The U.S. Food and Drug Administration (FDA) has granted priority review to Precigen's Biologics License Application (BLA) for PRGN-2012 (zopapogene imadenovec) for the treatment of adults with recurrent respiratory papillomatosis (RRP), setting a Prescription Drug User Fee Act (PDUFA) target action date of August 27, 2025. This milestone brings the company closer to potentially delivering the first FDA-approved therapeutic for this rare and devastating disease.
A Breakthrough for a Devastating Disease
RRP is a rare, difficult-to-treat, lifelong neoplastic disease of the upper and lower respiratory tracts caused by infection with human papillomavirus (HPV) types 6 or 11. The condition can be fatal and currently has no cure. The standard of care involves repeated surgeries that do not address the underlying cause of the disease and are associated with significant morbidity. Patients often require hundreds of lifetime surgeries, with each procedure increasing the cumulative risk of permanent laryngeal injury.
"The priority review designation is a testament to the FDA's recognition of the significant unmet need for the RRP patient population," said Helen Sabzevari, PhD, President and CEO of Precigen. "RRP patients have never had an FDA-approved therapy, relying instead on repeated surgeries to alleviate the symptoms of RRP without addressing the underlying disease."
Impressive Clinical Results
The BLA is supported by data from the pivotal Phase 1/2 clinical study (NCT04724980), which evaluated the safety and efficacy of PRGN-2012 in adult RRP patients. The study enrolled 38 patients total, with 35 receiving the recommended Phase 2 dose of 5×10¹¹ particle units administered subcutaneously over a 12-week treatment period.
Key findings from the trial, which were presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting and published in The Lancet Respiratory Medicine, include:
- 51% of patients (18 out of 35) achieved Complete Response, requiring no surgeries after treatment
- 86% of patients (30 out of 35) experienced a decrease in surgical interventions in the year after treatment compared to the year prior
- Median number of surgeries reduced from 4 (range: 3-10) pre-treatment to 0 (range: 0-7) post-treatment
- Complete responses have been durable, with some patients remaining surgery-free beyond three years
- PRGN-2012 was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2
- Treatment induced HPV 6/11-specific T cell responses, with significantly greater expansion of peripheral HPV-specific T cells in responders compared to non-responders
- Significant improvement (p < 0.0001) in anatomical Derkay scores and Vocal Handicap Index-10 (VHI-10) scores in complete responders
Innovative Technology Platform
PRGN-2012 is an investigational off-the-shelf AdenoVerse gene therapy designed to elicit immune responses directed against cells infected with HPV 6 or HPV 11. The therapy has received Breakthrough Therapy Designation and Orphan Drug Designation from the FDA, as well as Orphan Drug Designation from the European Commission.
Precigen's AdenoVerse platform utilizes a library of proprietary adenovectors for efficient gene delivery of therapeutic effectors, immunomodulators, and vaccine antigens designed to modulate the immune system. The company's gorilla adenovectors have potentially superior performance characteristics compared to current competition, generating high-level and durable antigen-specific T-cell immune responses with the ability to boost these responses via repeat administration.
Commercial Readiness
Precigen is rapidly advancing its commercial and manufacturing readiness campaign in anticipation of a potential launch in 2025. Based on updated internal analysis derived from review of claims data, the market opportunity for PRGN-2012 in RRP is estimated to be approximately 27,000 adult patients in the US and more than 125,000 patients outside the US.
"We have patients treated with PRGN-2012 who have been surgery-free for more than three years now, bringing hope for an alternative to the cycle of repeated surgeries, which carry immense risk for irreversible damage and significant morbidity," Sabzevari noted. "We look forward to working with the FDA over the coming months during their BLA review and hope to introduce the first FDA-approved therapeutic option to the RRP patient population later this year."
The FDA has indicated that they are not currently planning to hold an advisory committee meeting to discuss this application. If approved, PRGN-2012 would represent a paradigm shift in the treatment of RRP, offering patients an alternative to the cycle of repeated surgeries by addressing the underlying viral cause of the disease.
Financial Position
In December 2024, Precigen raised $87.5 million, including $79.0 million from a private placement offering of convertible preferred stock and an additional $8.5 million from the sale of certain intellectual property and royalty rights related to a non-core asset. The company ended 2024 with $97.9 million in cash, cash equivalents, and investments, extending its cash runway into 2026, beyond the potential commercial launch of PRGN-2012.
"As a result of the preferred stock offering and sale of intellectual property and related royalty rights for a non-core asset, we extended our cash runway into 2026, beyond the potential commercial launch of PRGN-2012 this year. We are preparing for the transition to a commercial stage company and the potential to add product-related revenue," said Harry Thomasian Jr., CFO of Precigen.
The company continues to advance patient enrollment in the confirmatory clinical trial of PRGN-2012 in accordance with FDA guidance to initiate the study prior to submission of the BLA. This milestone brings Precigen one step closer to potentially transforming the treatment landscape for RRP patients who have long awaited a therapeutic alternative to repeated surgeries.
