The accelerated decision provides an alternative to repeated surgeries for patients with persistent airway growths.
RT’s Three Key Takeaways:
- First-of-Its-Kind Approval: The FDA granted accelerated approval to Voceryq, making it the first plasmid DNA-based immunotherapy approved in the US for adult patients with recurrent respiratory papillomatosis (RRP).
- Reduced Surgical Interventions: Clinical trial results showed that 27% of adult patients who had at least three baseline surgeries required no surgical procedures in the first year after receiving the therapy.
- Electroporation Delivery Mechanism: The treatment uses an intramuscular injection coupled with an electroporation device to introduce plasmids that stimulate immune responses against human papillomavirus types 6 and 11.
The FDA has granted accelerated approval for Voceryq (doruxapapogene ralaplasmid and lalikinogene sifuplasmid-gxfd) to treat adults with recurrent respiratory papillomatosis (RRP), according to the agency.
The regulatory action marks the first approval of a plasmid DNA-based immunotherapy in the US, the FDA says. The biologic is designed to offer healthcare providers and patients an option that targets the disease at its underlying cause rather than managing symptoms solely through repeated surgical procedures.
“Adults living with recurrent respiratory papillomatosis often face an exhausting and relentless cycle of repeated surgeries, managing their disease, but never truly escaping it. 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,” said Karim Mikhail, B Pharm, MS, director of the Center for Biologics Evaluation and Research (CBER), 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.”
Addressing Airway Obstruction in RRP
According to the FDA, RRP is a rare, chronic condition caused by human papillomavirus (HPV) types 6 and 11, leading to the development of wart-like lesions called papillomas throughout the respiratory tract. These benign growths frequently cluster around the larynx and vocal cords, triggering symptoms that include hoarseness, chronic cough, voice changes, and in advanced stages, upper airway obstruction and severe breathing difficulties.
While surgical excision has served as the conventional standard of care to debulk tissue and secure airway patency, the virus persists in mucosal tissue after resection, often requiring patients to undergo recurring surgical interventions across decades, the agency noted. The FDA also stated that RRP carries a long-term risk of malignant transformation in select cases.
Mechanism of Action and Clinical Findings
Voceryq is a recombinant immunotherapy delivering two plasmid DNA molecules into host cells, according to FDA documentation. One plasmid carries genetic instructions for targeted HPV proteins, while the second encodes interleukin-12 (IL-12), an immune-enhancing cytokine. The combination is intended to prime and recruit cellular immune defenses to attack cells harboring HPV types 6 and 11.
The biologic is administered via intramuscular (IM) injection in tandem with the CELLECTRA 5PSP Device, which utilizes electroporation, according to the agency. The proprietary delivery unit delivers controlled, brief electrical pulses to produce transient, reversible openings in cell membranes, facilitating plasmid uptake.
The regulatory clearance was supported by data from an open-label, multicenter clinical study involving 32 adult patients diagnosed with RRP, according to the FDA. Participants were required to have undergone two or more surgical resections for laryngotracheal papillomas within the 12 months preceding enrollment, including an intervention scheduled at trial entry. Among a subset of 26 patients with at least three baseline surgical procedures, seven patients (27%) required zero surgical interventions during the first year after receiving the therapy.
Safety Profile and Regulatory Terms
The most frequently documented adverse events associated with Voceryq included injection site reactions, headache, fatigue, hypertension, nausea, and dizziness, the FDA reported. Reported adverse events linked directly to the electroporation procedure included transient muscle contractions or tetany, localized bleeding at the injection site, anxiety, vasovagal events such as dizziness and lightheadedness, temporary elevations in creatine phosphokinase, erythema, and injection site pain.
The FDA granted Voceryq both Breakthrough Therapy and Orphan Drug designations before awarding accelerated approval to Inovio Pharmaceuticals, Inc. Under the statutory provisions of the accelerated approval pathway, which evaluates intermediate clinical endpoints reasonably likely to predict patient benefit, the manufacturer is required to conduct confirmatory post-approval clinical trials to verify and characterize the clinical benefit of the immunotherapy.
