SNIPR phage therapy clears MDR infection in first patient
A kidney transplant patient with a rare, multidrug-resistant (MDR) infection has become the first to be treated using an adjunctive bacteriophage therapy developed by Denmark's SNIPR Biome.
The SNIPR001 therapy takes the form of a bacteriophage – a virus that only infects bacteria – that is modified using CRISPR gene-editing techniques to selectively target Escherichia coli, a major cause of MDR infections.
It was used to treat a serious case of MDR E coli malakoplakia, a rare chronic inflammatory condition that results in persistent infection within macrophage cells, which are unable to digest the bacteria properly, and the formation of granulomatous masses in the body.
The patient, a 65-year-old man, had a kidney transplant in 2023 after developing the rare disorder focal sclerosing glomerulosclerosis (FSG), but subsequently developed recurrent, complicated infections with E coli, made harder to manage by his need to take immune-suppressing medications to avoid transplant rejection.
Multiple prolonged courses of antibiotics failed to defeat the infection, which eventually became resistant even to last-line carbapenem antibiotics, and he went on to develop malakoplakia and the formation of a large mass originating from the wall of his bladder and prostate.
Faced with no more treatment options, his clinical team – based at the University of California San Diego – sought and secured approval for compassionate use of SNIPR001, which was administered intravenously, topically, and injected into the lesion, in combination with antibiotics, to try to get the malakoplakia under control.
The result? Rapid healing of abdominal lesions and sustained radiographic regression of disease burden, with the size of the mass shrinking by nearly 90% from 745 cm3 at the start of treatment to 82 cm3 after a year. Urine and tissue samples revealed no evidence of the infection, and there was no evidence of any harmful side effects of the bacteriophage therapy.
"For a patient facing a rare infection with very limited therapeutic options, phage therapy offered a novel approach that was both well tolerated and associated with a remarkable clinical response," said Saima Aslam, professor of medicine in the division of infectious diseases and global public health at UCSD and corresponding author on the report on the case study, published in the journal Clinical Infectious Diseases.
Bacteriophages have long been proposed as a possible answer to the rising levels of antimicrobial resistance among bacterial pathogens and, while none have yet been approved for routine clinical use, there have been various case reports of compassionate use and small-scale clinical trials in specific conditions, such as chronic infections with Pseudomonas aeruginosa in cystic fibrosis patients.
SNIPR001 – SNIPR Biome's lead drug candidate – now joins that select group, and the case study follows a phase 1a first-in-human trial of the bacteriophage therapy in healthy subjects, which showed it could be safely administered and had no effect on the normal bacterial population of the gastrointestinal tract.
It has now completed recruitment of patients for a phase 1b/2a trial of an oral formulation of SNIPR001 in people with blood cancer to see if it can prevent E coli infections in the blood, and is also developing the therapy for active E coli infections.
"This case report marks an important clinical milestone for SNIPR001 and highlights the potential of our engineered CRISPR medicine platform to address difficult-to-treat, drug-resistant E coli infections," said the company's chief executive, Dr Christian Grøndahl.
