POSITIVE RESULTS

PolyPid's D-PLEX100 hits primary endpoint in Phase 3 SSI prevention trial

The SHIELD II trial met its composite infection endpoint and cut surgical site infections 60% versus standard of care alone, backing an NDA now awaiting FDA acceptance.

PolyPid's Phase 3 SHIELD II trial of D-PLEX100 met its primary composite endpoint for preventing surgical site infection after large abdominal incisions and showed a 60% relative risk reduction on a secondary infection-rate endpoint.

By AppliedXLJuly 21, 2026Trial NCT04411199

Executive Summary

PolyPid's Phase 3 trial of D-PLEX100 met its primary composite endpoint for preventing infection after large abdominal incisions, and the company reported a substantial relative reduction in surgical site infections on a secondary measure.
The result supports a New Drug Application PolyPid has already filed with the FDA, positioning D-PLEX100 as a topical antibiotic-releasing adjunct to standard surgical prophylaxis rather than a replacement for it.
PolyPid signed a commercialization partnership with Azurity Pharmaceuticals tied directly to the trial result, with a U.S. launch targeted for early 2027 contingent on FDA acceptance of the filing.
The disclosed effect size on the secondary endpoint is presented as a relative reduction rather than paired with the underlying event counts in each arm, which limits how precisely the benefit can be sized from the current disclosure.
The trial's completion slipped repeatedly over more than three years before topline data posted, a pattern that shaped how long the readout took to arrive but does not change what the completed trial showed.

The result

PolyPid Ltd. said its 975-patient Phase 3 SHIELD II trial (NCT04411199) achieved its primary endpoint, a composite measure of surgical site infection, re-intervention, or death within 30 days of surgery in patients with abdominal incisions longer than 20 cm. On a secondary endpoint tracking the standalone surgical site infection rate, the company reported a 60% relative risk reduction versus standard of care alone, with a p-value of 0.0013. The trial compared D-PLEX100, added to standard antibiotic prophylaxis, against standard of care alone in patients undergoing elective colorectal resection. NCT04411199+1

How it was done

SHIELD II is a randomized, triple-masked, two-arm Phase 3 trial that enrolled 975 patients across 58 sites in 13 countries, including the United States, Germany, Poland, and Israel. Patients were randomized to D-PLEX, a topical antibiotic-releasing formulation, plus standard-of-care antibiotic prophylaxis, or to standard of care alone. The trial followed patients for 30 days post-surgery to assess the composite primary endpoint and secondary infection-rate measures, with an unblinded interim analysis planned once roughly 400 patients completed follow-up. The FDA had required a protocol revision in 2023, narrowing enrollment to patients with incisions over 20 cm following a Type D meeting. NCT04411199+1

What the disclosure withholds

The secondary-endpoint figure PolyPid highlighted, a 60% relative risk reduction, describes proportional change rather than the absolute infection rates in each arm. That framing was flagged in the underlying disclosure record as presenting a relative-only result, and the trial's own safety profile from the readout was not characterized in the announcement. Registry-level adverse event data collected separately show serious adverse events occurred in 75 of 481 patients in the D-PLEX plus standard-of-care arm and 85 of 493 in the standard-of-care-alone arm over a 60-day window, with 10 and 19 deaths recorded respectively. PolyPid+1

Timeline

The trial's primary completion date moved three times: from an original March 2022 target to March 2023, then to July 2024, and finally to March 2025, before the trial completed on April 14, 2025. Enrollment also fluctuated, dropping from a 900-patient target to 624 in October 2023 after the FDA-directed protocol narrowing, before the final analyzed population settled at 975. PolyPid had guided to mid-2024 topline results as far back as May 2023, and the readout posted roughly two years after that guidance window closed. NCT04411199+1

Regulatory and commercial path

PolyPid said it has completed an NDA submission to the FDA, with acceptance expected in August 2026 and a U.S. launch targeted for the first quarter of 2027. The company also entered an exclusive commercialization agreement with Azurity Pharmaceuticals covering the U.S. and Canada, under which Azurity will fund additional label-expansion trials beyond the abdominal surgery indication. PolyPid retains manufacturing rights worldwide and commercial rights outside the U.S. and Canada. PolyPid

Competitive context

Surgical site infection prevention has no drug approved specifically for this indication in the roster of FDA-approved options reviewed; ertapenem, an injectable penem antibiotic, is approved for treating established complicated intra-abdominal infections rather than preventing surgical site infections. Most trials in the same-drug competitive landscape screened for D-PLEX100 test antiseptics, wound-management devices, or oxygen-delivery systems rather than antibiotic-releasing implants, leaving D-PLEX100 without a direct same-mechanism, same-purpose comparator in this specific prevention setting.

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.