PolyPid Publishes Phase 3 SHIELD I Trial Results on D-PLEX₁₀₀ in Preventing Abdominal Surgery Infections

PolyPid Ltd., a biopharmaceutical company focused on improving surgical outcomes, recently announced the publication of a study in the International Journal of Surgery. The study, entitled "Effect of Local Prolonged-Release Incisional Doxycycline on Surgical Site Infection Prophylaxis in Abdominal Colorectal Surgery: The SHIELD I Randomized Clinical Trial", details the findings from the Phase 3 SHIELD I trial. This trial is one of the largest conducted in over ten years on the prevention of surgical site infections (SSIs) in colorectal resection.

The SHIELD I trial aimed to evaluate the efficacy and safety of D-PLEX100, a prolonged-release doxycycline formulation, in preventing SSIs when used alongside standard care (SoC) which includes systemic antibiotics. The study was conducted across more than 60 centers in the United States, Europe, and Israel, enrolling a total of 977 patients. The participants were randomly assigned to receive either D-PLEX100 in addition to SoC or SoC alone. The trial's primary endpoint was the occurrence of incisional SSIs or the necessity for incisional reinterventions within 30 days post-surgery.

Results showed that the overall infection rate in SHIELD I was influenced by COVID-19-related safety restrictions, which complicated the achievement of the primary endpoint. Despite this, further analyses indicated that D-PLEX100 might benefit patients at higher risk of SSIs, particularly those with long surgical incisions. Specifically, for incisions longer than 20 cm, a significant 54% reduction in SSI rates was observed in the treatment group compared to the control group.

Emeritus Professor Charles E. Edmiston highlighted the substantial cost of SSIs to healthcare payers and emphasized the ongoing need for effective SSI prevention measures. The SHIELD I study's publication comes at a time when infection rates are normalizing to pre-pandemic levels, and the findings suggest that D-PLEX100 could be an important component of future surgical care strategies.

PolyPid's CEO, Dikla Czaczkes Akselbrad, expressed optimism about the results and noted that the final patient for the SHIELD II trial had recently been enrolled. This ongoing Phase 3 trial focuses on patients with large surgical incisions and is expected to yield top-line results in the first quarter of 2025.

In terms of safety, SHIELD I indicated no significant concerns, with the occurrence of treatment-emergent adverse events (TEAEs) being similar between the D-PLEX100 and SoC groups. Notably, severe or serious TEAEs and the necessity for surgical reinterventions were numerically lower in the D-PLEX100 group.

D-PLEX100, utilizing PolyPid’s PLEX technology, aims to deliver localized, controlled, and prolonged release of doxycycline at the surgical site, maintaining high drug concentration for up to 30 days. This approach is designed to prevent SSIs, including those caused by antibiotic-resistant bacteria. The product has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration for preventing SSIs in patients undergoing elective colorectal surgery.

PolyPid continues to advance its clinical programs with the aim of enhancing surgical outcomes and addressing unmet needs in SSI prevention. Alongside D-PLEX100, the company is also exploring the potential of OncoPLEX, a preclinical candidate for treating solid tumors such as glioblastoma.