Tozorakimab is a new therapeutic agent offering a targeted approach to managing certain inflammatory conditions. This investigational agent addresses underlying biological pathways involved in disease progression. Its development aims to provide more effective treatments for patients, reflecting ongoing efforts to expand available therapies.
What Tozorakimab Is
Tozorakimab is a human monoclonal antibody (IgG1 type), previously known as MEDI3506. It is engineered to specifically recognize and bind to a particular target molecule in the body, modulating biological processes implicated in various diseases.
Its purpose is to interfere with inflammatory pathways that contribute to chronic conditions. Unlike broad-acting anti-inflammatory drugs, Tozorakimab interacts with a very specific protein. This targeted action aims to reduce inflammation and tissue dysfunction without affecting other necessary biological functions.
Conditions It Targets
Tozorakimab is being investigated for its potential to treat inflammatory diseases where the interleukin-33 (IL-33) pathway is involved. A primary focus is moderate-to-severe chronic obstructive pulmonary disease (COPD), especially in patients with chronic bronchitis. COPD is a progressive lung disease marked by persistent respiratory symptoms and airflow limitation, often due to chronic inflammation.
Clinical trials have also explored Tozorakimab in diabetic kidney disease (DKD), moderate-to-severe atopic dermatitis (AD), and moderate-to-severe asthma. These conditions involve underlying inflammatory processes that Tozorakimab aims to modulate by targeting a specific inflammatory mediator.
How It Works
Tozorakimab neutralizes interleukin-33 (IL-33), a cytokine released by damaged cells that signals the immune system. IL-33 exists in two forms: a reduced form (IL-33red) and an oxidized form (IL-33ox). Each form signals through different pathways, promoting inflammation and epithelial dysfunction.
Tozorakimab inhibits IL-33 activities through both its signaling pathways. It binds with high affinity to IL-33red, preventing its signaling via the ST2 receptor. By binding to IL-33red, Tozorakimab also prevents its oxidation into IL-33ox, inhibiting IL-33ox activity through the RAGE/EGFR complex. This dual mechanism dampens inflammatory signals initiated by IL-33.
Its Development Journey
Tozorakimab has progressed through clinical development, with multiple Phase 2 studies completed under the FRONTIER program. These studies investigated the drug’s efficacy, safety, and pharmacokinetics in conditions like diabetic kidney disease, atopic dermatitis, asthma, and chronic obstructive pulmonary disease. Doses ranged from 30 mg to 600 mg, administered subcutaneously every four weeks.
Tozorakimab was well tolerated across these Phase 2 trials, with no major safety concerns. Although the primary endpoint was not met in the overall FRONTIER-4 COPD study population, positive efficacy signals appeared in a subgroup of COPD patients at high risk of exacerbations. Several Phase 3 studies are now underway for Tozorakimab in COPD, indicating its continued advancement towards potential regulatory approval.