The FDA has placed a clinical hold on BiomX’s Phase IIb trial (NCT06998043) of BX004 for cystic fibrosis (CF).

According to the company, the hold specifically concerns a third-party nebulizer device used to deliver BX004. The drug candidate itself has previously been reviewed and cleared for investigational use with no concerns.

To address the agency’s concerns, BiomX has submitted additional independent data from the nebulizer’s manufacturer to address the FDA’s queries, with the expectation that the information will allow the hold to be lifted.

Despite the clinical hold in the United States, the European trial is unaffected, as all parts of the nebulizer device are CE marked and meet regulatory standards, allowing enrollment and dosing to proceed as planned.¹

What’s Next for the BX004 Trial Amid the FDA’s Device-Related Hold?

“We are actively engaged with the FDA to promptly address their queries regarding the third-party nebulizer,” said Jonathan Solomon, CEO, BiomX, in a press release. “Importantly, the FDA’s notification relates solely to the nebulizer, and we remain optimistic and confident that in response to the hold, we have provided the FDA with data that can satisfactorily support the use of the nebulizer and that this can be resolved promptly so that we may resume treating patients with cystic fibrosis in the US.”

Trial Design and Endpoints

• The randomized, double-blind, placebo-controlled, multicenter trial is currently evaluating BX004 in approximately 63 CF patients with chronic pseudomonas aeruginosa (PsA).
• Patients will be randomly assigned in a 2:1 ratio to receive either BX004 or placebo via inhalation twice daily for eight weeks.
• The primary endpoint of the trial is change in sputum PsA burden at eight weeks.
• Key secondary endpoints include, but are not limited to, change in lung function at days eight, 29, 43, 57, 85, three months post-dose, and six months post-dose; change in sputum PsA burden; the efficacy of BX004 in achieving negative sputum cultures for PsA; and the incidence of treatment-emergent adverse events.^2,3

BX004 Background and Regulatory Status

BiomX describes BX004 as a fixed multi-phage therapy. Earlier Phase Ib/IIa trials have shown that the treatment is safe, well-tolerated, and biologically active, demonstrating improved lung function and reduced bacterial burden in patients with lower baseline forced expiratory volume in one second. The treatment has also received FDA Fast Track and Orphan Drug designations.³

The news of BiomX’s clinical hold comes amid heightened regulatory scrutiny in the biotech sector. Last month, the FDA requested that Sarepta Therapeutics place its limb-girdle muscular dystrophy trials for Elevidys on clinical hold following multiple patient deaths, and initially recommended halting shipments of the therapy. The agency later lifted the shipment restriction for ambulatory patients after determining that the third death initially linked to Elevidys was unrelated to the treatment.⁴

Cystic Fibrosis Overview

• According to the American Lung Association, approximately 40,000 people in the United States are currently living with CF.
• An estimated one in every 30 people in the United States is a carrier of CF.
• The global prevalence of CF is around 100,000 people.
• While it is most common in White people, CF can affect people of all races and ethnicities.5
• The Cystic Fibrosis Foundation estimates that nearly 1,000 new cases of CF are diagnosed each year.
• Close to 75% of all cases are diagnosed by the time patients have reached two years of age.
• Sixty percent of patients with CF are aged 18 years or older.⁶

“BiomX remains committed to providing timely updates and full transparency to patients, physicians, and investors as the situation develops,” concluded Solomon, in the press release.

References

1. BiomX Provides Update on BX004 Phase 2b Trial for the Treatment of Patients with Cystic Fibrosis. GlobeNewswire. August 19, 2025. Accessed August 20, 2025. https://www.globenewswire.com/news-release/2025/08/19/3135672/0/en/BiomX-Provides-Update-on-BX004-Phase-2b-Trial-for-the-Treatment-of-Patients-with-Cystic-Fibrosis.html
2. Study With Phage for CF Subjects With Pseudomonas Lung Infection. Clinicaltrials.gov. Accessed August 20, 2025. https://clinicaltrials.gov/study/NCT06998043
3. BiomX Announces Successful Initiation of Phase 2b Trial with First Patient Dosed in BX004 Program in Patients with Cystic Fibrosis. GlobeNewswire. July 14, 2025. Accessed August 20, 2025. https://www.globenewswire.com/news-release/2025/07/14/3114776/0/en/BiomX-Announces-Successful-Initiation-of-Phase-2b-Trial-with-First-Patient-Dosed-in-BX004-Program-in-Patients-with-Cystic-Fibrosis.html
4. Vinay Prasad’s FDA Departure Follows Controversy Over Drug Rejections. PharmExec. July 30, 2025. Accessed August 20, 2025. https://www.pharmexec.com/view/vinay-prasad-fda-departure-controversy-drug-rejections
5. Learn About Cystic Fibrosis. American Lung Association. Accessed August 20, 2025. https://www.lung.org/lung-health-diseases/lung-disease-lookup/cystic-fibrosis/learn-about-cystic-fibrosis#:~:text=There%20are%20about%2040%2C000%20people,CF%2C%20but%20treatment%20is%20available.
6. About Cystic Fibrosis. Cystic Fibrosis Foundation. Accessed August 20, 2025. https://www.cff.org/intro-cf/about-cystic-fibrosis#:~:text=According%20to%20the%20Cystic%20Fibrosis,fibrosis%20population%20is%20over%2018.