INOVIO Wins FDA Approval for VOCERYQ to Reduce RRP Surgeries

The U.S. Food and Drug Administration (FDA) granted accelerated approval on October 30, 2026, to VOCERYQ™ (doruxapapogene ralaplasmid and lalikinogene sifuplasmid-gxfd; INO-3107), INOVIO’s plasmid DNA-based immunotherapy, to reduce the frequency of surgical papilloma excisions in adults with recurrent respiratory papillomatosis (RRP).

The approval makes VOCERYQ the first plasmid DNA-based immunotherapy approved in the United States. Continued approval may depend on confirmation of clinical benefit in a post-approval study.

Phase 1/2 Results Support Accelerated Approval

The FDA based its decision on findings from the open-label Phase 1/2 RRP-001 study (NCT04398433), which evaluated VOCERYQ in 32 adults who had undergone at least two surgeries during the preceding 12 months.

The efficacy analysis included 26 patients with at least three surgical excisions during the previous year. These patients had a median of 4.5 surgeries at baseline, indicating a substantial surgical burden.

Following treatment, seven of the 26 patients (27%; 95% CI, 12% to 48%) required no surgical papilloma excision during the subsequent 12 months. This outcome, defined as a complete response, formed the principal clinical evidence supporting accelerated approval.

The FDA considered freedom from surgical intervention an intermediate endpoint reasonably likely to predict clinical benefit. However, the study was open-label and lacked a control group, limiting direct comparisons with standard surgical management. The confirmatory study will therefore be important in establishing the durability and extent of the observed benefit.

Administration and Safety Profile

VOCERYQ is administered intramuscularly using INOVIO’s CELLECTRA® 5PSP electroporation device, which delivers brief electrical pulses to facilitate plasmid DNA uptake by cells.

The treatment consists of four doses administered every three weeks over nine weeks. Surgical debulking of visible papillomas is required before the first dose.

The most common adverse reactions, reported in more than 5% of patients, included injection-site reactions, headache, fatigue, hypertension, nausea and dizziness. Most were Grade 1 or 2.

Electroporation-related effects may include temporary muscle contractions, bleeding at the administration site and vasovagal reactions. The prescribing information recommends monitoring patients for at least 30 minutes following administration. Administration should be avoided in extremities with ipsilateral pacemakers or implantable defibrillators, metal implants or skin abnormalities at the treatment site.

Mechanism and Disease Background

VOCERYQ combines two plasmids: one encoding HPV-6 and HPV-11 antigens and another encoding interleukin-12 (IL-12), which helps stimulate immune responses against HPV-infected cells.

RRP is a rare, chronic disease primarily associated with HPV types 6 and 11. It causes recurrent papillomas in the respiratory tract, particularly around the larynx and vocal cords, leading to hoarseness, coughing and, in severe cases, breathing difficulties.

Surgery remains the standard treatment, but it does not eliminate the underlying viral infection. Consequently, papillomas can recur, requiring repeated procedures. VOCERYQ introduces an immunotherapy approach aimed at reducing this surgical burden. The product previously received FDA Breakthrough Therapy and Orphan Drug designations.

Confirmatory Study and Commercial Outlook

INOVIO must submit a draft confirmatory study protocol to the FDA by the end of 2026, with a final protocol expected by mid-2027. The study will be central to determining whether the reduction in surgical interventions observed in RRP-001 translates into sustained clinical benefit.

On the commercial front, INOVIO expects VOCERYQ to become available to order and ship approximately 60 days after approval, with full field deployment anticipated in the first quarter of 2027.

The approval introduces a plasmid DNA-based immunotherapy option for adults with RRP, a disease historically managed through repeated surgical procedures. However, the confirmatory evidence will determine whether VOCERYQ can deliver a sustained reduction in surgical burden.

References

INOVIO Announces FDA Accelerated Approval of VOCERYQ™, an Immunotherapy to Reduce the Frequency of Surgery in Adults with Recurrent Respiratory Papillomatosis (RRP), INOVIO, 30 October 2026

FDA Approves First Plasmid DNA-based Immunotherapy for Adults with Recurrent Respiratory Papillomatosis, US FDA, 30 October 2026

INO-3107 With Electroporation (EP) in Participants With HPV-6- and/​or HPV-11-Associated Recurrent Respiratory Papillomatosis (RRP), ClinicalTrials.gov ID NCT04398433