PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: a pivotal phase 1/2 clinical trial.
Summary
In a single-arm phase 1/2 pivotal study (n=38; 35 at RP2D), PRGN-2012 achieved a 51% complete response rate—defined as no interventions required for 12 months—after adjuvant dosing post-surgical debulking, with a favorable safety profile. These results support regulatory submission as the first systemic therapy for adult RRP.
Key Findings
- Single-centre, single-arm phase 1/2 trial enrolled 38 adults with RRP; adjuvant PRGN-2012 dosed on days 1, 15, 43, and 85 post-debulking.
- At the recommended phase 2 dose (n=35), complete response rate (no intervention needed for 12 months) was 51%.
- Safety profile was favorable; results support a planned FDA biologics license application.
Clinical Implications
If approved, PRGN-2012 could reduce operative burden and airway morbidity by decreasing repeated surgical interventions in RRP. Centers should prepare for integration of adjuvant dosing schedules post-debulking and monitor long-term durability and safety.
Why It Matters
First-in-class systemic gene therapy demonstrating meaningful, durable clinical benefit in RRP, a rare disease lacking approved systemic treatments.
Limitations
- Single-arm, single-centre design without randomized comparator
- Short-to-intermediate follow-up; durability beyond 12 months not fully characterized
Future Directions
Randomized or external-controlled studies to confirm efficacy, durability, and safety; exploration of biomarkers predicting response; health-economic evaluations of surgical burden reduction.
Study Information
- Study Type
- Case series
- Research Domain
- Treatment
- Evidence Level
- III - Prospective single-arm interventional phase 1/2 trial without randomized control
- Study Design
- OTHER