tozorakimab Advanced Drug Monograph

Tozorakimab Report

Name: tozorakimab Name (English): tozorakimab

Description: Tozorakimab (MEDI-3506) is a high-affinity human immunoglobulin G1 monoclonal antibody that neutralizes interleukin-33 (IL-33). IL-33 is a cytokine involved in inflammatory processes. By blocking IL-33 signaling through its receptors ST2 and RAGE/EGFR, tozorakimab aims to reduce inflammation and epithelial dysfunction.

Mechanism of Action: Tozorakimab inhibits both reduced (IL-33red) and oxidized (IL-33ox) forms of IL-33, preventing them from binding to their respective receptors (ST2 and RAGE/EGFR complex). This action reduces downstream signaling that leads to inflammation.

Investigational Uses: Tozorakimab is currently under investigation for the treatment of various inflammatory conditions, including:

• Chronic Obstructive Pulmonary Disease (COPD)
• Asthma
• Viral Lung Infections
• Atopic Dermatitis (discontinued)
• Diabetic Nephropathies (discontinued)

Administration:

• COPD: Subcutaneous injection at regular intervals.
• Viral Lung Infections: Single intravenous (IV) dose.

Clinical Trial Status: Tozorakimab is in various phases of clinical development:

• Phase 3: COPD, Respiratory Insufficiency, Viral Lung Infection.
• Phase 2: Asthma.
• Phase 1: Pharmacokinetic trial in healthy adults.

Potential Benefits Studied:

• Reduction in COPD exacerbations.
• Improvement in lung function (FEV1).
• Enhanced quality of life for COPD patients.
• Decreased need for rescue medications in COPD.
• Prevention of death or progression to mechanical ventilation in severe viral lung infections.
• Reduction in duration of hospital stays and ICU time for viral lung infections.

Ongoing Phase 3 Trials (Examples):

• OBERON (NCT06040086): Efficacy and safety in symptomatic COPD with a history of exacerbations.
• PROSPERO (NCT05742802): Long-term efficacy and safety in COPD patients with a history of exacerbations (extension study).
• NCT05624450: Efficacy and safety in patients hospitalized for viral lung infection requiring supplemental oxygen.

Pharmacokinetics and Immunogenicity: Studies are evaluating how tozorakimab moves through the body (absorption, distribution, elimination) and the body's immune response to the drug (immunogenicity).

Safety: Tozorakimab has been reported to be well-tolerated in early-stage trials, with no major safety concerns raised to date. However, ongoing trials continue to monitor for adverse events.

Note: Tozorakimab is an investigational drug and is not yet approved for general use. Information presented here is based on publicly available data from clinical trials and research publications.