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<p>Cystic fibrosis is a monogenetic disease complicated by recurrent bacterial lung infections that require chronic antibiotics. <i>Pseudomonas aeruginosa</i> is an increasingly antibiotic-resistant pathogen associated with cystic fibrosis morbidity and mortality. Here, we describe the development of a three-phage cocktail (BX004-A) designed to target a wide range of <i>P. aeruginosa</i> strains. We evaluated BX004-A in Part 1 of a first-in-human double-blind placebo-controlled phase 1b/2a clinical trial, which included nine adult cystic fibrosis patients chronically infected with <i>P. aeruginosa</i> (NCT05010577). BX004-A met the primary endpoints of safety and tolerability. Exploratory endpoints included pharmacokinetics and <i>Pseudomonas aeruginosa</i> sputum density reduction. Efficient phage delivery to the lower respiratory tract was observed, and a potential reduction in <i>P. aeruginosa</i> sputum burden was noted in the phage arm. However, due to the study’s small sample size, definitive conclusions regarding efficacy are limited. These data pave the way toward further development of novel phage-based therapeutics in antibiotic-resistant pulmonary bacterial infections.</p>

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Phage therapy with nebulized cocktail BX004-A for chronic Pseudomonas aeruginosa infections in cystic fibrosis: a randomized first-in-human trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Iddo Weiner,
  • Maya Kahan-Hanum,
  • Nufar Buchstab,
  • Lior Zelcbuch,
  • Sharon Navok,
  • Irit Sherman,
  • Julian Nicenboim,
  • Tim Axelrod,
  • Dikla Berko-Ashur,
  • Maya Olshina,
  • Ron Mordoch,
  • Jagoda Jablonska,
  • Tamar Gera-Inbar,
  • Ilya Vainberg-Slutskin,
  • Britny Blumenfeld,
  • Hila Sberro-Livnat,
  • Ayelet Moses,
  • Hadas Nevenzel,
  • Inbal Levy-Saar,
  • Jenia Gold,
  • Meital Goldberg,
  • Nina Tchernorudsky,
  • Noa Ben-Yishay,
  • Tal Cohen,
  • Edith Kario,
  • Inesa Levovich,
  • Roman Safonov,
  • Yaron Tzur,
  • Yulia Zarchin,
  • Vered Lev,
  • Yifat Elharar,
  • Einav Safyon-Gartman,
  • Inbar Gahali-Sass,
  • Sailaja Puttagunta,
  • Xilla Ussery,
  • Regis Vilchez,
  • Urania Rappo,
  • Naomi Zak,
  • Myriam Golembo,
  • Ariel Cohen,
  • Jon Koff,
  • Eitan Kerem,
  • Rotem Sorek,
  • Merav Bassan

摘要

Cystic fibrosis is a monogenetic disease complicated by recurrent bacterial lung infections that require chronic antibiotics. Pseudomonas aeruginosa is an increasingly antibiotic-resistant pathogen associated with cystic fibrosis morbidity and mortality. Here, we describe the development of a three-phage cocktail (BX004-A) designed to target a wide range of P. aeruginosa strains. We evaluated BX004-A in Part 1 of a first-in-human double-blind placebo-controlled phase 1b/2a clinical trial, which included nine adult cystic fibrosis patients chronically infected with P. aeruginosa (NCT05010577). BX004-A met the primary endpoints of safety and tolerability. Exploratory endpoints included pharmacokinetics and Pseudomonas aeruginosa sputum density reduction. Efficient phage delivery to the lower respiratory tract was observed, and a potential reduction in P. aeruginosa sputum burden was noted in the phage arm. However, due to the study’s small sample size, definitive conclusions regarding efficacy are limited. These data pave the way toward further development of novel phage-based therapeutics in antibiotic-resistant pulmonary bacterial infections.