INOVIO announced the U.S. Food and Drug Administration (FDA) granted orphan drug designation for INO-3107, its DNA medicine being evaluated in a Phase 1/2 trial for treatment of recurrent respiratory papillomatosis (RRP).

RRP is a rare disease caused by human papillomavirus (HPV) types 6 and 11 infections. RRP causes noncancerous tumor growths leading to life-threatening airway obstructions and can progress to cancer in rare cases. Currently, the disease is incurable and is mostly treated by surgery to remove the tumor growths to temporarily restore the airway. The tumor almost always recurs and the surgery must be repeated, often multiple times a year. RRP can severely impact the quality of life for those living with the disease.

Orphan drug designation is intended to advance drug development for rare diseases. FDA grants orphan drug status to medicines intended for the prevention, diagnosis, and treatment of rare diseases or conditions. In the United States, an orphan disease is defined as a disease or condition with a prevalence of less than 200,000 patients in the United States annually. This orphan drug designation from the FDA qualifies INO-3107 for various development incentives, including a tax credit on expenditures incurred in clinical studies, a waiver of the New Drug Application (NDA) fee, research grant awarded by the FDA, and, 7 years of U.S. market exclusivity upon approval for the treatment of RRP.

"Receiving FDA's orphan drug designation for INO-3107 is an important milestone in the development of INOVIO's DNA medicine for this rare disease and clearly underscores the importance of addressing the unmet medical need for this debilitating condition," Ami Shah Brown, Ph.D., MPH, INOVIO's Senior Vice President, Regulatory Affairs, said.

The open-label, multicenter INO-3107 Phase 1/2 trial is currently open to enrollment to recruit 63 subjects in the U.S. and will evaluate the efficacy, safety, tolerability, and immunogenicity of INO-3107 in subjects with HPV 6 and/or 11-associated RRP who have required at least two surgical interventions per year for the past three years for the removal of associated papilloma(s). For this study, adult subjects will first undergo surgical removal of their papilloma(s) and then receive four doses of INO-3107, one every three weeks. The primary efficacy endpoint will be a doubling or more in the time between surgical interventions following the first dose of INO-3107 relative to the frequency prior to study therapy.

Last year, INOVIO published data from its pilot clinical study of INO-3106 (DNA medicine candidate targeting HPV 6-caused RRP) in the scientific journal Vaccines (MDPI). Study results demonstrated that INO-3106 generated immunogenicity and engagement and expansion of an HPV 6-specific cellular response, including cytotoxic T cells. The paper also showed that INOVIO's immunotherapy allowed two out of two patients who previously required approximately two surgeries per year for several years to manage this disease to delay the need for surgery to a robust degree; one patient was able to delay surgery for over a year and a half (584 days surgery-free) and a second remained surgery-free for over two and a half years (over 915 days surgery-free).

Recurrent respiratory papillomatosis (RRP) is a rare disease (estimated at 15,000 active cases in the U.S.) that is characterized by the growth of tumors in the respiratory tract caused by the human papillomavirus. Although benign, papillomas can cause severe, even life-threatening airway obstruction and respiratory complications. A distinguishing aspect of this disease is the tendency for the papilloma to recur after surgical procedures to remove them. Left untreated, if RRP develops in the lungs, affected individuals can potentially experience recurrent pneumonia, chronic lung disease (bronchiectasis) and, ultimately, progressive pulmonary failure. In rare cases papillomas can become cancerous (malignant transformation) developing into squamous cell carcinoma. Additional symptoms of RRP can include hoarse voice, difficulty in sleeping and swallowing, and chronic coughing. RRP symptoms are usually more severe in children than in adults. In children, the disorder is most often diagnosed at or around the age of four years. In adults, the disorder occurs most often in the third or fourth decade.