Which AMPs Are in Clinical Trials? A 2026 Pipeline Tracker
Peptide Antibiotics
7 FDA-Approved
Only seven antimicrobial peptides have cleared the FDA, despite thousands of candidates identified since 1987.
Hancock & Sahl, Nature Biotechnology, 2006
Hancock & Sahl, Nature Biotechnology, 2006
View as imageMichael Zasloff scraped the skin of an African clawed frog in 1987 and discovered magainins, a new class of antimicrobial peptides that killed bacteria, fungi, and protozoa without harming red blood cells.[1] That finding launched a field. Nearly four decades later, the antimicrobial peptide (AMP) pipeline remains one of the most frustrating bottlenecks in drug development. Thousands of candidates have been identified. Dozens have entered clinical trials. The vast majority have failed. This tracker covers every AMP that has reached human testing, where each stands as of 2026, and what the failures reveal about the gap between laboratory promise and clinical reality. For broader context on peptide antibiotics already in use, see our pillar article on polymyxins and colistin.
Key Takeaways
- Only 7 AMPs have received FDA approval for clinical use, and most are restricted to topical or last-resort applications
- Pexiganan, the first AMP to reach Phase III trials for diabetic foot ulcers, failed to outperform placebo in 1999 and again in a repeat trial
- Omiganan completed Phase III for severe rosacea with statistically significant lesion reduction (31% vs. 14% for vehicle) and no serious adverse events
- Brilacidin matched 7 days of daptomycin therapy with a single dose in Phase II for skin infections, with zero drug-related serious adverse events
- Murepavadin's IV Phase III trial was terminated due to nephrotoxicity, but its inhaled formulation is now in clinical development for Pseudomonas lung infections
- LL-37, the only human cathelicidin, showed 6-fold faster healing rates than placebo in a Phase II wound healing trial with 34 patients
The AMPs Already Approved: What Made It Through
The FDA has approved a small group of AMPs, and their profiles reveal a pattern. Most are cyclic peptides used topically or as last-resort systemic agents. The approved list includes gramicidin, polymyxin B, colistin (polymyxin E), bacitracin, daptomycin, oritavancin, and telavancin.[2]
Daptomycin, approved in 2003, is the most recent AMP to reach the market as a systemic antibiotic. It works by inserting into bacterial cell membranes, causing rapid depolarization and cell death. Oritavancin and telavancin are dual-mechanism agents that inhibit cell wall synthesis and disrupt bacterial membranes simultaneously, sharing structural ancestry with vancomycin.
Nisin, approved as a food preservative in 1988, sits in a different regulatory category. It is heat-stable, tolerates low pH, and kills gram-positive bacteria effectively. But it has never been approved as a pharmaceutical agent.
The common thread among approved AMPs: they are either topical agents with limited systemic exposure, or they occupy clinical niches where no alternatives exist. Colistin returned to clinical use precisely because multidrug-resistant gram-negative bacteria left physicians with no other options.[3]
Phase III: The Graveyard and the Survivors
Pexiganan (MSI-78): The First and Most Instructive Failure
Pexiganan, a 22-amino-acid synthetic analog of magainin II from frog skin, was the first AMP designed from the ground up for clinical use. Genaera (then Magainin Pharmaceuticals) developed it as a topical cream for mild diabetic foot ulcer infections.
The first Phase III trial in the late 1990s enrolled patients with infected diabetic foot ulcers. The FDA rejected the application in 1999. The clinical response rate did not differ from placebo at a statistically meaningful level.
Dipexium Pharmaceuticals tried again with a second Phase III trial (NCT01594762) enrolling 220 patients. Results were nearly identical: 57.7% clinical response in the pexiganan group versus 52.4% in placebo. Microbiological eradication was actually lower in the pexiganan group (28.6%) than placebo (36.0%). The drug's topical bioavailability was simply too low to achieve therapeutic concentrations in infected tissue.
Pexiganan remains active in vitro against a broad spectrum of diabetic foot ulcer pathogens, including MRSA strains. The problem was never potency. It was delivery. This distinction matters for every AMP candidate that follows.
Omiganan (CLS001): The Quiet Success Story
Omiganan is a 12-amino-acid synthetic analog of indolicidin, a cathelicidin-family peptide. Cutanea Life Sciences developed it as a topical gel for papulopustular rosacea rather than as an antibiotic, leveraging its anti-inflammatory properties alongside its antimicrobial activity.[4]
Phase II results showed a dose-dependent response: patients receiving once-daily omiganan 2.5% had a 31% reduction in inflammatory lesions compared to 14% for vehicle. The Phase III trial for severe papulopustular rosacea (completed 2018) confirmed efficacy. Topical 1.6% omiganan gel outperformed vehicle in reducing inflammatory lesion counts and improving Investigator Global Assessment scores at week 12. No serious adverse events were reported.
Omiganan's path illustrates a recurring lesson: AMPs may succeed not as direct replacements for conventional antibiotics, but in niches where their immunomodulatory and anti-inflammatory properties provide additional value. For more on the relationship between AMPs and drug-resistant bacteria, see our article on AMPs against MRSA.
Surotomycin (CB-315): When "As Good As" Isn't Good Enough
Surotomycin, a cyclic lipopeptide developed by Cubist Pharmaceuticals (later acquired by Merck), targeted Clostridioides difficile infection. It was designed to be a narrow-spectrum agent that killed C. difficile while sparing normal gut flora, potentially reducing recurrence rates.
Two Phase III trials (PRISM-UDR and PRISM-MDR) enrolled a combined 1,120 patients. The first trial showed clinical cure rates of 79.0% for surotomycin versus 83.6% for vancomycin, failing to meet noninferiority criteria. The second trial achieved noninferiority at end of treatment (83.4% vs. 82.1%) but failed the key secondary endpoint of sustained clinical response. Development was discontinued. The bar for C. difficile treatment had already been raised by fidaxomicin, and a "noninferior" agent with no clear advantage offered no commercial path.
Murepavadin (POL7080): Pivoting from IV to Inhaled
Murepavadin targets the outer membrane protein LptD of Pseudomonas aeruginosa, making it one of the most specific AMPs ever developed. It is active exclusively against Pseudomonas species and has demonstrated potent in vitro killing of multidrug-resistant strains.
Polyphor launched two Phase III trials (PRISM-UDR and PRISM-MDR) for IV murepavadin in Pseudomonas pneumonia. Both were terminated after reports of acute kidney injury in treated patients. The nephrotoxicity was a systemic delivery problem, not an inherent flaw in the peptide's mechanism.
The development strategy pivoted to inhaled delivery. Inhaled murepavadin delivers the peptide directly to the lung epithelium, bypassing systemic circulation entirely. Early clinical data from the inhaled formulation showed improved clinical symptoms and reduced bacterial burden compared to controls. As of 2026, inhaled murepavadin remains in active clinical development, representing one of the most promising gram-negative-specific AMPs in the pipeline.
Phase II: Candidates Still in Play
Brilacidin (PMX-30063): A Defensin Mimic With Two Shots on Goal
Brilacidin is not a peptide in the traditional sense. It is a synthetic small molecule designed to mimic the structure and function of human defensins, the innate immune peptides that form the first line of antimicrobial defense in your body.[5]
In a Phase IIb trial for acute bacterial skin and skin structure infections (ABSSSI), a single dose of brilacidin matched seven days of daptomycin therapy. Of 215 randomized subjects, the efficacy comparison was favorable with zero drug-related serious adverse events. Innovation Pharmaceuticals also tested brilacidin as an oral rinse for preventing severe oral mucositis in head and neck cancer patients receiving chemoradiation. In the Phase II trial, severe oral mucositis incidence dropped to 25.0% in the treatment group versus 71.4% in placebo patients receiving aggressive chemotherapy regimens. The FDA cleared brilacidin for Phase III in oral mucositis prevention in 2018. As of 2026, the company continues development across multiple indications.
LL-37: Testing Your Own Immune Peptide as a Drug
LL-37, the only cathelicidin produced by the human body, is a 37-amino-acid peptide with broad-spectrum antimicrobial activity and immunomodulatory properties.[6] It kills bacteria by disrupting their membranes, but it also recruits immune cells, promotes wound healing, and modulates inflammation. For a deeper look at this peptide's biology, see our article on LL-37: The Only Human Cathelicidin.
The first-in-human trial tested topical LL-37 for hard-to-heal venous leg ulcers. In the Phase I/II study with 34 participants, the 0.5 mg/mL dose produced healing rate constants approximately six-fold higher than placebo (p = 0.003). The two lower doses decreased mean ulcer area by 68% and 50%, respectively. Higher doses (3.2 mg/mL) showed no benefit over placebo, suggesting a bell-shaped dose-response curve. No safety concerns emerged.[7]
A separate Phase I/II trial evaluated intratumoral LL-37 injections for melanoma, completed in 2024. The trial demonstrated safety and tolerability, with evidence of tumor microenvironment modulation that may enhance anti-tumor immune responses.[8]
DPK-060: Targeting Infected Eczema
DPK-060, derived from the human protein kininogen, completed a Phase II trial for acute external otitis and infected atopic dermatitis. It is a 24-amino-acid peptide engineered for improved stability and reduced toxicity compared to native sequences. Published trial data showed comparable efficacy to standard treatment, with good tolerability. Development continues but has not advanced to Phase III as of early 2026.
Phase I and Preclinical: The Next Wave
Arenicin-3 Analogs
Arenicin, originally isolated from the marine lugworm Arenicola marina, is an 18-residue beta-hairpin peptide with potent activity against gram-negative bacteria, including colistin-resistant strains. Synthetic analogs with improved selectivity indices have entered early-stage clinical evaluation. The peptide's compact structure and salt tolerance make it an attractive template for gram-negative-targeted development.
AI-Designed AMPs
Machine learning models trained on the Antimicrobial Peptide Database (which catalogs over 3,000 natural AMPs) are generating novel sequences optimized for potency, selectivity, and stability simultaneously.[9] In 2025-2026, several AI-designed AMPs entered preclinical testing. The approach allows rapid iteration: computational tools predict antimicrobial activity, hemolytic toxicity, and protease stability before any peptide is synthesized. For more on this approach, see Machine Learning for Antimicrobial Peptide Prediction.
Exebacase (CF-301): A Lysin That Almost Worked
Exebacase is not technically an AMP but a bacteriophage-derived endolysin that attacks the peptidoglycan cell wall of Staphylococcus aureus. In Phase II, a single dose added to standard antibiotics produced 42.8% higher clinical responder rates than standard-of-care alone for S. aureus bloodstream infections. The Phase III DISRUPT trial (NCT04160468) was launched in 2019 but terminated in 2022 after failing to meet its primary endpoint. The concept of using lytic enzymes alongside traditional antibiotics remains active in other programs.
Why AMPs Keep Failing: The Five Barriers
The pattern across failed AMP trials is consistent. Five barriers account for the majority of clinical failures.
Protease degradation. Linear peptides are rapidly broken down by blood and tissue proteases. Pexiganan's topical bioavailability problem stems directly from enzymatic degradation in wound fluid. Strategies to address this include D-amino acid substitution, cyclization, and peptidomimetic design.[10]
Systemic toxicity. AMPs that disrupt bacterial membranes can also damage host cell membranes at higher concentrations. Murepavadin's nephrotoxicity is the starkest example. The therapeutic window between bacterial killing and host cell damage remains narrow for many candidates.
Serum binding. Many cationic AMPs bind to serum proteins and lose activity in blood. A peptide that shows impressive minimum inhibitory concentrations (MICs) in laboratory media may be functionally inactive in vivo. This serum-binding effect explains why many AMPs that look promising in vitro fail in animal models.
Manufacturing cost. Peptide synthesis remains expensive compared to small molecule production. Solid-phase peptide synthesis costs for clinical-grade AMPs range from $100 to $600 per gram at manufacturing scale. This limits commercial viability, especially for topical products that require large quantities.
Regulatory mismatch. The FDA approval pathway was built for conventional antibiotics. AMPs often have novel mechanisms (membrane disruption, immunomodulation) that do not fit neatly into existing efficacy endpoints. Several AMP trials have struggled with endpoint selection, measuring the wrong thing at the wrong time.
What the Survivors Have in Common
The AMPs still advancing through clinical development share a few features. They target specific niches rather than competing head-to-head with broad-spectrum antibiotics. They exploit delivery routes (topical, inhaled, intratumoral) that avoid systemic exposure. They leverage immunomodulatory properties alongside direct killing. And they address conditions where conventional antibiotics are failing, particularly multidrug-resistant infections where the competitive bar is lowest because alternatives barely exist.[11]
The AMR crisis creates a paradox for AMP development: the clinical need is enormous, but the economic incentives remain misaligned. Antibiotics generate less revenue than chronic disease drugs, and AMPs are more expensive to manufacture than small molecules. The AMPs' role in agricultural settings and the growing understanding of natural AMP diversity may eventually provide alternative commercial pathways.
The Bottom Line
The antimicrobial peptide pipeline has produced thousands of candidates over four decades, but only a handful have reached or passed Phase III. The pattern is clear: AMPs fail when forced into the conventional antibiotic mold (systemic delivery, broad-spectrum targets, head-to-head noninferiority trials). They succeed when matched to specific delivery routes, niche indications, and conditions where their immunomodulatory properties matter as much as their killing power. As of 2026, the most promising programs, including inhaled murepavadin, brilacidin, and LL-37, all follow this pattern.