?

Approval rested on complete response, defined as no need for surgical intervention for 12 months after treatment. The pivotal RRP-001 study enrolled 32 adults with RRP who had undergone 2 or more surgeries in the year before treatment; all 32 completed the study, and none required additional papilloma excisions during the dosing window.¹

The efficacy population included 26 patients with 3 or more surgeries in the prior 12 months and a median of 4.5 excisions (range, 3 to 8) before the first dose. Of those, 7 of 26 (27%; 95% CI, 12%-48%) achieved a complete response after 12 months of follow-up. INOVIO stated that complete response is not expected in the untreated natural history of the disease. Full data have been published in Nature Communications and The Laryngoscope.

“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,” said Simon Best, associate professor of otolaryngology at Johns Hopkins University and a lead investigator for the RRP-001 study.

“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,” added Best.

Dosing, administration, and safety

Treatment consists of a 9-week regimen delivered with the CELLECTRA 5PSP device, following standard-of-care surgical debulking of visible papillomas before the first dose. The most common adverse reactions, occurring in more than 5% of patients, were injection site reactions, headache, fatigue, hypertension, nausea, and dizziness. Most treatment-related reactions were grade 1 or 2 and transient, and no grade 4 or 5 common adverse events occurred.

Patients should be monitored for injection site reactions for at least 30 minutes after treatment. Electroporation-related effects may include muscle contractions, transient bleeding, and vasovagal reactions, and the therapy should be avoided in patients with ipsilateral implantable cardioverter-defibrillators or pacemakers, metal implants, or skin abnormalities at the treatment site.

The FDA has required a draft confirmatory trial protocol by the end of 2026, with final protocol alignment expected by mid-2027. INOVIO expects ordering and shipping to begin in approximately 60 days and full field deployment in the first quarter of 2027. The company estimates at least 25,000 prevalent patients in the United States with RRP, based on ongoing claims data analysis.¹

Perinatal HPV transmission and RRP prevention

RRP occurs in a juvenile-onset form, usually diagnosed before age 5 years and typically more aggressive, and a less common adult-onset form that usually develops after age 14 years. Experts estimate that RRP affects a little over 4 of 100,000 children and about 2 of 100,000 adults, according to the Cleveland Clinic.²

Children can acquire HPV from their mother during vaginal delivery when active genital warts are present, and occasionally during cesarean delivery, suggesting the virus can reach the fetus before birth. Adults with RRP may have acquired HPV at birth, with the virus reactivating later. Avoiding HPV is the primary means of prevention, and the HPV vaccine is effective in preventing RRP. Pregnant patients with genital warts should discuss them with their clinician, although the risk of transmission to the baby is low.

References:

1. 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
2. Recurrent respiratory papillomatosis. Cleveland Clinic. Updated June 2, 2022. Accessed November 2, 2026. https://my.clevelandclinic.org/health/diseases/23101-recurrent-respiratory-papillomatosis