INO-3107 and the PAPZIMEOS precedent · INO-3107 · Aug 2025
What evidence did the FDA accept when it approved PAPZIMEOS?
One single-arm, open-label Phase 1/2 study, measured against each patient's own surgical history, with a novel endpoint built from patient input. The FDA calls this “significant regulatory flexibility”.
EphemerisX Research · Published · 1 source document · 2 min read
Short answer
A single study. The FDA's review summary says substantial evidence of effectiveness came from one single-arm, open-label Phase 1/2 trial, with each patient's surgeries after treatment compared with their own baseline, and a complete-response endpoint (no surgery for 12 months) that the agency says it established from patient perspectives. It describes this as “significant regulatory flexibility”.
What the evidence shows
The study: The safety and effectiveness of PAPZIMEOS were evaluated in Study PRGN-2012-201 (NCT04724980), a single-arm, open-label Phase 1/2 study in patients with RRP requiring three or more surgical procedures per year
FDA · Aug 14, 2025 · p. 5. The comparison was within each patient: The number of surgical interventions following treatment was compared to a patient’s baseline (intra-patient baseline control) to evaluate a clinically meaningful treatment effect
FDA · Aug 14, 2025 · p. 5.
The result: The primary endpoint, complete response (CR) rate at 12 months, defined as the percentage of subjects with no clinically indicated surgical interventions during the 12 months following treatment, was achieved in 51% of patients (18/35; 95% CI 34% to 69%)
FDA · Aug 14, 2025 · p. 5, and 15 patients maintained complete response at 2 years yielding a 24-month complete response rate of 43% (15/35; 95% CI 26% to 61%)
FDA · Aug 14, 2025 · p. 5.
The FDA's conclusion: Substantial evidence of effectiveness is demonstrated in Study PRGN-2012-201, a single adequate and well-controlled trial with confirmatory evidence
FDA · Aug 14, 2025 · p. 5.
How it got there: the Agency exercised significant regulatory flexibility in the review of this BLA
FDA · Aug 14, 2025 · p. 6. The Agency incorporated patient perspectives to establish a novel endpoint which allowed a single pivotal study with change from baseline control design and small sample size to be considered as an adequate and well-controlled trial to support this BLA
FDA · Aug 14, 2025 · p. 6. Elsewhere the summary gives the reason: RRP's rarity and the impracticality of placebo-controlled designs given the current surgical standard of care
FDA · Aug 14, 2025 · p. 17.
The application was not taken to an advisory committee: the submitted information did not raise unresolved scientific or regulatory questions that would benefit from advisory committee discussion
FDA · Aug 14, 2025 · p. 17. The FDA's Summary Basis for Regulatory Action for PAPZIMEOS does not mention INO-3107, INOVIO or electroporation. FDA · searched What the approval type became: How did PAPZIMEOS go from an accelerated-approval application to a traditional approval?
Follow the thread
- How did PAPZIMEOS go from an accelerated-approval application to a traditional approval?“Significant regulatory flexibility”
- How do INOVIO and Precigen describe each other's product?The FDA's review does not mention INO-3107
- 51% vs. 28.1%: the FDA decision behind two RRP treatmentsPAPZIMEOS's single-arm study
The documents, by date
The passages quoted
FDA Summary Basis for Regulatory Action, August 14, 2025
The FDA's Summary Basis for Regulatory Action for PAPZIMEOS does not mention INO-3107, INOVIO or electroporation.
Open the document →FDA Summary Basis for Regulatory Action, August 14, 2025 · page 5
The number of surgical interventions following treatment was compared to a patient’s baseline (intra-patient baseline control) to evaluate a clinically meaningful treatment effect.Open at the source →
FDA Summary Basis for Regulatory Action, August 14, 2025 · page 5
The primary endpoint, complete response (CR) rate at 12 months, defined as the percentage of subjects with no clinically indicated surgical interventions during the 12 months following treatment, was achieved in 51% of patients (18/35; 95% CI 34% to 69%). Furthermore, 15 patients maintained complete response at 2 years yielding a 24-month complete response rate of 43% (15/35; 95% CI 26% to 61%).Open at the source →
FDA Summary Basis for Regulatory Action, August 14, 2025 · page 5
Substantial evidence of effectiveness is demonstrated in Study PRGN-2012-201, a single adequate and well-controlled trial with confirmatory evidence, demonstrating a clinically meaningful observed complete response rate at 12 months and durability of response through 2 years.Open at the source →
FDA Summary Basis for Regulatory Action, August 14, 2025 · page 5
The safety and effectiveness of PAPZIMEOS were evaluated in Study PRGN-2012-201 (NCT04724980), a single-arm, open-label Phase 1/2 study in patients with RRP requiring three or more surgical procedures per year. In this study, eligible adults with a confirmed RRP diagnosis first underwent surgical debulking before receiving four subcutaneous injections of PAPZIMEOS on days 1, 15, 43, and 85.Open at the source →
FDA Summary Basis for Regulatory Action, August 14, 2025 · page 6
Acknowledging the rarity and serious life-threatening nature of RRP, the Agency exercised significant regulatory flexibility in the review of this BLA. The Agency incorporated patient perspectives to establish a novel endpoint which allowed a single pivotal study with change from baseline control design and small sample size to be considered as an adequate and well-controlled trial to support this BLA.Open at the source →
FDA Summary Basis for Regulatory Action, August 14, 2025 · page 17
The submitted information, including clinical study design and trial results, did not raise unresolved scientific or regulatory questions that would benefit from advisory committee discussion. Therefore, this BLA was not referred to the Cellular, Tissue, and Gene Therapies Advisory Committee.Open at the source →
FDA Summary Basis for Regulatory Action, August 14, 2025 · page 17
Most notably, FDA accepted a single-arm, open-label Phase 1/2 study as a single adequate and well controlled study with confirmatory evidence for licensure due to RRP's rarity and the impracticality of placebo-controlled designs given the current surgical standard of care.Open at the source →