Polyphor Halts Enrollment in Two Phase 3 Trials for Pneumonia Due to Safety Concerns

Pneumonia

Polyphor has temporarily halted enrollment for the pivotal Phase III trials PRISM-MDR and PRISM-UDR, which are evaluating murepavadin in patients with nosocomial pneumonia, due to higher than expected acute kidney injury incidences in the murepavadin arm of the PRISM-MDR trial. The kidney alteration incidences were observed in 56% of the patients treated in the PRISM-MDR study. According to literature and the comparator arm, an estimated incidence of 25-40% was expected. The decision to stop enrollment was made in conjunction with the independent Data Monitoring Committee. An update on the continuation of both Phase III studies will be provided in July once all data will be available and reviewed.

The decision to temporarily halt enrollment applies only to the PRISM-MDR and PRISM-UDR studies and does neither impact the further development of the murepavadin inhaled program, nor any of the other ongoing development programs.

PRISM-MDR is a multicenter, open label, randomized, active-controlled, parallel-group study focused on hospitals where multidrug resistant strains of Pseudomonas aeruginosa are frequent. The study will compare murepavadin combined with one other anti-pseudomonal antibiotic against two other anti-pseudomonal antibiotics. The study was designed based on feedback from the European Medicines Agency (EMA) and is agreed as the basis for a potential approval in the EU. The primary efficacy objective of the study is to assess the clinical cure rate at test of cure in the mITT population. The miTT population shall comprise 120 evaluable subjects (80 in the treatment arm) with VABP confirmed to be due to Pseudomonas aeruginosa.

PRISM-UDR is a global multicenter, sponsor blinded, randomized, active-controlled, parallel-group, non-inferiority study of murepavadin combined with ertapenem in adult patients with nosocomial pneumonia due to Pseudomonas aeruginosa. The primary efficacy objective is to demonstrate non-inferiority (20% non-inferiority margin) of murepavadin compared to an anti-pseudomonal β-lactam-based antibiotic. The study was designed based on feedback from the U.S. FDA and is agreed as the basis for a potential approval in the US. Eligible subjects with a high probability of nosocomial pneumonia due to Pseudomonas aeruginosa will be allocated at random to receive murepavadin or a comparator beta-lactam agent in a 1:1 ratio. The primary analysis population will comprise 210 subjects (105 subjects per arm) with nosocomial pneumonia confirmed to be due to Pseudomonas aeruginosa.

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About nosocomial pneumonia

Nosocomial pneumonia (also known as Hospital-acquired pneumonia) refers to any pneumonia contracted by a patient in a hospital at least 48–72 hours after being admitted. Pseudomonas aeruginosa is the second leading cause of nosocomial pneumonia, with a high mortality rate of 30-40%. Every year, Pseudomonas aeruginosa causes up to 250,000 hospital-acquired infections in the US and Europe alone; in the US, for example, it is responsible for 9% of all hospital-acquired infections.

About murepavadin

Murepavadin is a pathogen specific antibiotic functioning through a novel mechanism of action involving binding to an outer membrane protein of Pseudomonas aeruginosa. In contrast to commonly used broad-spectrum antibiotics, murepavadin is a precision medicine and as such it supports the growing practice known as “antibiotic stewardship” which, among other things, seeks to reduce the excessive use of broad-spectrum products to avoid the buildup of resistance and to preserve the microbiome of the patients.

The FDA has granted murepavadin Qualified Infectious Disease Product (QIDP) and fast track designation.