FDA Grants Breakthrough Therapy Designation to Precigen for RRP Gene Therapy

Rare Daily Staff

The U.S. Food and Drug Administration granted Precigen Breakthrough Therapy Designation for its experimental immunotherapy for the treatment of recurrent respiratory papillomatosis, a rare condition that causes benign tumors in the respiratory tract.

Recurrent respiratory papillomatosis (RRP) is a difficult-to-treat and sometimes fatal neoplastic disease that is caused by infection with HPV 6 or HPV 11. Currently, there is no cure for RRP and the current standard-of-care is repeated endoscopic debulking with ablation or excision of papillomatous lesions. Recurrence of papilloma after surgical removal is common and repeated procedures are required to debulk and monitor the disease, which exposes patients to anesthetic and surgical risks, as well as emotional distress. RRP morbidity and mortality results from the effects of papilloma mass on the vocal cords, trachea, and lungs, which may cause voice changes, stridor, airway occlusion, loss of lung volume, and/or post-obstructive pneumonia. Although rare, one to three percent of RRP cases can transform into invasive squamous cell carcinoma.

Precigen’s experimental therapy PRGN-2012 incorporates optimized antigen design that uses gorilla adenovector technology, part of Precigen’s proprietary AdenoVerse platform, to elicit immune responses directed against cells infected with human papillomavirus type 6 (HPV 6) or HPV type 11 (HPV 11). Gorilla adenovectors have numerous advantages, including the ability for repeat administration, the inability to replicate in vivo, and the ability to deliver a large genetic payload. PRGN-2012 has previously been granted Orphan Drug designation in patients with RRP by the FDA.

FDA’s Breakthrough Therapy designation expedites the development and review of medicines which are intended to treat serious or life-threatening diseases, and in which preliminary clinical evidence demonstrates substantial improvement on clinically significant endpoints over available therapies.

“Standard-of-care for RRP consists of repeated surgical interventions, and there are currently no approved therapeutics. The potential of PRGN-2012 to reduce surgical interventions and improve outcomes for these patients makes us incredibly proud to receive the FDA’s Breakthrough Therapy Designation,” said Helen Sabzevari, president and CEO of Precigen. “This designation will enable our direct engagement with senior leadership at the FDA regarding the most efficient product development pathway, including eligibility for rolling and priority review of a BLA to support a potential PRGN-2012 registration.”

The Breakthrough Therapy Designation was based on the clinical evidence for PRGN-2012 generated in the phase 1 study, which showed strong response at the recommended phase 2 dose in patients who had an average of 5.8 RRP surgeries (range 3 – 10) in the year prior to PRGN-2012 treatment. PRGN-2012 treatment resulted in 50 percent of patients (6 out of 12) in complete response, requiring no post-treatment surgeries with a minimum follow up of 12 months.

PRGN-2012 treatment resulted in a reduction of surgeries in 83 percent (10 out of 12) patients in the 12 months following treatment. PRGN-2012 induced robust de novo HPV-specific T-cell immune response in RRP patients. PRGN-2012 was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2. The phase 1 clinical evidence demonstrating safety and efficacy of PRGN-2012 for the treatment of RRP patients, who have no approved therapeutic option, provides the foundation for this Breakthrough Therapy Designation.

PRGN-2012 is currently being evaluated in a phase 2 study in adult patients with RRP. The company said patient follow up is ongoing as are discussions with the FDA regarding potential rapid development paths to enable a future submission of a Biologics License Application.

Photo: Helen Sabzevari, president and CEO of Precigen