BX004 phage therapy improves CF lung function: Top-line trial data
Inhaled therapy led to significant reductions in P. aeruginosa load after 10 days
BX004, an inhaled phage therapy being developed for chronic Pseudomonas aeruginosa lung infections, led to clinically meaningful improvements in lung function for cystic fibrosis (CF) patients with existing lung impairments, according to top-line results from the Phase 2 part of an ongoing Phase 1b/2a clinical trial.
The therapy also led to significant reductions in P. aeruginosa bacterial load after 10 days of treatment.
BX004’s developer, BiomX, now plans to advance the treatment to a pivotal Phase 2b/3 trial, pending regulatory feedback and funding. A pivotal trial is one where, should the findings be positive, they may support an application for marketing approval.
“This is truly a watershed moment, not only in the clinical development of phage therapy, but also for the entire CF community,” Robert T. “Chip” Schooley, MD, professor and co-director of the Center for Innovative Phage Applications and Therapeutics at the University of California, San Diego, said in a company press release.
“These results take us one step closer toward bringing forward a new and effective phage-based treatment option that CF patients desperately need to address these deadly pulmonary infections, and I look forward to its continued clinical advancement,” he added.
Chronic, serious lung infections often caused by P. aeruginosa
In CF, the buildup of thick, sticky mucus in the lungs provides a breeding ground for bacteria. Chronic and serious lung infections, often caused by P. aeruginosa, are common and contribute to lung function declines.
While antibiotics are the first-line treatment, bacteria can develop a resistance to them when they are used too often or for too long. This limits antibiotic effectiveness and makes the infections especially difficult to treat.
Bacteriophages, or simply phages, are a type of virus that naturally invade and kill off only bacterial cells, but don’t infect human cells. They show promise for fighting off antibiotic-resistant infections in CF.
BX004 is a cocktail of phages intended to specifically target P. aeruginosa when inhaled directly into the lungs. It holds fast track designation in the U.S., which is intended to help accelerate the therapy’s development.
The Phase 1b/2a study (NCT05010577) is evaluating the therapy’s safety and effectiveness among adults with CF and chronic P. aeruginosa infections who are also receiving standard-of-care antibiotics.
In the first part, nine participants received an ascending dose of BX004 (seven people) or a placebo (two people) for one week. Results indicated those who received the therapy showed greater reductions in P. aeruginosa than those on placebo.
This is truly a remarkable result when one considers the fact that all three patients had P. aeruginosa lung infections for at least 13 years, with one patient having a Pseudomonas aeruginosa infection for 35 years.
Phase 2 testing effects of longer treatment period in CF patients
The Phase 2 portion, which finished dosing last month, was designed to test the effects of a longer treatment period in a larger number of patients. A total of 34 CF patients were randomly assigned to receive inhaled BX004 (23 people) or a placebo (11 people) twice daily for 10 days.
Among a predefined subgroup of participants who had impaired lung function at the study’s start, BX004 led to a clinically meaningful, 5.67% improvement in lung function relative to a placebo, as assessed by the forced expiratory volume in 1 second (FEV1) test.
Specifically, these patients experienced a 1.46% improvement in FEV1 performance, whereas those on placebo worsened by 4.21%.
Likewise, BX004 was associated with an 8.87-point relative increase, or improvement, in scores on the respiratory domain of the Cystic Fibrosis Questionnaire-Revised, a measure of life quality related to lung function, compared to the placebo.
“We believe that this data is extremely promising noting the short treatment duration of 10 days,” Jonathan Solomon, BiomX’s CEO, said in a written Q&A with Cystic Fibrosis News Today. “[These] signals demonstrate that phage treatment with BX004 could improve lung function and quality of life for patient suffering from chronic P. aeruginosa infections.”
In the BX004 arm, three of 21 people (14.3%) tested negative for P. aeruginosa in secretions from the respiratory tract (sputum) at the end of treatment, whereas this was not achieved by any patient in the placebo arm.
“This is truly a remarkable result when one considers the fact that all three patients had P. aeruginosa lung infections for at least 13 years, with one patient having a Pseudomonas aeruginosa infection for 35 years,” Solomon said.
“In fact, this same patient remained culture negative approximately 2 months after end of treatment,” he added.
While P. aeruginosa levels in the sputum were variable across the entire study group, researchers believe this could be attributed to differences in the type of antibiotic treatment regimen being used. Some patients remained consistently on one type of antibiotic (continuous regimen), whereas others alternated treatments or cycled on and off the antibiotics.
BX004 led to reduced P. aeruginosa burden in patients on continuous antibiotic
Looking at just the subgroup of patients on a continuous regimen, BX004 led to a significant reduction in P. aeruginosa burden by the end of treatment, compared to a placebo, which was greater than those observed in the trial’s first part.
While that could be related to the longer treatment period, Solomon also noted patients in part 1 did not receive the full dose of BX004 for all seven days of treatment.
“The full dose twice daily was only given for the last 4 days … In the Part 2 we administered 10 days of the full dose,” Solomon said.
BX004 was found to be safe and well tolerated, with no serious adverse events or acute lung symptom exacerbations related to the treatment. No evidence of resistance to the phage therapy was observed.
While promising, the findings from this small study will need to be confirmed in the planned Phase 2b/3 trial, Solomon said.
“We believe that the favorable safety profile, lack of evidence of treatment related phage resistance and clinical benefits observed support a longer treatment duration,” he said. “We anticipate a longer treatment duration … of potentially several weeks or months could [result] in a more pronounced and sustainable effect.”