AR-105 for Ventilator-Associated Pneumonia Does Not Meet Primary Endpoint

Aridis Pharmaceuticals announced results from the Company's first-in-patient Phase 2 clinical trial evaluating AR-105, a fully human IgG1 monoclonal antibody for the treatment of ventilator-associated pneumonia (VAP) caused by gram-negative Pseudomonas aeruginosa (P. aeruginosa). The recently completed study did not meet its primary endpoint of demonstrating superiority in Clinical Cure rates on Day 21 compared to placebo. Furthermore, there was a statistically significant imbalance in all-cause mortality, as well as Serious Adverse Event (SAE) rates between treatment groups that favored placebo. However, no SAE or mortality in the study was deemed to be drug related by the study investigators or the study's Data Monitoring Committee. At this point, the Company will no longer allocate further development resources to AR-105.

"Our team is analyzing the full data set to better understand these top-line results and report the final analysis as soon as possible. We wish to extend our appreciation to the patients, their families, and investigators for their contribution to the study," said Wolfgang Dummer, M.D., Ph.D., Chief Medical Officer of Aridis Pharmaceuticals.

"I want to underscore our gratitude for efforts of the investigators, patients, and families from which a substantial body of data has been generated that will guide further development of anti-infective immunotherapies," said Vu Truong, Ph.D., Chief Executive Officer of Aridis Pharmaceuticals. "Moving forward, we remain enthusiastic about and will re-focus on the balance of our robust pipeline including AR-301 and AR-501 which are both in clinical development. Our lead antibody, AR-301, targets gram-positive S. aureus alpha-toxin and is currently in Phase 3 global clinical development for the treatment of VAP. This trial is progressing on track, and we look forward to reporting interim data in the first half of 2020 as well as the subsequent top-line data in late 2020."

The AR-301 Phase 3 trial, which was initiated in the first quarter of 2019, is actively enrolling in approximately 240 clinical centers in 20 countries. Participating centers in all countries are following a single stringent clinical protocol and standard of care procedures for critically ill VAP patients. The trial represents the first ever Phase 3 superiority clinical study evaluating immunotherapy with a fully human monoclonal antibody for the treatment of acute pneumonia in the intensive care unit (ICU) setting.

AR-301 is a fully human monoclonal IgG1 antibody that was derived from our proprietary MabIgX® platform technology, specifically targeting gram-positive S. aureus alpha-toxin, which is a secreted toxin well-known as being central and indispensable to the pathogenesis of this bacteria. It has been shown in vitro to protect against alpha-toxin mediated destruction of host cells, thereby potentially preserving the human immune response. AR-301's anti-toxin target and mode of action are different from AR-105's cell surface carbohydrate target and mode of action, and is independent of the antibiotic resistance profile of S. aureus. Additional external validation of targeting S. aureus alpha-toxin has also been obtained from AstraZeneca's MEDI-4893, another monoclonal antibody against this epitope, which is in development for the prophylaxis of S. aureus VAP.

The development of AR-105, a mAb targeting a cell surface carbohydrate (alginate) on P. aeruginosa, was based on animal models of acute pneumonia, sepsis and keratitis which supported its usage as both a therapeutic and prophylactic therapy. Focusing on AR-105's therapeutic use, a Phase 1 dose-ranging, clinical trial was conducted involving 16 healthy adult volunteers who received up to a 20 mg/kg IV dose of this agent. In this study, AR-105 was shown to be safe and well tolerated and exhibited a plasma half-life of approximately 21 days. This trial informed the choice of both the dose (20 mg/kg) and schedule (one IV injection) for the Phase 2- trial.

The Phase 2 trial, which was initiated in the second quarter of 2017, was a randomized, double blinded, placebo controlled, superiority study which treated 158 VAP patients in 53 clinical sites from 13 countries across the U.S., Europe and Asia. Patient enrollment was based on admittance to an intensive care unit for pneumonia caused by P. aeruginosa bacteria as determined using a rapid diagnostic and/or culture test. Such VAP patients were randomized in a 1:1 fashion to receive either standard-of-care antibiotic therapy with placebo (placebo arm) or standard-of-care antibiotic therapy in addition to AR-105 (experimental arm). The treatment regimen was a single intravenous infusion (IV) of either AR-105 at a dose of 20 mg/kg or placebo. The primary endpoint of this trial was clinical cure of pneumonia at Day 21 post study drug treatment, as determined by the principal investigator. The trial was designed to demonstrate statistical superiority of AR-105 over standard-of-care. Secondary endpoints of the trial included clinical cure of pneumonia at Day 28, Day 14, or Day 7, all-cause mortality, and several health economics parameters.

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