In a significant advancement for bacteriophage therapeutics, Armata Pharmaceuticals has announced positive topline results from its Phase 1b/2a diSArm clinical trial evaluating AP-SA02, a novel intravenous multi-phage therapeutic for the treatment of complicated Staphylococcus aureus bacteremia.
The randomized, double-blind, placebo-controlled study demonstrated that AP-SA02, when administered alongside best available antibiotic therapy (BAT), significantly improved clinical outcomes compared to BAT alone, meeting all primary endpoints for safety, tolerability, and clinical response in the intent-to-treat population.
"This trial and these data are what the field of phage therapy has been eagerly awaiting for over a decade and represent a critical leap forward for Armata and for the role of bacteriophages in combating life-threatening systemic infections," stated Dr. Deborah Birx, Chief Executive Officer of Armata.
Trial Design and Safety Profile
The diSArm study enrolled 50 subjects who received at least one dose of AP-SA02 or placebo. The bacteriophage therapy was administered intravenously every six hours for five days in addition to best available antibiotic therapy.
AP-SA02 demonstrated a favorable safety profile with no serious adverse events related to the study drug. Only two subjects experienced adverse events possibly related to AP-SA02: one with transient liver enzyme elevation and another with hypersensitivity that resolved after discontinuation of vancomycin.
Significant Clinical Efficacy
The primary clinical efficacy endpoint showed a statistically significant increase in investigator-assessed responder rate at Test of Cure (TOC) for AP-SA02 (day 12) in treated subjects (88%) versus placebo (58%) (p = 0.047).
More impressively, at TOC for BAT and at end of study (EOS), 100% of the AP-SA02 treated subjects had clinically responded (p = 0.017) compared to only 75% in the placebo group. The 25% non-responder rate in the placebo group was due to either relapse or treatment failure, consistent with rates reported in recent phase 3 trials.
The Clinical Efficacy Adjudication Committee, comprised of leading experts in the bacteremia field, confirmed these findings, noting that subjects who received placebo had a 22% and 25% non-responder rate at TOC with BAT and at EOS, respectively, while 100% of subjects who received AP-SA02 clinically responded (p = 0.025 at TOC BAT; p = 0.020 at EOS).
Efficacy Against Resistant Strains
Notably, AP-SA02 demonstrated efficacy regardless of whether subjects were infected with methicillin-sensitive S. aureus (MSSA) or methicillin-resistant S. aureus (MRSA). All subjects infected with MRSA and treated with AP-SA02 and BAT cleared their infection by TOC for BAT with no evidence of relapse through EOS, compared to the relapse rate observed with BAT alone.
"This clinical trial is groundbreaking in two fundamental ways: firstly, this is the first clear evidence in a randomized controlled trial of the efficacy of phage against a serious systemic pathogen that is responsible for significant morbidity and mortality in the United States, and secondly, Armata was able to successfully produce high titer phage with high purity allowing for repetitive IV administration every six hours without significant safety concerns," Dr. Birx explained.
Biomarker Improvements
Supporting the clinical outcomes, researchers observed faster time to negative blood cultures and decline of key predictors of mortality and complications in S. aureus bacteremia, including interleukin-10 and C-reactive protein, in subjects treated with AP-SA02.
The trial results suggest that AP-SA02 can effectively target different sites of infection, penetrate biofilms, and infect and lyse S. aureus bacteria, independent of antibiotic resistance patterns and infection site.
Manufacturing Capabilities and Future Plans
Armata has developed in-house manufacturing capabilities at its cGMP facility in California, with capacity to produce over 10,000 full courses of phage therapy annually. This domestic manufacturing capability aligns with efforts to onshore critical biomedical technologies.
The company has received substantial support for this program, including a total of $26.2 million in non-dilutive funding from the U.S. Department of Defense through the Medical Technology Enterprise Consortium and managed by the Naval Medical Research Command.
Based on these promising results, Armata plans to move rapidly toward initiating a pivotal trial. The company anticipates that the data from the diSArm study will inform the optimal dose of AP-SA02 for future efficacy studies.
Implications for Phage Therapy
The diSArm trial represents a significant milestone in the development of bacteriophage therapeutics for systemic bacterial infections. As antibiotic resistance continues to pose a global health threat, these results suggest that phage therapy could provide a valuable alternative or complementary approach to conventional antibiotics.
"These data, including the favorable safety profile of AP-SA02, warrant that we move as rapidly as possible towards initiation of a pivotal trial," Dr. Birx concluded, acknowledging the patients who participated in the study, the trial sites, and the Armata team, as well as the support from Innoviva and the U.S. Department of Defense.
The success of AP-SA02 in this trial marks an important step forward in addressing the growing challenge of antibiotic-resistant infections and potentially offers new hope for patients with complicated S. aureus bacteremia, a condition associated with significant morbidity and mortality.
