CLINICAL TRIALS PROFILE FOR FETROJA

All Clinical Trials for FETROJA

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT05314764 ↗	Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis	Not yet recruiting	Indiana University Health Methodist Hospital	Phase 4	2022-06-01	There is established evidence that adult patients with Cystic Fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Cefiderocol is a newly approved broad spectrum intravenous siderophore cephalosporin antibiotic, which has potent in vitro activity against multidrug resistant Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter species, and Stenotrophomonas maltophilia, all pathogens implicated in CF pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of cefiderocol in 12 adult CF patients admitted for a pulmonary exacerbation at one of 4 participating hospitals in the US. Patients will remain on standard of care IV antibiotics and receive 4-6 doses of cefiderocol 2 grams infused over 3 hours every 6-8 hours, depending on kidney function. Blood will be sampled after the final dose to determine concentrations and pharmacokinetics of cefiderocol. Safety and tolerability will be assessed throughout the 2 day study.
NCT05314764 ↗	Cefiderocol Pharmacokinetics in Adult Patients With Cystic Fibrosis	Not yet recruiting	Keystone Bioanalytical, Inc.	Phase 4	2022-06-01	There is established evidence that adult patients with Cystic Fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Cefiderocol is a newly approved broad spectrum intravenous siderophore cephalosporin antibiotic, which has potent in vitro activity against multidrug resistant Pseudomonas aeruginosa, Burkholderia cepacia complex, Achromobacter species, and Stenotrophomonas maltophilia, all pathogens implicated in CF pulmonary exacerbations. This study will determine the pharmacokinetics and tolerability of cefiderocol in 12 adult CF patients admitted for a pulmonary exacerbation at one of 4 participating hospitals in the US. Patients will remain on standard of care IV antibiotics and receive 4-6 doses of cefiderocol 2 grams infused over 3 hours every 6-8 hours, depending on kidney function. Blood will be sampled after the final dose to determine concentrations and pharmacokinetics of cefiderocol. Safety and tolerability will be assessed throughout the 2 day study.
NCT04995835 ↗	Cefiderocol PK in Patients on ECMO	Recruiting	Shionogi Inc.	Phase 1	2021-07-16	Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary life-support for critically ill patients where blood is extracted from the vascular system and circulated by a mechanical pump while it is oxygenated and reinfused into the patient's circulation. It is well known that critically ill patients may experience alterations in antibiotic pharmacokinetics, and as a result, dosing modifications are generally required. There is a need to understand how ECMO circuits affect the pharmacokinetics and disposition of drugs. This study is designed to assess the pharmacokinetics of the new broad-spectrum antibiotic, Cefiderocol, in critically ill patient receiving ECMO.
NCT04995835 ↗	Cefiderocol PK in Patients on ECMO	Recruiting	Joseph L. Kuti, PharmD	Phase 1	2021-07-16	Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary life-support for critically ill patients where blood is extracted from the vascular system and circulated by a mechanical pump while it is oxygenated and reinfused into the patient's circulation. It is well known that critically ill patients may experience alterations in antibiotic pharmacokinetics, and as a result, dosing modifications are generally required. There is a need to understand how ECMO circuits affect the pharmacokinetics and disposition of drugs. This study is designed to assess the pharmacokinetics of the new broad-spectrum antibiotic, Cefiderocol, in critically ill patient receiving ECMO.
NCT04335539 ↗	Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of Cefiderocol in Hospitalized Pediatric Patients	Recruiting	Shionogi	Phase 2	2020-08-21	The primary objectives of this study are: - To assess the safety and tolerability of cefiderocol after single-dose administration in hospitalized paediatric patients 3 months to < 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections - To assess the pharmacokinetics (PK) of cefiderocol after single-dose administration of cefiderocol in hospitalized paediatric patients 3 months to < 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections - To assess the safety and tolerability of cefiderocol after multiple-dose administration in hospitalized paediatric patients 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections - To assess the PK of cefiderocol after multiple-dose administration in hospitalized paediatric patients 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
NCT04215991 ↗	Safety, Tolerability, and Pharmacokinetics of Cefiderocol in Hospitalized Pediatric Patients	Recruiting	Shionogi	Phase 2	2020-02-19	To assess the safety, tolerability, and pharmacokinetics (PK) of cefiderocol after single-dose administration in hospitalized pediatric patients 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections and after multiple-dose administration in hospitalized pediatric patients 3 months to < 18 years of age with suspected or confirmed complicated urinary tract infection (cUTI), hospital-acquired pneumonia (HAP), or ventilator-associated pneumonia (VAP).

Clinical Trial Conditions for FETROJA

Condition Name

Condition Name for FETROJA
Intervention	Trials
Complicated Urinary Tract Infection (cUTI)	2
Gram-negative Bacterial Infections	2
Hospital Acquired Pneumonia (HAP)	2
Sepsis	2

Condition MeSH

Condition MeSH for FETROJA
Intervention	Trials
Bacterial Infections	3
Pneumonia	3
Infections	2
Infection	2

Clinical Trial Locations for FETROJA

Trials by Country

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−

Trials by Country for FETROJA
Location	Trials
United States	6
Ukraine	2
Spain	2
Panama	1
Estonia	1

Trials by US State

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−

Trials by US State for FETROJA
Location	Trials
Connecticut	2
Texas	2
Pennsylvania	1
Indiana	1

Clinical Trial Progress for FETROJA

Clinical Trial Phase

Clinical Trial Phase for FETROJA
Clinical Trial Phase	Trials
Phase 4	2
Phase 2	2
Phase 1	1

Clinical Trial Status

Clinical Trial Status for FETROJA
Clinical Trial Phase	Trials
Recruiting	3
Not yet recruiting	2

Clinical Trial Sponsors for FETROJA

Sponsor Name

Sponsor Name for FETROJA
Sponsor	Trials
Shionogi	2
Shionogi Inc.	2
Rambam Health Care Campus	1

Sponsor Type

Sponsor Type for FETROJA
Sponsor	Trials
Other	12
Industry	4

Fetroja (Cefiderocol): Clinical Trials, Market Analysis, and Projections

Introduction

Fetroja, marketed as cefiderocol, is a novel siderophore cephalosporin antibiotic designed to combat multidrug-resistant Gram-negative bacterial infections. Here, we delve into the clinical trials, market analysis, and future projections for this critical antibiotic.

Clinical Trials Overview

Trial Design and Objectives

The clinical trials for Fetroja were meticulously designed to assess its efficacy and safety. For instance, in the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), a non-inferiority trial was conducted. This trial randomized patients 1:1 to receive either Fetroja or meropenem, both in combination with linezolid for at least 5 days. The primary efficacy endpoint was the all-cause mortality (ACM) rate at Day 14 in the modified intent-to-treat (ITT) population[1].

Key Endpoints and Outcomes

In the HABP/VABP trial, key secondary endpoints included Day-28 ACM and clinical cure rates. The trial demonstrated that Fetroja was non-inferior to meropenem in terms of ACM and clinical cure rates, highlighting its effectiveness against severe Gram-negative infections[1].

For complicated urinary tract infections (cUTIs), including pyelonephritis, Fetroja was compared to imipenem/cilastatin in a randomized, active-controlled, double-blind trial. The efficacy of Fetroja was established based on a composite of microbiological eradication and clinical response at the Test of Cure (TOC) visit. Fetroja showed a composite response rate of 72.6% compared to 54.6% for imipenem/cilastatin, indicating its superiority in certain aspects[4].

Pediatric Studies

Postmarketing studies are ongoing to evaluate the pharmacokinetics, safety, and tolerability of Fetroja in pediatric patients. These studies include an open-label, randomized trial in children from 3 months to less than 18 years of age with cUTIs and HABP/VABP, as well as a single-arm study in infants from birth to less than 3 months of age[2].

Market Analysis

Global Approval and Availability

Fetroja has obtained approval in several regions, including Japan, Europe, and the United States, where it is marketed under different brand names. It is also listed on the WHO Essential Medicines List, underscoring its global importance. Efforts are underway to improve access in low- and middle-income countries through partnerships with The Global Antibiotic Research and Development Partnership (GARDP) and the Clinton Health Access Initiative (CHAI)[3].

Sales Performance

Since its launch in 2020, Fetroja has contributed significantly to Shionogi's revenue. In fiscal 2023, the sales of Fetroja increased by 45.4% year-over-year, reflecting its growing market presence and demand. The drug's performance has helped stabilize Shionogi's revenue, making it less susceptible to fluctuations in the prevalence of specific infections[5].

Market Projections

Antimicrobial Resistance (AMR) Impact

The increasing threat of antimicrobial resistance (AMR) is expected to drive the demand for effective antibiotics like Fetroja. By 2050, AMR is projected to cause approximately 10 million deaths annually and have an economic impact of $100 trillion if effective measures are not taken. Fetroja's role in combating AMR is crucial, and its market is likely to expand as the need for such treatments grows[5].

Expansion and Partnerships

Shionogi is actively working on expanding Fetroja's availability to more countries, particularly through partnerships with GARDP and CHAI. As of 2023, Fetroja can be provided in 135 countries through these partnerships, indicating a significant global reach. This expansion is expected to further boost sales and market presence[5].

Competitive Landscape

In the market for antibiotics, Fetroja stands out due to its unique mechanism of action and efficacy against multidrug-resistant Gram-negative bacteria. While other antibiotics may face resistance issues, Fetroja's siderophore-mediated entry into bacterial cells makes it a valuable option. This competitive advantage is likely to sustain its market position and drive future growth[4].

Future Developments

Pipeline and Research

Shionogi continues to invest in research and development, with Phase 2a trials for new pipeline products scheduled to begin in fiscal 2025. The company's focus on infectious diseases, including the development of treatments for other viral and bacterial infections, is expected to enhance its overall portfolio and further stabilize revenue[5].

Regulatory and Access Initiatives

Efforts to improve access to Fetroja in various regions are ongoing. Regulatory approvals and partnerships with global health initiatives will continue to play a crucial role in expanding the drug's reach and ensuring its availability to patients in need.

Key Takeaways

• Clinical Efficacy: Fetroja has demonstrated non-inferiority to standard treatments in clinical trials for HABP/VABP and superiority in certain aspects for cUTIs.
• Global Approval: Approved in Japan, Europe, and the United States, with listings on the WHO Essential Medicines List.
• Market Performance: Significant revenue growth since its launch, contributing to Shionogi's stable revenue stream.
• AMR Impact: Expected to play a critical role in combating AMR, driving future demand.
• Expansion and Partnerships: Ongoing efforts to increase global availability through partnerships.

FAQs

What is Fetroja used for?

Fetroja (cefiderocol) is used to treat adults with complicated urinary tract infections (cUTIs), including pyelonephritis, and hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP)[4].

How does Fetroja work?

Fetroja works by using a siderophore-mediated mechanism to enter bacterial cells, where it inhibits cell wall synthesis, leading to bacterial death[4].

What are the key clinical trial findings for Fetroja?

Clinical trials have shown that Fetroja is non-inferior to meropenem for HABP/VABP and superior to imipenem/cilastatin in certain aspects for cUTIs[1][4].

Is Fetroja approved for pediatric use?

Currently, Fetroja is approved for use in adults. However, postmarketing studies are underway to evaluate its safety and efficacy in pediatric patients[2].

What is the market outlook for Fetroja?

The market outlook for Fetroja is positive, driven by its efficacy against multidrug-resistant infections and ongoing efforts to expand its global availability. The growing threat of AMR is expected to further increase demand for Fetroja[5].

What partnerships is Shionogi involved in to expand Fetroja's reach?

Shionogi is partnered with The Global Antibiotic Research and Development Partnership (GARDP) and the Clinton Health Access Initiative (CHAI) to improve access to Fetroja in low- and middle-income countries[3].

Sources

1. Fetroja® (cefiderocol) | HABP/VABP Clinical Data. Fetroja.
2. CENTER FOR DRUG EVALUATION AND RESEARCH. FDA.
3. Launch of the Gram-negative Bacterial Infection Treatment .... Shionogi.
4. Drug Trials Snapshot: FETROJA - FDA. FDA.
5. Future - Shionogi Inc.. Shionogi.