Peptidomimetic antibiotic · Pseudomonas
An experimental antibiotic designed to kill Pseudomonas aeruginosa, a hospital germ that often resists standard drugs. It is a cyclic peptidomimetic modeled on protegrin I, a natural antimicrobial peptide, and was developed by Polyphor (code POL7080) for pneumonia in hospitalized and ventilated patients.
Unlike many antimicrobial peptides, murepavadin does not punch holes in bacterial membranes. Its target is LptD, part of the machinery that carries lipopolysaccharide (LPS) out to the surface of Pseudomonas. With LPS transport disrupted, the bacterium cannot properly build its protective outer membrane. The drug is highly selective: in laboratory studies it was potent against Pseudomonas, including carbapenemase-producing and colistin-resistant strains, but largely inactive against other Gram-negative and Gram-positive species. Such a narrow, pathogen-specific spectrum is unusual for an antibiotic.
In laboratory and animal work, the parent compound showed nanomolar activity against Pseudomonas and was effective in a mouse septicemia model1, and murepavadin was active against multidrug-resistant isolates and in animal infection models3. In humans, a phase 1 study in healthy men found predictable, dose-proportional pharmacokinetics, mostly mild and short-lived adverse events, and no dose-limiting toxicity2. Its pharmacokinetics were also characterized in people with kidney impairment and in patients with ventilator-associated pneumonia3. Two phase 3 trials of the intravenous form, in ventilator-associated and other hospital-acquired Pseudomonas pneumonia, began in 2018; both were terminated in July 2019, with the registry giving a review of adverse-event data as the reason4,5. An inhaled form has since been described as in development for chronic lung infection in cystic fibrosis6.
Not approved by the FDA, and we found no approval by any other regulator. Its intravenous phase 3 trials were halted in 2019.
Human data are limited. In healthy volunteers, adverse events were mostly mild and short-lived2. The two phase 3 pneumonia trials were stopped early after a review of their adverse-event data, and we did not find posted or published results from them4,5. With no approved label, the side-effect profile in patients remains poorly defined.
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