The US Food and Drug Administration (FDA) has granted accelerated approval to INOVIO's doruxapapogeneralaplasmid and lalikinogenesifuplasmid-gxfd (Voceryq) to reduce the frequency of surgical papilloma excisions in adults with recurrent respiratory papillomatosis (RRP), according to an agency news release. The decision provides a nonsurgical treatment option for a rare, HPV-associated airway disease.
The approval marks the first US approval of a plasmid DNA-based immunotherapy. RRP, primarily caused by human papillomavirus (HPV) types 6 and 11, produces recurrent growths in the respiratory tract that can impair speech and breathing. Surgical removal remains the standard treatment, but papillomas frequently recur, requiring repeated procedures.
The immunotherapy contains DNA plasmids encoding HPV-6 and HPV-11 antigens and interleukin-12, designed to stimulate HPV-specific T-cell responses. It is administered by intramuscular injection using the CELLECTRA 5PSP device, delivering electrical pulses to facilitate DNA uptake into cells.
"Adults living with recurrent respiratory papillomatosis often face an exhausting and relentless cycle of repeated surgeries," Karim Mikhail, director of the Center for Biologics Evaluation and Research at the FDA, stated in the agency news release.
The approval was supported by a multicenter, open-label, single-arm phase 1/2 study involving 32 adults who required at least 2 surgical interventions during the preceding 12 months. Safety and tolerability were the study's primary end point, with changes in surgical frequency assessed as a secondary end point.
Among 26 patients who required at least 3 surgeries before treatment, 7 required no surgical papilloma excisions during the subsequent 12 months. The median number of surgeries in this efficacy population before treatment was 4.5. The study lacked a concurrent control group, limiting conclusions about comparative efficacy.
According to INOVIO's October 30 press release, most treatment-related adverse reactions were mild or moderate. Common adverse reactions included injection-site reactions, headache, fatigue, hypertension, nausea, and dizziness.
The FDA prescribing information recommends 4 doses of 6.25 mg administered 3 weeks apart, following surgical removal of visible papillomas before treatment begins. A trained health care professional must administer it using the CELLECTRA device.
The label advises monitoring injection sites for at least 30 minutes after administration and avoiding treatment sites with ipsilateral pacemakers, implantable cardioverter-defibrillators, metal implants, or skin abnormalities because of electroporation-related risks.
Continued approval may depend on verification of clinical benefit in a confirmatory study, noted INOVIO. The company reported that the FDA requires a draft study protocol by the end of 2026, with a final protocol expected by mid-2027.
Sources: FDA Press release,FDA Prescribing information, INOVIO
