PDUFA Date

PolyPid's D-PLEX100 heads to FDA review with a PDUFA date near Q1 2027

The NDA rests on a completed 800-patient trial, Breakthrough Therapy and Fast Track status, and no approved drug yet prevents surgical site infection this way.

By AppliedXLJuly 13, 2026Trial NCT04411199

Executive Summary

PolyPid has moved its lead candidate into FDA review, guiding to a decision window in the first quarter of 2027 on whether a locally delivered antibiotic depot can prevent surgical site infection after colorectal surgery.
The application rests on a completed, multinational Phase 3 trial that finished enrollment and has already produced posted outcome data, not a program still awaiting its readout.
The candidate carries multiple FDA designations that signal the agency has already recognized the unmet need in this surgical population, ahead of any decision on the merits.
No competing program in surgical site infection shares this candidate's mechanism, leaving the field to answer whether local, sustained antibiotic release outperforms systemic prophylaxis alone.

The filing

PolyPid Ltd. started a rolling NDA submission for D-PLEX100 on March 30, 2026, with the Chemistry, Manufacturing and Controls and nonclinical modules submitted first and the clinical section expected to complete the filing. The company guided to a PDUFA target action date in the first quarter of 2027, to be confirmed once FDA accepts the application. In March 2026, FDA granted PolyPid a small-business waiver of the roughly $4.3 million PDUFA user fee for this NDA. PolyPid

The trial behind it

The filing rests on SHIELD II (NCT04411199), a Phase 3 trial in patients undergoing elective colorectal surgery with at least one abdominal incision longer than 20 centimeters. The trial enrolled 800 patients across sites in the United States, Israel, Germany, Poland, and ten other countries, and reached Completed status in June 2025 with a primary completion date of April 14, 2025. Its primary endpoint compared D-PLEX plus standard of care against standard of care alone on a composite treatment-failure measure: surgical site infection within 30 days, confirmed by a blinded adjudication committee, or death from any cause, in patients with a target incision longer than 20 centimeters. Posted results also cover secondary endpoints on infection rate in shorter incisions and on ASEPSIS wound-scoring, and an adverse-event comparison across both arms. NCT04411199

New data since completion

PolyPid presented additional ASEPSIS score analysis at the Surgical Infection Society's May 2026 annual meeting, reporting a 64% relative risk reduction, with a p-value of 0.0103, in the proportion of patients scoring above 20, the threshold the company describes for clinically significant wound infection. The company frames this as evidence that even among patients in the D-PLEX arm who experienced a wound event, severity was reduced. Separately, at the European Society of Clinical Microbiology and Infectious Diseases congress in April 2026, pharmacokinetic data described sustained, controlled release of doxycycline from D-PLEX100 for approximately 30 days with minimal systemic exposure. PolyPid

Regulatory signals

D-PLEX100 has accumulated Breakthrough Therapy, Fast Track, and Qualified Infectious Disease Product designations from FDA for this indication, each announced across multiple company disclosures between February 2024 and June 2025. These designations reflect FDA's acknowledgment of an unmet need in colorectal surgery infection prevention; they do not themselves predict the outcome of the pending NDA review.

The competitive field

No trial in surgical site infection prevention shares D-PLEX100's target or mechanism class, a locally delivered, sustained-release antibiotic depot placed at the incision site. The nearest comparators in the indication test chlorhexidine antisepsis, mupirocin, delafloxacin, and negative-pressure wound therapy, none of which share the same mechanism. Twelve trials in this indication have used a small-molecule modality, but PolyPid's approach of local depot delivery at the surgical site stands apart from systemic or topical antibiotic prophylaxis. Given no validated local-delivery mechanism has reached approval in this setting, an FDA decision that credits the completed trial's infection-rate data as sufficient for approval, without requiring further studies, would be the outcome that establishes this approach as a viable addition to standard surgical prophylaxis.

Trial timeline context

SHIELD II's primary completion date moved three times over the study's life, from March 2022 to March 2023, then to July 2024, then to March 2025, before the trial completed in June 2025. Enrollment also shifted, briefly rising to a target of 1,400 in mid-2020 before settling at 900 and finishing with 800 patients actually enrolled. The trial ultimately completed with a enrollment count close to its long-standing target, and the multi-year slippage in completion date predates the current NDA filing rather than bearing on it. NCT04411199

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.