Murepavadin
The first antibiotic aimed at a bacterial outer-membrane protein, stopped in phase 3 by kidney injury
Murepavadin is a ring-shaped, peptide-like antibiotic designed to kill one germ: Pseudomonas aeruginosa, a common cause of pneumonia in intensive care and of chronic lung infection in cystic fibrosis. It works by jamming LptD, a protein the bacterium uses to build its outer coat. Given into a vein it reached phase 3, but both trials were halted in 2019 because too many patients developed acute kidney injury. Its developer then turned to an inhaled version, which has been given only to healthy volunteers. It is not approved anywhere.
Used in human trials: 2.2 mg/kg, Single infusion, Intravenous (Study: kidney impairment pharmacokinetics, 32 people) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Gram-negative bacteria such as Pseudomonas aeruginosa wrap themselves in an outer membrane whose outside face is made of lipopolysaccharide. That layer keeps many antibiotics out and is one reason Pseudomonas resists so many drugs. The lipopolysaccharide is made inside the cell and carried to the surface by a chain of seven transport proteins; the last, LptD, sits in the outer membrane and inserts it. Murepavadin blocks LptD. Its makers described it as the first of a new class of outer-membrane protein-targeting antibiotics, killing Pseudomonas without bursting it the way older membrane-active peptides do.
It is a cyclic peptidomimetic, a ring of 14 amino acids, developed by the company Polyphor; one laboratory group describes it as a mimic of the body's own host-defence peptides. It is strikingly narrow: it acts on Pseudomonas species and not on other bacteria. In surveillance collections it was very potent: across 1,219 isolates from the US, Europe and China it inhibited 99% at 0.5 mg/L or less, four to eight times more active than colistin, and it kept that activity against 785 extensively drug-resistant isolates, including colistin-resistant ones.
In people, the first published data came from healthy volunteers. Single and repeated intravenous infusions in healthy men gave predictable, dose-proportional blood levels with a half-life of about 2.5 to 5.3 hours, mild transient side effects and no dose-limiting toxicity. A separate study gave one infusion to 32 people with normal or impaired kidney function and found that the kidneys clear much of the drug: exposure rose two- to two-and-a-half-fold with impairment and the half-life stretched from 7.7 to as long as 24 hours, so the authors called for dose adjustment.
The pivotal tests were two phase 3 trials in hospital-acquired and ventilator-associated pneumonia, PRISM-MDR and PRISM-UDR. In May 2019 Polyphor paused both after acute kidney injury appeared in 56% of murepavadin-treated patients in PRISM-MDR, against the 25 to 40% it had expected from the literature and the comparator arm, and in July it closed them. ClinicalTrials.gov lists both as terminated for safety data review, with 41 and 2 patients enrolled. No efficacy result from either trial has been published in the records read, and intravenous murepavadin has not been developed further.
The company's answer was to deliver the drug straight to the lungs, where Pseudomonas lives in cystic fibrosis, while keeping blood levels low. A 2023 review of inhaled antibiotics lists inhaled murepavadin as in development. In January 2023 Spexis, as Polyphor had been renamed, reported a first-in-human study in 39 healthy volunteers given single ascending inhaled doses: on preliminary blinded data it was well tolerated with no serious adverse events, less than 5% reached the bloodstream, and lung-lining fluid levels stayed above the concentration that inhibits most cystic fibrosis isolates for 24 hours. That report has not been followed by a published paper or a registered patient trial in the sources searched.
Laboratory work since then has filled in how Pseudomonas escapes it and how it might be combined. Resistance arises from mutations in genes that build or move lipopolysaccharide (lpxL1, lpxL2, bamA, lptD, msbA) and in pmrB, the same sensor behind colistin resistance, so cross-resistance between the two is possible; about 9% of French cystic fibrosis strains already had raised MICs. In mice and cell cultures it made tobramycin, amikacin, ciprofloxacin and beta-lactams kill better. It also activates human mast cells through the MRGPRX2 receptor. None of this changes its status: it is an unapproved drug whose only human data are healthy-volunteer and kidney-function studies, plus a stopped phase 3 programme.
Mechanism of Action
Murepavadin binds LptD, the outer-membrane protein that inserts lipopolysaccharide into the Pseudomonas outer membrane, so the bacterium cannot finish building its protective coat.
Blocks lipopolysaccharide transport
With LptD jammed, lipopolysaccharide cannot reach the outer leaflet, and the outer membrane loses integrity and triggers envelope stress.
Pseudomonas only
Its target is specific to Pseudomonas species, so it has no useful action on other bacteria.
Lets other antibiotics in
In laboratory and mouse studies the weakened membrane let beta-lactams, aminoglycosides and ciprofloxacin act more strongly.
Published Research
These are studies of murepavadin read from their PubMed abstracts: two phase 1 studies in people, one review, and the laboratory and mouse work on its activity, resistance and combinations. The phase 3 safety finding and the inhaled first-in-human study come from the developer's own press releases, which are listed in References and named where they are used.
Phase 1 in healthy men: single and multiple doses
In a placebo-controlled study with ten single-dose cohorts of six men and three multiple-dose cohorts, half-life ranged from 2.52 to 5.30 hours, clearance and volume were steady across doses, and exposure rose in proportion to dose. Adverse events were transient and mostly mild; no dose-limiting toxicity was found.
Kidney impairment raises exposure
32 people with normal, mildly, moderately or severely impaired kidneys each received one 2.2 mg/kg infusion over 3 hours. Total exposure was 2.0 to 2.5 times higher with impairment, clearance fell from 7.0 to 2.4-3.8 L/h, and half-life lengthened from 7.7 up to 24 hours. It was well tolerated; the authors say doses need adjusting for kidney function.
A new class in the pipeline
A review written while intravenous murepavadin was in phase 3 for Pseudomonas pneumonia summarises its discovery, non-lytic mechanism and activity against carbapenemase-producing and colistin-resistant strains, its effect in animal infection models, and pharmacokinetics in people with impaired kidneys and in ventilated patients.
Activity across three continents
Against 1,219 P. aeruginosa isolates from 112 centres, murepavadin's MIC50 and MIC90 were both 0.12 mg/L; it was four to eight times more active than colistin and polymyxin B and equally active on isolates from Europe, the US and China. Only 0.3% had MICs above 2 mg/L.
Extensively drug-resistant isolates
Against 785 extensively drug-resistant isolates from Europe and North America (2016-17), murepavadin inhibited 96.7% at 0.5 mg/L or less and was eight times more active than colistin, keeping its potency against isolates resistant to colistin, ceftolozane-tazobactam or tobramycin.
Cystic fibrosis isolates against 13 antibiotics
Among 414 genome-sequenced isolates from people with cystic fibrosis, murepavadin had MIC50 0.12 and MIC90 2 mg/L and the highest activity per weight of the 14 agents tested; no clonal cluster explained resistance.
Cystic fibrosis strains and resistance
MICs depended strongly on method (MIC50 0.125 mg/L by broth, 4 mg/L by agar) but held up in artificial sputum and lung surfactant. It killed 95% of strains within 1-5 hours at 32 mg/L. Laboratory-selected resistant mutants carried changes in lipopolysaccharide genes (lpxL1, lpxL2, bamA2, lptD, lpxT, msbA).
Activity in biofilms
In 53 cystic fibrosis isolates grown as biofilms, murepavadin's biofilm inhibitory concentrations were similar to colistin and tobramycin, and it had the lowest concentration needed to eradicate 90% of biofilms (64 mg/L); aztreonam did worst.
Reduced susceptibility in French cystic fibrosis strains
Of 230 strains from 12 French hospitals, 9.1% had MICs above 4 mg/L. Gene swaps confirmed that mutations in lpxL1, bamA and pmrB cut susceptibility 8- to 32-fold, and some pmrB changes also reduced susceptibility to colistin and tobramycin, the other inhaled antibiotics.
Cross-resistance with colistin
Pseudomonas selected for resistance to POL7080 carried mutations in the sensor gene pmrB; gene-expression and microscopy work pointed to lipopolysaccharide changes that reduce binding at the cell surface, a mechanism shared with colistin.
Lipid A changes behind resistance
In 496 clinical isolates and resistant mutants, murepavadin resistance went with deletions in lpxL1 and lpxL2 and less hexa-acylated lipid A, raising MICs from 0.5 to 2-4 mg/L; lipopolysaccharide from resistant mutants provoked weaker inflammatory responses in human monocytes.
Exposure needed in infected mice
In neutropenic mice with Pseudomonas lung infection, the unbound drug exposure relative to MIC (fAUC/MIC) predicted effect best: about 28 for a static effect and 40 for a tenfold kill, figures meant to guide human dose choice.
Opens the door for beta-lactams
Murepavadin damaged outer-membrane integrity and switched on the envelope stress response, which let more beta-lactam into the cell and increased killing; combined with ceftazidime-avibactam it slowed the emergence of resistance.
Boosts aminoglycosides
Murepavadin raised bacterial respiration and membrane potential, increasing uptake of tobramycin and amikacin; the murepavadin-amikacin pair killed synergistically in a mouse pneumonia model.
Boosts ciprofloxacin
Murepavadin increased ciprofloxacin inside Pseudomonas by suppressing drug efflux, and the combination was synergistic in an acute mouse pneumonia model.
Biofilms and combinations in resistant isolates
Against 50 multidrug-resistant clinical isolates, MIC50 and MIC90 were 0.25 and 0.5 mg/L. It was synergistic with colistin in every strain and with meropenem against carbapenemase producers, and all combinations inhibited biofilms synergistically, most of all with tobramycin.
Activates mast cells
Murepavadin triggered calcium release, degranulation and chemokine output in a human mast cell line through the MRGPRX2 receptor, and through its mouse counterpart caused degranulation and leakier blood vessels in mice, which knockout mice lacked.
Dosing Data
Murepavadin has no approved label and no treatment dose: the phase 3 trials were stopped and their doses are not stated in the abstracts read. This is the single amount a published human study states.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Murepavadin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: intravenous). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Murepavadin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Murepavadin stays intact once mixed.
How it is taken
As it was given in human studies: Intravenous (Single infusion; Study: kidney impairment pharmacokinetics, 32 people).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of 2.5–5.3 hours (single intravenous doses, healthy men); 7.7 hours in a renal study's normal-function group. After about five half-lives almost none is left.
How long the doses were given: Study: kidney impairment pharmacokinetics, 32 people: Infused over 3 hours.
When effects appear: unknown; no source on this page gives a time to effect for Murepavadin. Results reported in the studies are under Published Research.
Source: half-life: PMID 29437621; Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Acute kidney injury in 56% of murepavadin-treated patients in the PRISM-MDR phase 3 trial, against an expected 25-40%, which stopped the programme (Polyphor press release, May 9, 2019); Mild, transient adverse events in healthy volunteers, with no dose-limiting toxicity (PMID 29437621); Much higher blood levels when kidney function is reduced (PMID 30012756); Inhaled single doses in 39 volunteers: no serious adverse events on preliminary blinded data (Spexis press release, January 9, 2023). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Murepavadin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the human studies and the developer's reports”).
Interactions
Unknown: a PubMed search for human interaction studies of Murepavadin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Murepavadin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Murepavadin's expected mass, 1,553.8 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: In Clinical Trials (Not approved anywhere: Drugs@FDA and the EMA medicines list hold no record (searched October 29, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the human studies and the developer's reports.
Contraindications & Cautions
No label exists. These cautions follow from the evidence.
Legal Status
Murepavadin is not approved anywhere. Its intravenous phase 3 trials were terminated in 2019.
Frequently Asked Questions
?What is murepavadin?
A ring-shaped, peptide-like antibiotic that kills only Pseudomonas aeruginosa by blocking LptD, a protein the bacterium needs to build its outer membrane. It was developed by Polyphor, later renamed Spexis.
?Why was it stopped?
In 2019 its two intravenous phase 3 pneumonia trials were halted and then closed after acute kidney injury occurred in 56% of murepavadin-treated patients in one trial, more than the 25 to 40% expected.
?Is the inhaled form available?
No. A single-dose study in 39 healthy volunteers was reported by the company in January 2023; no patient trial or approval followed in the sources searched.
?Does it work on other bacteria?
No. Its target is specific to Pseudomonas, so it has no useful activity against other species.
?Can Pseudomonas become resistant to it?
Yes, in the laboratory and in some cystic fibrosis strains, through changes in lipopolysaccharide genes and in pmrB, which can also reduce susceptibility to colistin.
References
- [other] PubChem CID 91824766, Murepavadin: formula C73H112N22O16, molecular weight 1553.8. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/91824766
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT03409679 and NCT03582007 (phase 3, intravenous, terminated); NCT02096328 (phase 2, completed); NCT02897869 and NCT02110459 (phase 1, completed).
- [other] Polyphor AG, press release, May 9, 2019: enrolment temporarily halted in the phase III PRISM-MDR and PRISM-UDR studies of murepavadin after acute kidney injury in 56% of treated patients in PRISM-MDR, against an expected 25-40%. Read October 29, 2026 (reproduced by BioSpace). https://www.biospace.com/polyphor-temporarily-halts-enrollment-in-the-phase-iii-studies-of-murepavadin-for-the-treatment-of-patients-with-nosocomial-pneumonia
- [other] BioCentury, July 2019: Polyphor closes the phase III PRISM trials of intravenous murepavadin over a higher-than-expected incidence of acute kidney injury and plans to continue an inhaled form. Read October 29, 2026. https://www.biocentury.com/article/302820/july-19-clinical-quick-takes-polyphor-closes-phase-iii-murepavadin-trials-plus-takeda-and-alector
- [other] Spexis AG (formerly Polyphor), press release, January 9, 2023: first-in-human single-ascending-dose study of inhaled murepavadin in 39 healthy volunteers; well tolerated on preliminary blinded data, systemic bioavailability under 5%. Read October 29, 2026 (reproduced by the BEAM Alliance). https://beam-alliance.eu/spexis-reports-solid-safety-and-pharmacokinetics-results-from-first-in-human-study-with-inhaled-murepavadin-a-novel-macrocycle-compound
- [clinical-trial] Wach A, et al. "Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses." Antimicrob Agents Chemother, 2018;62(4). PMID: 29437621.
- [clinical-trial] Dale GE, et al. "Pharmacokinetics, Tolerability, and Safety of Murepavadin, a Novel Antipseudomonal Antibiotic, in Subjects with Mild, Moderate, or Severe Renal Function Impairment." Antimicrob Agents Chemother, 2018;62(9). PMID: 30012756.
- [review] Martin-Loeches I, et al. "Murepavadin: a new antibiotic class in the pipeline." Expert Rev Anti Infect Ther, 2018;16(4):259-268. PMID: 29451043.
- [pubmed] Sader HS, et al. "Antimicrobial Activity of Murepavadin Tested against Clinical Isolates of Pseudomonas aeruginosa from the United States, Europe, and China." Antimicrob Agents Chemother, 2018;62(7). PMID: 29686157.
- [pubmed] Sader HS, et al. "Murepavadin activity tested against contemporary (2016-17) clinical isolates of XDR Pseudomonas aeruginosa." J Antimicrob Chemother, 2018;73(9):2400-2404. PMID: 29901750.
- [pubmed] Ekkelenkamp MB, et al. "Susceptibility of Pseudomonas aeruginosa Recovered from Cystic Fibrosis Patients to Murepavadin and 13 Comparator Antibiotics." Antimicrob Agents Chemother, 2020;64(2). PMID: 31767727.
- [pubmed] Díez-Aguilar M, et al. "Murepavadin antimicrobial activity against and resistance development in cystic fibrosis Pseudomonas aeruginosa isolates." J Antimicrob Chemother, 2021;76(4):984-992. PMID: 33367642.
- [pubmed] Díez-Aguilar M, et al. "Anti-biofilm activity of murepavadin against cystic fibrosis Pseudomonas aeruginosa isolates." J Antimicrob Chemother, 2021;76(10):2578-2585. PMID: 34283223.
- [pubmed] Ghassani A, et al. "Mutations in genes lpxL1, bamA, and pmrB impair the susceptibility of cystic fibrosis strains of Pseudomonas aeruginosa to murepavadin." Antimicrob Agents Chemother, 2024;68(1):e0129823. PMID: 38092672.
- [pubmed] Romano KP, et al. "Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa." Antimicrob Agents Chemother, 2019;63(9). PMID: 31235628.
- [pubmed] Hernández-García M, et al. "Unravelling the mechanisms causing murepavadin resistance in Pseudomonas aeruginosa: lipopolysaccharide alterations and its consequences." Front Cell Infect Microbiol, 2024;14:1446626. PMID: 39711784.
- [pubmed] Melchers MJ, et al. "Pharmacokinetics and Pharmacodynamics of Murepavadin in Neutropenic Mouse Models." Antimicrob Agents Chemother, 2019;63(3). PMID: 30642931.
- [pubmed] Wei X, et al. "Murepavadin induces envelope stress response and enhances the killing efficacies of β-lactam antibiotics by impairing the outer membrane integrity of Pseudomonas aeruginosa." Microbiol Spectr, 2023;11(5):e0125723. PMID: 37668398.
- [pubmed] Wei X, et al. "Murepavadin promotes the killing efficacies of aminoglycoside antibiotics against Pseudomonas aeruginosa by enhancing membrane potential." Antimicrob Agents Chemother, 2024;68(4):e0153923. PMID: 38470195.
- [pubmed] Wei X, et al. "Murepavadin Enhances the Killing Efficacy of Ciprofloxacin against Pseudomonas aeruginosa by Inhibiting Drug Efflux." Antibiotics (Basel), 2024;13(9). PMID: 39334985.
- [pubmed] Amponnawarat A, et al. "Murepavadin, a Small Molecule Host Defense Peptide Mimetic, Activates Mast Cells via MRGPRX2 and MrgprB2." Front Immunol, 2021;12:689410. PMID: 34248979.
- [pubmed] Yılmaz U, et al. "Murepavadin is a novel peptide antibiotic that exhibits potent antibiofilm activity and enhances the efficacy of conventional antibiotics against Pseudomonas aeruginosa." Biofouling, 2026;42(7):771-781. PMID: 42459059.
- [pubmed] Li D, et al. "Current and Emerging Inhaled Antibiotics for Chronic Pulmonary Pseudomonas aeruginosa and Staphylococcus aureus Infections in Cystic Fibrosis." Antibiotics (Basel), 2023;12(3). PMID: 36978351.
- [pubmed] Andolina G, et al. "A Peptidomimetic Antibiotic Interacts with the Periplasmic Domain of LptD from Pseudomonas aeruginosa." ACS Chem Biol, 2018;13(3):666-675. PMID: 29359918.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. The phase 3 and inhaled-study facts come from the developer's own press releases (Polyphor, May 9, 2019; Spexis, January 9, 2023) and a July 2019 trade report, named where used; trial status from ClinicalTrials.gov, read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.