FDA Priority Review for Precigen’s PRGN-2012: Promising Treatment for Adult Respiratory Papillomatosis by August 2025

FDA Grants Priority Review to Precigen’s PRGN-2012 for Recurrent Respiratory Papillomatosis

The U.S. Food and Drug Management (FDA) has accepted precigen, Inc.’s biologics license application (BLA) for PRGN-2012 (zopapogene imadenovec^†), an investigational gene therapy aimed at treating adults suffering from recurrent respiratory papillomatosis (RRP). This acceptance includes a priority review, setting the Prescription drug User Fee Act (PDUFA) target action date for Aug. 27, 2025.

Why This Matters: RRP is a rare and debilitating chronic disease characterized by the growth of papillomas (tumors) in the respiratory tract, primarily the larynx. These growths can cause breathing difficulties, hoarseness, and other serious complications.Current treatment primarily involves repeated surgeries to remove the papillomas, which can be invasive, risky, and don’t address the underlying cause ³.

Understanding Recurrent Respiratory Papillomatosis (RRP)

RRP is primarily caused by human papillomavirus (HPV) types 6 and 11 ¹². These viruses induce the growth of papillomas that can obstruct the airway. While RRP can occur in both children and adults, the juvenile-onset form tends to be more aggressive ⁵. The constant recurrence of papillomas necessitates repeated surgical interventions, often involving CO2 laser treatments ⁶.Though, these surgeries can lead to scarring and, in certain specific cases, pulmonary metastasis ⁷.

• Etiology: HPV 6 and 11 are the primary causative agents.
• Symptoms: Hoarseness, breathing difficulties, and chronic cough.
• Current Treatment: Primarily surgical removal, frequently enough with laser therapy.
• Complications: Scarring, pulmonary metastasis, and iatrogenic laryngeal injury ⁸.

PRGN-2012: A Novel Approach

PRGN-2012 is designed to stimulate immune responses against cells infected with HPV 6 or HPV 11. By targeting the underlying viral infection, this gene therapy aims to provide a more durable solution compared to surgery alone.

The FDA has already granted PRGN-2012 several key designations:

• Breakthrough Therapy Designation
• Orphan Drug Designation (U.S. and European Commission)
• Accelerated Approval Pathway

Expert Insight

“The priority review designation is a testament to the FDA’s recognition of the critically important unmet need for the RRP patient population. RRP patients have never had an FDA-approved therapy, relying rather on repeated surgeries to alleviate the symptoms of RRP without addressing the underlying disease,” said Helen Sabzevari, PhD, President and CEO of precigen.

Sabzevari further noted, “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 option 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® Platform: The Technology Behind PRGN-2012

PRGN-2012 utilizes precigen’s AdenoVerse® platform,which employs a library of proprietary adenovectors for efficient gene delivery. These vectors are designed to modulate the immune system by delivering therapeutic effectors, immunomodulators, and vaccine antigens. This platform allows for the generation of high-level and durable antigen-specific T-cell immune responses, with the ability to boost these responses through repeat administration. The platform’s superior performance characteristics and manufacturing leveraging UltraVector® technology enable the engineering of investigational gene therapies for complex diseases.

Implications and Future Directions

If approved, PRGN-2012 would represent a paradigm shift in the treatment of RRP, moving away from repetitive surgical interventions towards a therapy that targets the root cause of the disease. This could significantly improve the quality of life for thousands of adults affected by RRP in the United States.

Conclusion

The FDA’s priority review of PRGN-2012 offers a beacon of hope for individuals battling recurrent respiratory papillomatosis. With a PDUFA target action date set for Aug. 27, 2025, the coming months will be crucial as Precigen works with the FDA to perhaps bring the first approved therapeutic option to RRP patients. For more information about Precigen and their innovative work, visit www.precigen.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.

What could be some of the unintended consequences that might arise from the widespread use of gene therapies like PRGN-2012?

Archyde Interview: Dr. Eleanor Vance Discusses PRGN-2012 and the Future of Recurrent Respiratory Papillomatosis Treatment

The FDA’s recent priority review designation for Precigen’s PRGN-2012 is a significant step forward in the fight against Recurrent Respiratory Papillomatosis (RRP). To understand the implications of this development,Archyde News spoke wiht Dr. Eleanor Vance, Chief of Otolaryngology at the fictional Northwood Medical Center, a leading expert in RRP.

understanding the Meaning of PRGN-2012’s Priority Review

Archyde: Dr. Vance, thank you for joining us. Can you explain why the FDA’s priority review for PRGN-2012 is significant for the RRP community?

Dr. Vance: Absolutely. The priority review considerably accelerates the evaluation process of PRGN-2012. For a condition like Recurrent Respiratory Papillomatosis, where patients face repeated surgeries and the consequent risks, time is crucial. This designation signals the FDA’s recognition of the urgent need for a new, effective treatment option.

The Challenges of Current RRP Treatments

Archyde: What are the current limitations of treating RRP, and how does PRGN-2012 possibly address these?

Dr. Vance: Currently, the primary treatment for RRP involves surgical removal of papillomas, often using CO2 lasers. While effective in managing symptoms, these surgeries are invasive, carry risks like scarring and laryngeal injury, and, most importantly, don’t prevent recurrence. PRGN-2012, as a gene therapy, aims to stimulate the immune system to target the underlying HPV infection, potentially offering a more durable solution and reducing the need for repeated interventions.

How PRGN-2012 Works: Targeting the Root Cause of RRP

Archyde: Could you elaborate on the mechanism of action of PRGN-2012? How does it differ from existing approaches?

Dr. vance: PRGN-2012 utilizes precigen’s AdenoVerse® platform to deliver genetic material that stimulates an immune response against HPV 6 and HPV 11, the viruses responsible for RRP in most cases.Unlike surgery, wich only removes the visible papillomas, PRGN-2012 aims to address the viral infection causing the growths. This approach could potentially lead to long-term remission and a significant improvement in patients’ quality of life.

The Impact on Patient Care

Archyde: If approved, how do you envision PRGN-2012 changing the standard of care for RRP patients?

Dr. Vance: The impact would be substantial. RRP patients often face a relentless cycle of surgeries every few months. PRGN-2012 offers the hope of breaking that cycle.It could dramatically reduce the physical and emotional burden on patients, minimize the risks associated with repeated surgeries, and potentially prevent long-term complications linked to the disease and its treatment.

Looking Ahead: Challenges and Future Directions

Archyde: What are some of the challenges that remain, even with the potential approval of PRGN-2012?

Dr.Vance: while promising, gene therapies are still relatively new, and long-term data is needed to fully assess the durability of PRGN-2012’s effects. Furthermore, accessibility and cost will be important considerations.Ensuring that this potentially life-changing treatment is available to all patients who could benefit will be crucial. We also need to continue research into RRP to explore other therapeutic avenues and preventative strategies.

A Thought-Provoking Question for Our Readers

Archyde: Dr. Vance, thank you for your insightful comments. a question for our readers: What impact do you think innovative therapies like PRGN-2012 will have on the future of treating rare and chronic diseases, and what steps can be taken to ensure equitable access to these advancements?

Dr. Vance: Thank you. It’s been a pleasure speaking with you.