Outer-Membrane Protein Targeting Antibiotics (OMPTAs) - New hope against antibiotic resistance

Important step forward for nosocomial pneumonia treatment

(PresseBox) ( Vienna, Austria, )
Polyphor today presented promising data for their novel class of antibiotics, the Outer Membrane Protein Targeting Antibiotics (OMPTA). This is the first new class of antibiotic against Gram-negative pathogens to reach advanced clinical development in over 40 years. Murepavadin (POL7080), the first member of the OMPTA class - currently in Phase II and soon expected to enter Phase III - is being developed for the treatment of the most severe Pseudomonas aeruginosa (PA) infection - nosocomial pneumonia (including hospital-acquired and ventilator-associated pneumonia) - a disease with a death rate of 20-50%.1

Early initiation of effective antimicrobial treatment for PA pulmonary infections is critical and a strong predictor of mortality.2 However, multi-drug resistant (MDR) PA has become a global problem and, as such, treatment is becoming more challenging with limited options available. Murepavadin, by means of its novel and unique mechanism of action, is extremely active and is being developed as first line treatment for MDR cases.

Dr Ignacio Martin-Loeches, St James' Hospital, Trinity College, Dublin (Ireland) explained, "PA represents a significant threat to the most vulnerable hospital patients, including intensive care patients, those with depleted immune systems such as those with cancer, people with severe burns and premature babies in neonatal units. Treatment options are limited and so this new class of antibiotics is desperately needed."

Data presented today at the 27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) have shown a high rate of clinical cure (91%) and low rate of mortality (9%) at day 28 in a small patient group (12 patients), when treated with Murepavadin.3 They also demonstrated that multiple doses of Murepavadin were considered to be safe and with acceptable tolerability.3

"Antibiotic resistance is one of the most serious health threats of our time with significant global implications. New treatment options are urgently needed", highlighted Prof. Antoni Torres, Respiratory Institute Hospital Clinic, Barcelona (Spain). "Today's announcement that Murepavadin has shown positive benefits in the trials offers hope for the management of this challenging patient group."

Dr Glenn Dale, Head of Early Development, Antimicrobials, Polyphor added, "Murepavadin's single pathogen focus prevents a build-up of resistance against other pathogens, which is a common problem with antibiotics. Today's findings show that our proposed dose of Murepavidin could be a promising new antimicrobial to treat PA.4 This year, we expect Murepavadin to enter Phase III trials and take another step to bring it to patients. In addition, our OMPTA platform could bring further new important therapies in the treatment of Gram-negative pathogens."

References

1. Zhang Y, et al. Mortality attributable to carbapenem-resistant Pseudomonas aeruginosa bacteremia: a meta-analysis of cohort studies. Emerg Microbes Infect. 2016. Available here: http://www.nature.com/emi/journal/v5/n3/full/emi201622a.html (accessed 20 April 2017).

2. Micek ST, et al. An international multicenter retrospective study of Pseudomonas aeruginosa nosocomial pneumonia: impact of multidrug resistance. Crit Care. 2015;19:219.

3. Armaganidis A, et al. Pharmacokinetic and efficacy analysis of Murepavadin (POL7080) co-administered with standard-of-care (SOC) in a Phase II study in patients with ventilator associated pneumonia (VAP) due to suspected or documented Pseudomonas aeruginosa infection. Poster 1308, ECCMID 2017.

4. Machacek M, et al. Population pharmacokinetics modeling of Murepavadin (POL7080) and simulation of target attainment in a population with ventilator-associated pneumonia due to infection with Pseudomonas aeruginosa. Poster 1307, ECCMID 2017.
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