FDA Grants Priority Review to Precigen's BLA for PRGN-2012 for the Treatment of Adults with Recurrent Respiratory Papillomatosis with PDUFA Target Action Date Set for August 27, 2025

Rhea-AI Summary

Precigen, Inc. (PGEN) announced that the FDA has granted priority review to its biologics license application (BLA) for PRGN-2012 (zopapogene imadenovec), an investigational AdenoVerse gene therapy for treating adults with recurrent respiratory papillomatosis (RRP).

The FDA set a PDUFA target action date of August 27, 2025, with no advisory committee meeting currently planned. If approved, PRGN-2012 would become the first and only FDA-approved therapy for RRP, a rare and devastating chronic disease caused by HPV 6 or HPV 11 infection.

The BLA is supported by pivotal Phase 1/2 clinical study data showing impressive results:

• Over 50% of patients achieved Complete Response
• More than 85% experienced decreased surgical interventions
• Some patients have remained surgery-free for over three years
• The treatment was well-tolerated with no serious adverse events

RRP currently has no cure, with patients relying on repeated surgeries that don't address the underlying cause and can lead to cumulative laryngeal injury. The US adult RRP patient population is estimated at more than 27,000.

Positive

• FDA granted priority review for PRGN-2012 with PDUFA date of August 27, 2025
• If approved, PRGN-2012 would be the first and only FDA-approved therapy for RRP
• Over 50% of patients achieved Complete Response in clinical trials
• More than 85% of patients experienced decreased surgical interventions
• Some patients have remained surgery-free for over three years
• Treatment addresses 27,000+ adult RRP patients in US with no current therapeutic options
• PRGN-2012 received Breakthrough Therapy Designation, Orphan Drug Designation, and accelerated approval pathway

Negative

• FDA approval is still pending with potential regulatory hurdles
• No information provided on pricing or reimbursement strategy
• Potential commercial challenges as first-in-class therapy for rare disease
• Not all patients achieved complete response in clinical trials

Insights

Biotechnology Analyst

The FDA's priority review designation for Precigen's PRGN-2012 gene therapy represents a potentially transformative catalyst for this small-cap biotech company. This regulatory milestone significantly accelerates the path to potential commercialization with a PDUFA date of August 27, 2025, while also validating the therapy's potential to address a critical unmet medical need.

The clinical data supporting this BLA is particularly compelling: over 50% of patients achieved Complete Response (defined as no surgeries required in the 12 months following treatment) and more than 85% experienced reduced surgical interventions. Most remarkably, some patients have remained surgery-free for over three years – a dramatic improvement for a condition that typically requires numerous lifetime surgeries.

From a market perspective, this opportunity is substantial despite RRP's rare disease status. With approximately 27,000 adult patients in the US alone and no FDA-approved therapies, PRGN-2012 would enter an untapped market with high unmet need. Given typical rare disease pricing dynamics and the significant burden of repeated surgeries (both clinically and economically), this therapy could command premium pricing while still demonstrating cost-effectiveness versus the lifetime burden of surgical interventions.

For Precigen, with its modest $536 million market cap, this represents a potential company-transforming opportunity. As the first potential commercial validation of their proprietary AdenoVerse platform, PRGN-2012 approval would not only bring immediate revenue potential but also validate the underlying technology platform that could be leveraged across multiple indications.

The AdenoVerse platform's gorilla adenovectors appear to offer distinct advantages over competing technologies, particularly in generating durable antigen-specific T-cell responses that can be boosted through repeat administration – a critical factor for chronic conditions like RRP. The platform's high-yield manufacturing capabilities further enhance its commercial viability.

Investors should note that the FDA's decision not to hold an advisory committee meeting is typically a positive signal, suggesting the agency doesn't see controversial issues requiring external input. However, execution risks remain around potential manufacturing challenges inherent to complex biologics and the company's commercial infrastructure for a potential launch.

Rare Disease Market Specialist

The FDA's priority review for PRGN-2012 represents a potential watershed moment in RRP treatment, addressing a devastating condition with no approved therapies. This rare disease affects approximately 27,000 adult patients in the US alone, who currently endure an endless cycle of surgeries – some requiring hundreds of lifetime procedures – with each intervention increasing the risk of permanent laryngeal damage.

The economic burden of RRP is substantial, with each surgical procedure estimated to cost $5,000-$12,000, not including lost productivity and quality of life impacts. A therapy that could eliminate or significantly reduce these surgeries would create tremendous value for the healthcare system while addressing a critical unmet need.

The clinical profile of PRGN-2012 is particularly impressive for a rare disease therapy. The 50%+ complete response rate (defined as no surgeries needed for 12 months) represents a dramatic improvement over current standards. Perhaps more remarkable is the durability of response, with some patients remaining surgery-free for 3+ years – suggesting potential for long-term disease modification rather than just symptom management.

For Precigen, securing approval would be transformative. As a company with a modest $536 million market cap, commercializing a therapy for 27,000 patients could dramatically alter their financial trajectory. Even with conservative pricing assumptions typical for rare disease therapies, PRGN-2012 could generate annual revenues exceeding $200 million at peak penetration.

The Orphan Drug designation provides 7 years of market exclusivity upon approval, creating a protected commercial runway. Additionally, the FDA's decision not to convene an advisory committee suggests confidence in the data package, though manufacturing and commercialization execution will remain critical challenges.

Beyond the immediate commercial opportunity, this potential approval would validate Precigen's proprietary AdenoVerse platform, which uses gorilla adenovectors to generate durable immune responses against HPV-infected cells. This technological validation could have ripple effects across their pipeline, potentially accelerating development in other indications and enhancing partnership opportunities.

Regulatory Affairs Expert

The FDA's acceptance of Precigen's BLA with priority review for PRGN-2012 represents a significant regulatory achievement that substantially accelerates the potential approval timeline. This designation, reserved for therapies that would provide significant improvements in treating serious conditions, reduces the review period from 10 to 6 months, positioning PRGN-2012 for potential approval by August 27, 2025.

The FDA's decision not to convene an advisory committee is particularly telling. This suggests regulators view the benefit-risk profile as straightforward and the clinical data package as sufficiently robust to proceed without external expert input. Historically, this has been a positive indicator for approval prospects, though it doesn't guarantee success.

The regulatory package for PRGN-2012 is exceptionally strong, with multiple accelerated pathways engaged:

• The Breakthrough Therapy Designation provides enhanced FDA guidance and organizational commitment to expedited development
• The Orphan Drug Designation confers 7 years of market exclusivity upon approval, tax credits for clinical trials, and waiver of BLA user fees
• The accelerated approval pathway allows approval based on surrogate endpoints likely to predict clinical benefit

The Phase 1/2 data supporting this application is compelling for a rare disease therapy, with over 50% complete response rate and 85% reduction in surgical burden. These outcomes directly address the primary treatment goal for RRP patients – reducing or eliminating the need for repeated surgeries that cause cumulative laryngeal damage.

From a regulatory perspective, PRGN-2012 represents an interesting test case for the FDA's approach to novel gene therapies for rare diseases. The AdenoVerse platform's gorilla adenovectors are distinct from more common AAV-based gene therapies, potentially setting important regulatory precedents.

While the regulatory path appears favorable, potential challenges remain around manufacturing consistency and characterization – critical areas of focus for gene therapy reviews. Additionally, the FDA may require a post-approval Risk Evaluation and Mitigation Strategy (REMS) and long-term follow-up studies to monitor durability of effect and potential delayed adverse events, standard requirements for novel genetic medicines.

– Priority review reduces the BLA review timeline to 6-months and is granted to therapies that, if approved, would provide significant improvements in the treatment, diagnosis or prevention of serious conditions –

– If approved, PRGN-2012 would be the first and only available FDA-approved therapy for eligible patients with RRP, a rare and devastating chronic disease for which the current standard-of-care is repeated surgeries –

GERMANTOWN, Md., Feb. 25, 2025 /PRNewswire/ -- Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, today announced the US Food and Drug Administration (FDA) has accepted the company's biologics license application (BLA) for PRGN-2012 (nonproprietary name: zopapogene imadenovec^†), an investigational AdenoVerse^® gene therapy for the treatment of adults with recurrent respiratory papillomatosis (RRP). The FDA granted priority review to the BLA and set a Prescription Drug User Fee Act (PDUFA) target action date of August 27, 2025. The FDA has indicated that they are not currently planning to hold an advisory committee meeting to discuss this application.

PRGN-2012 is designed to elicit immune responses directed against cells infected with human papillomavirus (HPV) 6 or HPV 11. PRGN-2012 received Breakthrough Therapy Designation, Orphan Drug Designation, and an accelerated approval pathway from the FDA, and Orphan Drug Designation from the European Commission.

If approved, PRGN-2012 would be the first and only FDA-approved therapeutic for the treatment of adults with RRP. RRP is a rare, difficult-to-treat, lifelong neoplastic disease of the upper and lower respiratory tracts caused by infection with HPV 6 or HPV 11 that can be fatal. Currently, there is no cure for RRP and the current standard-of-care is repeated surgeries, which do not address the underlying cause of disease and are associated with significant morbidity. As a result, the cycle of recurrence and surgery continues and patients can require hundreds of lifetime surgeries.^1-7 The cumulative risk of laryngeal injury increases with each RRP surgery, particularly with patients requiring five or more lifetime surgeries.⁸ There is high unmet need for a therapeutic alternative to prevent these irreversible surgery-related injuries.

The BLA is supported by data from the pivotal Phase 1/2 clinical study (NCT04724980), which were presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting and published in The Lancet Respiratory Medicine. The pivotal study met its primary safety and efficacy endpoints, with more than 50% of patients achieving Complete Response and more than 85% of patients experiencing a decrease in surgical interventions in the year after PRGN-2012 treatment compared to the year prior to treatment. PRGN-2012 was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2. Primary endpoints included safety and Complete Response rate defined as the percentage of patients who require no RRP surgeries in the 12-month period after PRGN-2012 treatment completion. Key secondary endpoints included HPV-specific immune responses, extent of papilloma growth as measured by Derkay scoring, and quality of life as measured by Vocal Handicap Index-10 (VHI-10).

"The priority review designation is a testament to the FDA's recognition of the significant unmet need for the RRP patient population. 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," said Helen Sabzevari, PhD, President and CEO of Precigen. "Treatment with PRGN-2012 has shown significant, durable clinical benefit. 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. 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, estimated at more than 27,000 adults in the US, later this year." 

AdenoVerse®
Precigen's AdenoVerse platform utilizes a library of proprietary adenovectors for the efficient gene delivery of therapeutic effectors, immunomodulators, and vaccine antigens designed to modulate the immune system. Precigen's gorilla adenovectors, part of the AdenoVerse library, have potentially superior performance characteristics as compared to current competition. AdenoVerse gene therapies have been shown to generate high-level and durable antigen-specific T-cell immune responses as well as an ability to boost these responses via repeat administration. Superior performance characteristics and high yield manufacturing of AdenoVerse vectors leveraging UltraVector^® technology allows Precigen to engineer cutting-edge investigational gene therapies to treat complex diseases.

Precigen: Advancing Medicine with Precision^™
Precigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target the most urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit www.precigen.com or follow us on LinkedIn or YouTube.

Trademarks
Precigen, AdenoVerse, UltraVector and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.

Cautionary Statement Regarding Forward-Looking Statements
Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon the Company's current expectations and projections about future events and generally relate to plans, objectives, and expectations for the development of the Company's business, including the timing and progress of preclinical studies, clinical trials, regulatory approvals, commercial launches and related milestones, the promise of the Company's portfolio of therapies, and in particular its CAR-T and AdenoVerse therapies. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties and actual future results may be materially different from the plans, objectives and expectations expressed in this press release. The Company has no obligation to provide any updates to these forward-looking statements even if its expectations change. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For further information on potential risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in the Company's most recent Annual Report on Form 10-K and subsequent reports filed with the Securities and Exchange Commission.

Investor Contact:
Steven M. Harasym
Tel: +1 (301) 556-9850
investors@precigen.com 

Media Contacts:
Donelle M. Gregory
press@precigen.com 

Glenn Silver
Lazar-FINN Partners
glenn.silver@finnpartners.com 

^†zopapogene imadenovec is the nonproprietary name for the investigational therapeutic known as PRGN-2012. Zopapogene imadenovec has not been approved by any health authority in any country for any indication.

References
¹ Mounts, P et al. (1982). "Viral etiology of juvenile- and adult-onset squamous papilloma of the larynx." Proc Natl Acad Sci U S A 79(17): 5425-5429.
² Smith, E et al. (1993). "Human papillomavirus infection in papillomas and nondiseased respiratory sites of patients with recurrent respiratory papillomatosis using the polymerase chain reaction." Arch Otolaryngol Head Neck Surg 119(5): 554-557.
³ Derkay, CS et al. (2008). "Recurrent respiratory papillomatosis: a review." Laryngoscope 118(7): 1236-1247.
⁴ Derkay, CS et al. (2019). "Update on Recurrent Respiratory Papillomatosis." Otolaryngol Clin North Am 52(4): 669-679.
⁵ Seedat, RY (2020). "Juvenile-Onset Recurrent Respiratory Papillomatosis Diagnosis and Management - A Developing Country Review." Pediatric Health Med Ther 11: 39-46.
⁶ Dedo, HH et al. (2001). "CO(2) laser treatment in 244 patients with respiratory papillomas." Laryngoscope 111(9): 1639-1644.
⁷ Silver, RD et al. (2003). "Diagnosis and management of pulmonary metastasis from recurrent respiratory papillomatosis." Otolaryngol Head Neck Surg 129(6): 622-629.
⁸ So, RJ et al. (2024). "Factors Associated with Iatrogenic Laryngeal Injury in Recurrent Respiratory Papillomatosis." Otolaryngol Head Neck Surg 170:1091-1098.

 

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FAQ

When is the FDA's target decision date for Precigen's PRGN-2012 therapy for RRP?

The FDA has set a PDUFA target action date of August 27, 2025 for Precigen's PRGN-2012 therapy for recurrent respiratory papillomatosis (RRP).

What percentage of RRP patients achieved Complete Response in PGEN's PRGN-2012 clinical trial?

More than 50% of patients achieved Complete Response, defined as requiring no RRP surgeries in the 12-month period after PRGN-2012 treatment completion.

How many adult patients with RRP could potentially benefit from Precigen's PRGN-2012 therapy?

According to Precigen, the RRP patient population is estimated at more than 27,000 adults in the United States.

What special designations has PGEN's PRGN-2012 received from regulatory authorities?

PRGN-2012 has received Breakthrough Therapy Designation, Orphan Drug Designation, and an accelerated approval pathway from the FDA, plus Orphan Drug Designation from the European Commission.

How does PRGN-2012 work to treat recurrent respiratory papillomatosis compared to current treatments?

PRGN-2012 is designed to elicit immune responses against cells infected with HPV 6 or HPV 11, addressing the underlying cause of RRP, unlike the current standard-of-care which relies on repeated surgeries that only treat symptoms.

What was the reduction in surgical interventions for PGEN's PRGN-2012 patients in clinical trials?

More than 85% of patients experienced a decrease in surgical interventions in the year after PRGN-2012 treatment compared to the year prior to treatment.

What is the significance of priority review status for Precigen's PRGN-2012 BLA?

Priority review reduces the BLA review timeline to 6 months instead of the standard 10 months, and is granted to therapies that would provide significant improvements in treating serious conditions.