Recent News 59 : Phage Therapy in 2025: From Century-Old Cure to Modern Clinical Challenge

Phage Therapy in 2025: From Century-Old Cure to Modern Clinical Challenge

Phage therapy - the therapeutic use of bacteriophages to treat bacterial infections—has re‑entered the clinical mainstream. Despite a century of use, there is still no centrally approved product in the US or EU. This article reviews the current state of the field in 2025, linking current clinical programs, our curated clinical-trials dataset, and historical practices in Georgia and Poland, and then identifies the infrastructure still needed for broad adoption.

Industry Push Toward Clinically Validated Phage Therapy: BiomX and the Road Ahead

BiomX (NYSE: PHGE) has entered a pivotal stage with its therapeutic phage programs, by initiating a randomised, double-blind, placebo-controlled Phase 2b trial of BX004 for chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF)(1). The first patient was dosed in July 2025, marking a significant milestone after the earlier Phase 1b/2a study and the publication of peer-reviewed results for BX004-A (2).

In parallel, BiomX has reported positive Phase 2 results for BX211 in diabetic foot osteomyelitis (DFO), with more than 40% mean ulcer area reduction by week 10 (3). The company has indicated its intent to move the program forward into later stages.

These programs highlight a crucial reality: the future of phage therapy is not just on microbiological proof, but on building the ecosystem around it. Scalable manufacturing, well-designed trials, relevant clinical endpoints, and clear regulatory routes will determine whether phages remain a niche solution or become a mainstream therapy.

BiomX is not alone in this effort. Several companies from your curated clinical trial list are actively pursuing human therapeutic phages, e.g.:

• Armata Pharmaceuticals, Inc. Pharmaceuticals (USA) – Developing AP-PA02 for P. aeruginosa in CF and AP-SA02 for S. aureus bacteremia.
• Pherecydes Pharma (France) – Focused on S. aureus bone and joint infections, often in partnership with academic hospitals.
• INTRALYTIX, INC. (USA) – Programs targeting Clostridioides difficile, Salmonella, and other enteric pathogens.
• TechnoPhage, SA (Portugal) – TP-102 for diabetic foot infections and bone-associated S. aureus.
• NexaBiome (UK) – Preclinical and early-clinical work on phage stabilisation and delivery systems.

Parallel to industry, academic teams worldwide—including the Eliava Institute (Georgia), the Phage Therapy Unit in Wrocław (Poland), and research groups in other parts of the world—continue to investigate phages as alternatives or adjuncts to antibiotics. Academia contributes to a valuable understanding of how phages work and advances their use in compassionate-treatment cases; however, the gap between bench and an approved, scalable therapeutic product remains striking.

A Century-Old Story

Bacteriophages were first described independently by Frederick Twort in 1915 and Félix d’Hérelle in 1917, who rapidly recognised their potential as therapeutic agents (4,5).

By the early 1920s, clinical use of phages aginst bacterial infections was underway, predating antibiotics as antibacterial tools in several regions.

Tbilisi: "the phage kingdom"

In the Soviet Union, Tbilisi, Georgia, became the epicentre of phage therapy. In 1923, Giorgi (George) Eliava, working with d’Hérelle, founded what would later be named the George Eliava Institute of Bacteriophage, Microbiology, and Virology (6). During the Soviet era, the institute maintained large-scale phage manufacturing, curated extensive phage banks, and supplied hospitals, pharmacies, and the Red Army (6,7). It continued operations after the dissolution of the USSR, still producing personalised and cocktail phage formulations for patients today(8).

With the success in the East, why were phages forgotten in Western medicine. Several factors can explain it:

• The introduction and mass production of antibiotics in the 1940s, which were easier to produce, store, and standardise (7).
• Variable trial quality in early phage studies and limited understanding of phage biology (9).
• Soviet-era research was largely published in Russian or Georgian and was inaccessible to most Western scientists (10).
• Cold War politics discouraged technology transfer between the USSR and the West(11).

Following the Cold War, Georgia, Russia, and Poland remained pillars of continuity, maintaining phage therapy programs when most countries had abandoned them (12).

Poland: The Wrocław Model

In 2005, shortly after joining the EU, the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław established the Phage Therapy Unit (PTU)—Europe’s first ethics-approved phage therapy program. The PTU operates under Article 37 of the Declaration of Helsinki (“Unproven Interventions in Clinical Practice”) and the Polish Act on the Medical Profession (13).

Its protocols require:

• Classification of all treatments as experimental, with case-by-case ethical review.
• Informed consent from patients.
• Systematic reporting of outcomes in peer-reviewed journals (14,15).

The PTU represents a bridge between Soviet-era operational knowledge and modern EU ethical frameworks.

Key milestones in Phage Therapy developement.

From Legacy to Opportunity

Historical centres such as Tbilisi’s Eliava Institute and Wrocław’s PTU show that phage therapy can be operationalised and sustained for decades, even outside of formal drug approval systems. Their archives document thousands of patient cases, and their laboratories have decades of experience in large-scale production, cocktail adaptation, and phage banking (6,9,14).

The challenge now is to harmonise these long-standing practices with EMA, FDA, and WHO guidance—turning this century of operational know-how into globally approved, reimbursable, and scalable therapies (16).

Clinical Reality in 2025: From Legacy to Pipeline

The century-old divide between East and West in phage therapy is narrowing—but not yet closed. What was once the domain of Soviet-era institutes and a few pioneering EU centres is now a small but growing clinical pipeline, visible in global trial registries.

To understand the current landscape, we conducted a targeted review of registered human phage therapy studies. Using ClinicalTrials.gov (search on 05AUG2025)as the primary source, all clinical trials containing the term "phage" were selected. For further analyses, strict inclusion criteria were applied:

• Included: Interventional trials and documented compassionate-use cases where therapeutic phages were administered to humans.
• Excluded: Phage display technology, purely diagnostic applications, and preclinical or observational work without human dosing.

A total of 66 therapeutic studies (out of 119) were qualified for further review—a real-time snapshot of where clinical phage research stands in 2025.

What we found:

• Trial status: 17 completed, 28 active, 11 terminated, and 10 with unknown status.
• Phase distribution: Strong skew toward early development—Phase 1/2 (n = 19), Phase 1 (n = 7), Phase 2 (n = 8), only three Phase 3 trials worldwide, plus one Phase 2/3 trial, one early Phase 1, and 27 with no reported phase.
• Geography: The United States leads (n = 37), followed by France (n = 9) and Canada/Israel (n = 5 each), with smaller clusters in several other countries.
• Indications: Chronic lung infections in cystic fibrosis, prosthetic joint and bone infections, diabetic complications, urinary tract infections, gastrointestinal disorders, and wound/skin infections dominate the field.
• Pathogens: Pseudomonas aeruginosa (n = 7) and Staphylococcus aureus (n = 5) are the most frequently targeted, with most trials not specifying a single pathogen.
• Sponsorship: Academia and hospitals dominate (n = 37), followed by industry (n = 26), with government-only sponsorship rare (n = 3).

Summary of Clinical Trial today.

Even with this post-2020 momentum, there remains a striking absence of EMA or FDA-approved phage therapeutics(11,16,17). Patient access still relies on three main channels:

• Participation in clinical trials.
• Belgium’s magistral framework, allowing pharmacy-prepared individualized phages.
• Compassionate-use or emergency protocols (e.g., FDA eIND).

What this means:

Phage therapy is transitioning from historical anecdote to structured clinical evaluation—but progress remains patchy. The trial map shows enthusiasm and diversity of indications, yet the low number of late-phase studies suggests that most candidates have not crossed the translational “valley of death” (18). In other words, the clinical reality is one of potential without yet achieving permanence. If the first century of phage therapy was about proving they can work, the next decade must prove they can be standardised, regulated, and reimbursed (16,17). Until then, the gap between what is possible and what is available will persist.

What “Infrastructure” Means in 2025 – and Why It’s Still Missing

If the first century of phage therapy was defined by biological proof of concept, the second century will be defined by infrastructure. In 2025, no matter how elegant the virology, no phage program can reach patients at scale without the regulatory, manufacturing, and clinical systems to support it.

a) Regulatory & Manufacturing Foundations

For the first time, the European Medicines Agency (EMA) has signalled readiness to define a harmonised framework for bacteriophage therapeutics. Its 2023 Concept Paper outlines requirements for quality, safety, and efficacy assessment, with strong emphasis on CMC (Chemistry, Manufacturing, and Controls), quality control (QC), stability studies, and—critically—comparability plans for updating multi-phage cocktails over time (7).

Belgium’s magistral route remains the most mature real-world example. In this model, patient-specific phage formulations are prepared in authorised hospitals or community pharmacies under national oversight. Recent peer-reviewed case series have documented clinical outcomes using magistral phages  (11,12), while quality monographs from the Belgian Federal Agency for Medicines and Health Products (FAMHP) provide standardised production criteria(17).

Yet, even this system is limited in scale. Without cross-border recognition, each country must reinvent its pathway—slowing adoption.

b) The “Clinical Operating System”

Even with a viable regulatory framework in place, most clinical microbiology labs still lack a functional operating system for phage therapy—one capable of delivering rapid, validated phagogram testing under clinically urgent timelines (19).

Endpoints also remain inconsistent across indications, making it difficult to compare outcomes or establish broadly accepted success criteria (20,21):

• Cystic fibrosis (CF): Trials often measure either lung function improvement (e.g., FEV₁) or Pseudomonas aeruginosa clearance, but rarely integrate both into a composite primary endpoint, limiting comparability and clinical relevance.
• Diabetic foot osteomyelitis (DFO): Outcome measures vary between ulcer healing, infection resolution, and limb salvage, with no consensus on which best reflects therapeutic success.

Moreover, foundational PK/PD and immunogenicity data are still sparse, forcing empirical rather than evidence-based dosing and duration decisions—one of the most significant regulatory and payer obstacles (22).

c) Evidence Exemplars – Proof It Can Be Done

Two milestones in the past decade have shaped modern confidence in phage therapy e.g.:

• The engineered phage rescue in disseminated Mycobacterium abscessus — a single-patient compassionate use case demonstrating how synthetic biology can rescue otherwise untreatable infections (23).
• The BX004 program by BiomX — progressing from controlled early-phase data (2) and a Phase 2b trial in CF patients with chronic Pseudomonas aeruginosa infection (NCT06998043).

These cases prove that phages can meet modern scientific standards—when the infrastructure exists.

What It’s Still Missing

Despite a century of anecdotal success and scattered clinical victories, phage therapy is still not a routine licensed treatment. The bottleneck is no longer the basic science—it’s the ecosystem:

• No harmonised global regulatory framework (7,17).
• Limited GMP-ready manufacturing capacity (8,10).
• Inconsistent clinical endpoints and diagnostic readiness (16).
• Gaps in PK/PD and immune response data (24).

As Jonathan Solomon , CEO of BiomX, reflects:

“We’re not just developing drugs—we’re developing the infrastructure for a new era of infection control.” (25)

The challenge is clear: without that infrastructure, even the best phage candidates will remain trapped in early trials, while patients continue to rely on compassionate use as a last resort.

Where to Build

Even in 2025, the gap between compelling case reports and globally marketed phage products remains wide. Priority build-points include:

Infrastructure priorities:

• Validated phagogram standards with prospective correlation to patient outcomes, moving beyond multiplicity of infection (MOI) or end-of-plaque (EOP) readouts (18).
• CMC comparability rules for adaptive phage cocktails, with clear regulatory triggers for when phage replacement or formulation changes require a new filing (16).
• Reimbursement archetypes for personalised or rapidly iterated biologics, recognising that magistral frameworks provide access but not formal market authorisation  (11).

Scientific data gaps:

Beyond regulatory and manufacturing readiness, several core scientific uncertainties continue to limit phage therapy’s translational momentum.

• In vivo resistance development — how bacterial populations adapt under therapeutic phage pressure (24,26)
• Host immune interactions — including anti-phage antibody kinetics that may shorten therapeutic windows (27).
• Pharmacokinetics/pharmacodynamics (PK/PD) evidence for optimal dose, route, and duration, still minimal for most clinical candidates(28),
• Scalable delivery systems capable of reliably reaching deep-seated infections such as osteomyelitis, endocarditis, or device-associated biofilms (29,30).

These gaps—especially when combined with the need for precision delivery to infection sites—highlight why standardised, multicentre, late-phase trials remain essential.

Conclusion – Science Isn’t the Problem

Phage therapy works.

Is it hard? Yes.

Do we have clear regulations? No.

The barrier isn’t the science—it’s policy. Until frameworks catch up, patients will keep waiting for a treatment we already know can save lives!

We need to demand:

• Standardised diagnostics integrated into routine microbiology.
• GMP phage supply chains capable of rapid yet compliant adaptation.
• Comparator-ready clinical trials that meet contemporary evidentiary standards.

Clear, harmonised regulatory pathways to sustain innovation without sacrificing quality.

If the last century gave us science, this one can deliver the systems. With aligned infrastructure, phage therapy can evolve from niche rescue to mainstream precision anti-infective.

Disclaimer:

This article is a brief analytical overview based on publicly accessible sources, prepared independently by MicroBioBridge Consulting. The Phage Therapy is only republishing it and is not responsible for any of the following statements. It does not represent a complete or exhaustive review of phage therapy research, clinical programs, or regulatory frameworks. All interpretations are for informational purposes only and do not constitute medical, scientific, or investment advice.

References

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