Add on Exebacase to antibiotics Falls Short in Treating MRSA Bacteremia, reveals study
Staphylococcus aureus bacteremia, especially when caused by methicillin-resistant S. aureus (MRSA), poses a significant challenge in healthcare. Seeking innovative solutions, the DISRUPT study investigated the efficacy of exebacase, a first-in-class antistaphylococcal lysin, as an adjunct to standard-of-care antibiotics. However, the study faced unexpected challenges, prompting a closer look at the results and their implications.
The study was published in the journal of Clinical Infectious Diseases by Vance G. Fowler and colleagues. In this phase 3 superiority-design study, 259 patients with S. aureus bacteremia/endocarditis were randomized to receive either a single dose of IV exebacase or a placebo alongside standard-of-care antibiotics. The primary endpoint was the clinical response at Day 14 in the MRSA population.
• Surprisingly, the study was stopped for futility by the Data Safety Monitoring Board, as exebacase failed to enhance the clinical response at Day 14 in patients with MRSA bacteremia/endocarditis.
• Clinical response rates at Day 14 in the MRSA population were 50.0% for exebacase + antibiotics vs. 60.6% for antibiotics alone, with no statistically significant difference (P = 0.392).
• Notably, adverse events were similar across groups, and no hypersensitivity events related to exebacase were reported.
The DISRUPT study's unexpected outcome challenges the promising phase 2 data that demonstrated the potential of exebacase + antibiotics in MRSA bacteremia/endocarditis. The higher-than-expected clinical response rate in the antibiotics alone group further complicates the interpretation. Heterogeneity within the study population and the relatively small sample size might have contributed to imbalances in Day 14 clinical outcomes. These results emphasize the complexity of studying S. aureus bacteremia/endocarditis and provide crucial lessons for future research in this field.
The DISRUPT study highlights the need for caution in interpreting phase 2 data, emphasizing the importance of large, well-designed phase 3 trials. Future studies in S. aureus bacteremia/endocarditis should carefully consider population heterogeneity and adequately power the study to minimize the risk of imbalances in outcomes.
Reference:
Fowler, V. G., Das, A. F., Lipka-Diamond, J., Ambler, J. E., Schuch, R., Pomerantz, R., Cassino, C., Jáuregui-Peredo, L., Moran, G. J., Rupp, M. E., Lachiewicz, A. M., Kuti, J. L., Wise, R. A., Kaye, K. S., Zervos, M. J., & Nichols, W. G. Exebacase in addition to standard-of-care antibiotics for staphylococcus aureus bloodstream infections and right-sided infective endocarditis: A phase 3, superiority-design, placebo-controlled, randomized clinical trial (DISRUPT). Clinical Infectious Diseases,2024;ciae043. https://doi.org/10.1093/cid/ciae043
