Peptilogics Reports Positive 180-Day Top-Line Interim Data From Phase 1B Trial of PLG0206 in Patients With Periprosthetic Joint Infection (PJI)

2023-09-19

临床结果快速通道临床1期孤儿药

In both patient cohorts followed for six months after PLG0206 treatment, there were: No treatment-related serious adverse events and, No recurrence was observed in 13 of 14 (93%) treated patients at Day-180 in contrast to reported 180-day success rate of 45%. PITTSBURGH--(BUSINESS WIRE)-- Peptilogics, a clinical-stage biotechnology company, today announced new top-line interim data for PLG0206 in periprosthetic joint infection (PJI) patients from their ongoing Phase 1b trial. At 180-days following treatment with PLG0206 administered during a DAIR (Debridement, Antibiotics, and Implant Retention) surgery, no treatment-related serious adverse events were reported in either cohort. One recurrence was observed in the trial (one of 14 patients, 7%), which was in the Low Dose cohort at Day-180; no recurrences were observed in the High-Dose cohort. This is significantly lower (p=0.029) than the 55% 180-day recurrence rate observed in a similar patient population reported by Zhu, et.al in the Journal of Arthroplasty in 2021. Detailed analyses will be presented at various conferences in the coming months. “I continue to be impressed with the results,” said Javad Parvizi, M.D., James Edwards Professor of Orthopedic Surgery, Rothman Institute at Thomas Jefferson University Hospital, and member of Peptilogics’ Clinical Advisory Board. “Most of the patients in this trial have a very high risk of failure due to their comorbidities including obesity, diabetes, and prior joint surgeries, making them some of the hardest patients to treat. To see such a significant reduction in recurrence in these patients within the 180-day period when we see most of the recurrences is truly remarkable. I look forward to using PLG0206 with PJI patients given the fit with my surgical workflow, and in other surgeries with high reinfection rates and comorbidities.” In the Phase 1b clinical trial, PLG0206 is being studied in patients undergoing DAIR for treatment of a PJI occurring after total knee arthroplasty (TKA). The trial is an open-label study that consisted of two seven-patient cohorts each that received either a single-dose escalating treatments of PLG0206 of 3 mg/mL or 10 mg/mL delivered as an irrigation during surgery. The results are compared to historical control patients that received the current standard-of-care consisting of saline and betadine irrigation during DAIR surgery. Due to the high prevalence of comorbidities and infection risk factors — 64% of the patients had two or more infection risk factors — enrolled patients had a 1.6–7-fold increased risk of infection, placing them among the most difficult-to-treat population of PJI patients. “I am very pleased to see these results — as an infectious diseases physician working closely with surgeons, I know how difficult it is to optimally dose and prescribe the right antibiotics for these patients without reliable culture information. We must always try to reduce recurrence of infection yet balance the use of high-dose systemic antibiotics with duration of use to limit short- and long-term harmful effects on these patients and the risk of developing antimicrobial resistance (AMR). Having a broad-spectrum tool at our disposal that can rapidly and empirically eliminate polymicrobial biofilms could fill an important and urgent unmet need in the treatment of PJI,” said Associate Professor Neel Shah, M.D., Director of Orthopedic Infectious Diseases Clinic, UPMC and member of Peptilogics’ Clinical Advisory Board. Jonathan Steckbeck, Ph.D., Chief Executive Officer of Peptilogics, added, “These results are promising and highlight the value PLG0206 could bring as a new treatment option for PJI. If these results hold in our upcoming pivotal trial, we can envision a future where DAIR surgeries could become the primary standard of care instead of 2-stage revision surgeries. This paradigm shift would dramatically reduce the number of surgeries per patient, long-term antibiotic usage, rehabilitation time and costs, and the socio-economic burden on the patients, which could lead to a better quality of life. By reducing the number of surgeries patients currently undergo to resolve PJI and the compounding cost effects of increased hospital visits and extended stays, and long-term aftercare attributed to PJI, PLG0206 can potentially reduce the financial burden on the overall healthcare system.” Mr. Steckbeck concluded, “With charges currently exceeding half a million dollars per patient and 40,000 patients in 2023 the overall burden of PJI on the healthcare system is over $20 billion and is only likely to keep increasing from here without new effective solutions. We have taken the first step toward providing a potentially curative solution to this debilitating condition.” Dr. Shah has a financial interest in Peptilogics. Disclaimer Research reported in this press release is supported by CARB-X. CARB-X’s funding for this project is provided in part with federal funds from the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority; under agreement number: 75A50122C00028, and by an award from Wellcome Trust (WT224842). The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of CARB-X or any of its funders. About PLG0206 PLG0206 is an investigational broad-spectrum, anti-bacterial and anti-biofilm peptide therapeutic currently in clinical development for the treatment of PJI. PLG0206 was designed with a unique mechanism of action that targets and disrupts bacterial membranes, allowing it to directly address the persistent bacterial pathogens within the biofilm that evade standard-of-care antibiotics. In both in vitro and in vivo non-clinical studies, PLG0206 has demonstrated best-in-class, rapidly bactericidal, broad-spectrum activity against a variety of pathogens including those identified by the World Health Organization and the Centers for Disease Control and Prevention as critical, urgent, or high-priority targets, regardless of resistance phenotype. PLG0206 has been granted Orphan Drug Designation for the treatment of PJI, has been designated as a Qualified Infectious Disease Product (QIDP), and has been granted Fast Track Designation by the US FDA. About Periprosthetic Joint Infection (PJI) More than seven million total joint replacements will be performed annually in the major markets (US, UK, EU, JP) by 2030. Following joint replacement, over 150,000 patients will develop a PJI, a serious life-threatening condition, which often necessitates continuous antibiotic usage, multiple high-risk surgical procedures, and implant removal requiring more than 300,000 surgeries with limited ability to resolve the infection. The current standard of care has up to a 60% failure rate, resulting in a substantial number of patient deaths, evidenced by a 25% five-year mortality rate. About Peptilogics Peptilogics engineers peptide therapeutic candidates to radically improve the treatment landscape for patients with life-threatening diseases. Through biological and pharmaceutical expertise, novel artificial intelligence algorithms, and purpose-built super-computing, Peptilogics is advancing an extensive therapeutic pipeline and accelerating discovery efforts at a pace and scale that was previously impossible. Peptilogics is backed by investors in life science and technology including Peter Thiel, Presight Capital, Founders Fund, CARB-X, and Cystic Fibrosis Foundation Cystic Fibrosis Foundation. For more information about Peptilogics, visit Peptilogics or follow the company on Twitter and LinkedIn.