Contents of this article
Press release written by Jason Clark, Director and Chief Scientific Officer at NexaBiome.
The search for alternative treatments to antibiotics is intensifying as antimicrobial-resistant infections continue to rise worldwide. It’s clear to see why the World Health Organization (WHO) has ranked antimicrobial resistance (AMR) as one of the most pressing global health threats, affecting not just human and animal health but also food security. At the forefront of promising treatments is phage therapy.
Bacteriophages – or phages – have existed for more than a billion years and were used successfully in Eastern European medicine for decades, but they have been underutilised in mainstream Western medicine since the onset of the antibiotic era. With antibiotic resistance worsening, and superbugs on the rise, this is changing.
A global challenge
AMR is estimated to have been directly responsible for 1.27 million deaths globally in 2019 and if left unchecked, it’s predicted that by 2050, drug-resistant bacterial diseases could claim up to 10 million lives each year. The issue occurs when bacteria, viruses, fungi or parasites develop resistance to antimicrobial medicines, often due to antibiotic overuse and misuse, rendering an increasing number of standard treatments ineffective. This problem is being compounded by the slowing pace of new antibiotic development.
In response to this escalating health threat, there’s been a shift in focus towards alternative therapies – both at a national and global level – with phage therapy increasingly seen as a critical alternative or complementary treatment to antibiotics for bacterial infections.
Phages are viruses that specifically target and kill bacteria by infecting and replicating within them. In fact, every two days half the bacteria on the planet are killed by phages. Unlike antibiotics, which indiscriminately kill both harmful and beneficial bacteria, phages are very specific to their targets, minimising collateral damage to the body’s microbiome, leaving the healthy microbiome intact. Currently, phages are predominantly used as a last-resort treatment in human medicine and despite their effectiveness, certain challenges have hindered widespread adoption. Here, we address three misconceptions about phage therapy.
The regulatory pathway
A lack of clear regulatory guidance has been seen as a barrier to the development and approval of phage therapy for widespread use. However, the reality is more nuanced – this support has always existed, it just hasn’t been compiled in one place. But now with new guidance issued by the Medicines and Healthcare products Regulatory Agency (MHRA), the regulatory framework and for phage therapy products is clearer than ever.
This landmark move marks a significant step forward, providing a structured regulatory path for the development and deployment of phage therapy in the UK. The MHRA’s guidance is the first of its kind and comes in tandem with the establishment of a national phage service by the UK Health Security Agency (UKHSA), further underscoring the UK’s commitment to integrating phage therapy into mainstream healthcare. With a defined framework in place, the path to clinical adoption is clearer than ever before.
Additionally, initiatives such as the Phage Innovation Network and successful cases of compassionate use phage therapy have demonstrated the potential phages hold in treating drug-resistant infections and combatting AMR. The increasing regulatory clarity also signals a shift in the perception of and growing appetite for phage therapy.
Scalable treatments
Now to the question of whether phage therapy is too complex and time-consuming to scale, given its personalised nature (each bacterial strain requires its own unique phage). Advances in biotechnology and AI mean optimal phage combinations can be identified more quickly, accelerating the formulation process and paving the way for the development of so-called phage cocktails (combinations of different phages that enhance efficacy in personalised medicine).
For approval in the UK, phages must adhere to GMP (Good Manufacturing Practice) standards to guarantee quality, safety and efficacy. A lack of GMP-compliant facilities, and the issue of phage specificity, have been seen as potential barriers to large-scale production.
AI-driven approaches also enhance bacteriophage manufacturing and production, which means scaling treatments has never been easier. Traditional phage preparation methods are being replaced with optimised, continuous production systems that can efficiently scale up to meet demand. Mathematical modelling and AI-assisted genome modification further refine phage development, allowing for precision-engineered phages tailored to combat resistant bacterial strains.
As these innovations continue to drive progress, calls are mounting for further investment in necessary infrastructure, reflecting the growing recognition of phage therapy as a viable alternative treatment, and a key tool in the fight against AMR. This will hopefully pave the way for GMP-compliant facilities and a dedicated phage bank, ensuring long-term integration of phage therapy into mainstream healthcare.
Efficacy
Phage therapy is increasingly recognised as highly effective for treating bacteria-resistant infections that do not respond to conventional treatments. Any questions about phage effectiveness can be easily dispelled by the mounting body of evidence demonstrating its success. A particularly promising application is in the treatment of diabetic foot infections (DFIs), a serious complication affecting up to one-third of diabetic patients worldwide, where phage therapy is showing transformative potential. DFIs often result in chronic wounds and, in severe cases, amputation or death. The rise of AMR has made treating these infections increasingly difficult, underscoring the urgent need for alternative therapies.
In compassionate use cases, phages have been shown to effectively target antibiotic-resistant bacteria and biofilms that form in chronic wounds, significantly improving patient outcomes. In one study conducted in Scotland, phage therapy prevented amputation in six out of 10 patients, showed clear improvement in two and only failed in one. These results are particularly significant given that the patients had the most difficult to treat, severe, infections that had failed to respond to all other treatments, and where the only alternative was amputation.
To build on this success, we are pioneering the use of phage therapy for DFIs through our patented phage stabilisation technology, to develop room temperature stable phage-based wound dressings. This will enable a far broader application in both hospitals and outpatient care and at an earlier stage in the patient’s care, helping to treat and prevent serious complications of these infections.
In addition to its clinical success, phage therapy is proving to be a cost-effective and viable solution that can reduce the burden on healthcare systems while improving patient outcomes. A healthcare cost analysis conducted by Health Improvement Scotland found that combining phage therapy with standard care was both more cost-effective and successful than standard care alone, especially considering the cost of health care for diabetic-related ulceration and amputation has been estimated at almost £1 billion per year.
A paradigm shift in medicine
Phage therapy is not a futuristic concept; it is a well-established treatment with a proven and growing track record. With the recent MHRA guidelines clarifying regulatory pathways, AI-driven advancements streamlining phage production, and compelling clinical evidence of its effectiveness, phage therapy is on the verge of broader mainstream adoption.
As AMR continues to threaten global health, it is clear that embracing phage therapy is not just an option, but a necessity. Momentum is growing, and with continued investment, research, and regulatory support, it is only a matter of time before phage therapy becomes a cornerstone in the fight against drug-resistant infections.
