FDA Approves First Plasmid DNA-based Immunotherapy for Adults with Recurrent Respiratory Papillomatosis
The U.S. Food and Drug Administration has granted accelerated approval for Voceryq (doruxapapogene ralaplasmid and lalikinogene sifuplasmid-gxfd) for treatment of adults with recurrent respiratory papillomatosis (RRP), a rare disease caused by human papillomavirus (HPV) that leads to the formation of small, wart-like growths in the patient’s airways. This approval, the first for a plasmid DNA-based immunotherapy in the U.S., offers patients a new therapeutic option that targets the root cause of RRP and has been shown to reduce the burden of surgical intervention, representing an important step forward for a patient population with limited treatment options.
“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., M.S., Director of the Center for Biologics Evaluation and Research (CBER). “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.”
The agency based this accelerated approval on clinical trial data showing Voceryq helps reduce the frequency of surgical procedures required to remove growths in adult patients with RRP — an intermediate clinical endpoint reasonably likely to predict clinical benefit. The accelerated approval pathway allows the FDA to approve drugs or biologics for serious or life-threatening conditions based on an effect on a surrogate or intermediate clinical endpoint reasonably likely to predict clinical benefit. The manufacturer must conduct post-approval clinical trials to verify and describe Voceryq’s clinical benefit.
RRP is a rare, chronic disease in which wart-like growths caused by HPV types 6 and/or 11 form in the airways, most often around the larynx (voice box), particularly the vocal cords. These growths, called papillomas, can cause symptoms like hoarseness, chronic cough, and voice changes, and in severe cases can spread to other parts of the respiratory tract, causing difficulty breathing. While surgery can remove the growths, there is no cure, and the virus persists in the tissue even after the growths are removed, so patients often need repeated procedures over many years. In some cases, RRP carries a risk of becoming cancerous over time.
Voceryq is a recombinant plasmid DNA-based immunotherapy that delivers two plasmids (small pieces of DNA originally derived from bacteria) into the body’s cells, one of which contains the genetic instructions for specific HPV proteins and the other an immune response-enhancing molecule called IL-12. The therapy is designed to stimulate the immune system to respond to and attack cells infected by the specific types of HPV that cause RRP (types 6 and 11). Voceryq is administered via intramuscular (IM) injection using the CELLECTRA 5PSP Device, which delivers the dose and facilitates electroporation, a technique which uses brief electrical pulses to temporarily and reversibly create pores in the cell membranes to enable the delivery of Voceryq into the body’s cells.
The safety and effectiveness of Voceryq was evaluated in an open-label multicenter clinical trial in 32 adults diagnosed with RRP. Eligible patients had two or more surgeries to remove laryngotracheal papillomas in the 12 months prior to Voceryq treatment, including a scheduled surgery at trial entry. Seven (27%) out of 26 patients who had at least three baseline surgeries did not require any surgery intervention during the first year after treatment.
The most commonly reported adverse reactions to Voceryq were injection site reactions, headache, fatigue, hypertension (high blood pressure), nausea, and dizziness. Adverse effects associated with the electroporation technique may include brief muscle contractions or tetany, temporary bleeding at the administration site, anxiety, vasovagal reactions including lightheadedness and dizziness, transient changes in creatine phosphokinase, erythema (skin redness) at the injection site, and pain at the injection site.
The FDA granted Voceryq Breakthrough and Orphan Drug designations. The FDA granted accelerated approval of Voceryq to Inovio Pharmaceuticals, Inc.
