FDA Grants Accelerated Approval to First Plasmid DNA Immunotherapy for Rare Airway Disease

The U.S. Food and Drug Administration has granted accelerated approval to a novel immunotherapy designed to reduce the relentless cycle of surgeries for adults with a rare airway disease. The decision makes Voceryq the first plasmid DNA-based immunotherapy approved in the United States. The manufacturer, INOVIO Pharmaceuticals, expects to begin shipping the treatment within sixty days.[1][2]

Voceryq targets recurrent respiratory papillomatosis, a chronic condition driven by human papillomavirus types 6 and 11. The virus causes benign, wart-like growths called papillomas to form along the respiratory tract, most commonly on the vocal cords. These tumors can severely impair breathing, swallowing, and speech.[1]

Because the underlying viral infection persists in the airway tissue, surgical removal of the growths does not cure the disease. Tumors frequently return, forcing some patients to undergo excision procedures as often as every few weeks. Each successive surgery carries a cumulative risk of permanent damage to the vocal cords.[1][5]

"Adults living with recurrent respiratory papillomatosis often face an exhausting and relentless cycle of repeated surgeries, managing their disease, but never truly escaping it," said Karim Mikhail, director of the FDA's Center for Biologics Evaluation and Research. He noted the approval offers patients a chance at fewer disruptions and more time living on their own terms.[1][5]

Training the immune system

Rather than physically removing the tumors, Voceryq is designed to train the patient's immune system to recognize and attack the infected cells. The therapy consists of two distinct DNA plasmids delivered via an intramuscular injection. One plasmid provides genetic instructions related to the specific HPV proteins, while the second encodes an immune-stimulating molecule called interleukin-12.

To ensure the plasmids enter the body's cells effectively, the treatment is administered using a proprietary handheld device that performs electroporation. This technique applies brief electrical pulses to the injection site, temporarily opening microscopic pores in the cell membranes. The straightforward refrigeration requirements mean the therapy can be administered in a standard doctor's office.[2][5]

The FDA based its accelerated approval on data from the phase 1/2 RRP-001 clinical trial, which enrolled 32 adults who had undergone multiple surgeries in the previous year. The primary efficacy population consisted of 26 patients who had required at least three surgical excisions in the twelve months before receiving their first dose.[4]

Within that group, patients had endured a median of 4.5 surgeries in the prior year, with some requiring as many as eight. Following the four-dose treatment regimen, seven of those 26 patients—representing 27 percent of the cohort—achieved a complete response. They required no surgical intervention at all during the subsequent twelve months of follow-up.[4]

INOVIO noted that such a prolonged period without surgery is not expected in the natural, untreated course of the disease. The therapy was generally well-tolerated, with all 32 trial participants completing the study. The most common adverse reactions were transient and mild, including injection site pain, fatigue, headache, and temporary muscle contractions from the electroporation device.[1][4]

A shifting regulatory landscape

The path to authorization was not entirely smooth for the manufacturer. In March, the FDA initially indicated that INOVIO had not submitted adequate information to pursue the expedited accelerated approval pathway. Industry analysts viewed the hesitation as part of a broader, tightened regulatory approach toward rare diseases under the agency's current leadership.[5]

The agency ultimately granted the accelerated approval based on the surrogate endpoint of reduced surgical frequency, which is reasonably likely to predict long-term clinical benefit. To maintain the authorization, INOVIO must conduct a confirmatory clinical trial. The FDA requires the company to submit a draft protocol by the end of 2026, with final alignment expected by mid-2027.[2][4][5]

Patient advocacy groups have celebrated the milestone as a fundamental shift in how the medical community approaches the condition. "In reaching this milestone, we have shown that patient voices matter in the drug development process," said Kim McClellan, president of the Recurrent Respiratory Papillomatosis Foundation. She emphasized the critical need for non-surgical options.[5]

"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," said Dr. Simon Best. The Johns Hopkins University otolaryngology associate professor served as a lead investigator for the pivotal trial.

Expanding non-surgical options

Voceryq is not the only recent breakthrough for the patient community. In August 2025, the FDA granted full approval to Papzimeos, a nonreplicating adenoviral vector-based immunotherapy manufactured by Precigen. That treatment also targets the HPV proteins responsible for the disease, and its pivotal trial saw 51 percent of patients avoid surgery for a full year.

While the two therapies cannot be directly compared due to different trial designs and patient populations, they offer mechanistically distinct alternatives for a disease that previously had none. Voceryq relies on plasmid DNA, whereas Papzimeos utilizes a viral vector. The dual approvals give clinicians multiple tools to stimulate an immune response against the persistent viral infection.

The disease itself remains rare, with recent systematic reviews estimating an adult-onset incidence of roughly 0.2 to 3.9 cases per 100,000 people. However, researchers note that national prophylactic HPV vaccination programs have been associated with significantly lower rates of juvenile-onset disease in countries where the data is tracked.

For the estimated 25,000 people currently living with the condition in the United States, the immediate focus is access. INOVIO anticipates full field deployment of its medical and commercial teams during the first quarter of 2027. Patients are encouraged to consult their specialists to determine if the new immunotherapy aligns with their specific clinical history.[2][5]