- |||||||||| Clinical, Journal: Towards precision medicine in COPD: Targeting type 2 cytokines and alarmins. (Pubmed Central) - Jul 2, 2024
300 eosinophils/?L treated with dupilumab (anti-IL-4R?)...Several ongoing RCTs are evaluating the efficacy and safety of anti-TSLP (tezepelumab), anti-IL-33 (itepekimab, tozorakimab), and anti-ST2 (astegolimab) in patients with COPD, who experience exacerbations. In conclusion, targeting T2 inflammation or epithelial-derived alarmins might represent a step forward in precision medicine for the treatment of a subset of COPD.
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Clinical, P1 data, PK/PD data, Journal: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Tolerability After Subcutaneous Administration of Tozorakimab in Healthy Chinese Participants. (Pubmed Central) - Jun 1, 2024 P1 There were no clinically relevant trends over time in clinical laboratory (hematology, clinical chemistry, and urinalysis), electrocardiogram, or vital sign parameters in any treatment group. Overall, tozorakimab demonstrated dose-dependent systemic exposure in healthy Chinese participants and was well tolerated, with no safety concerns identified in this study.
- |||||||||| Review, Journal: Advancements in Diabetic Kidney Disease Management: Integrating Innovative Therapies and Targeted Drug Development. (Pubmed Central) - May 20, 2024
Emerging agents including GLP-1 agonists, anti-inflammatory agents like bardoxolone, and mineralocorticoid receptor antagonists show promise in mitigating DKD progression. Many novel therapies including monoclonal antibodies CSL346, Lixudebart, and tozorakimab, mesenchymal stem/stromal cell infusion, and cannabinoid-1 receptor inverse agonism via INV-202 are currently in clinical trials and present opportunities for further drug development.
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Distinct Pharmacological Profiles of IL-33 Antibodies (San Diego Convention Center, Area F (Hall A-B2, Ground Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_3239; From the range of IL-33 antibodies tested, the ability to inhibit IL-33ox biological effects was unique to tozorakimab and appeared to be dependent on epitope, which is distinct for tozorakimab versus other IL-33 antibodies. Tozorakimab is under clinical investigation to reduce excess inflammation and epithelial remodelling in IL-33-driven disease.
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Trial completion: A Phase 2b Diabetic Kidney Disease Study (clinicaltrials.gov) - Jun 18, 2023 P2b, N=609, Completed, Trial completion date: May 2024 --> Mar 2025 | Trial primary completion date: May 2024 --> Mar 2025 Active, not recruiting --> Completed
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca, Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
FRONTIER-1: PHASE 2B STUDY OF IL-33 BLOCKADE IN DIABETIC KIDNEY DISEASE (Focussed Oral Room 1) - May 4, 2023 - Abstract #ERAEDTA2023ERA_EDTA_1035; P2b This hypothesis is currently being tested in the FRONTIER-1 phase 2b clinical study. To identify the patients most likely to benefit from immunomodulatory treatment with tozorakimab, the study will conduct a retrospective analysis of albuminuria and inflammatory biomarkers.
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Associations of the IL-33 Signalling Pathway With Poor Clinical Outcomes and Lung Pathology in Patients With Respiratory Virus Infections at Risk of Acute Respiratory Failure (Walter E. Washington Convention Center, Room 102 A-B (Street Level)) - Mar 25, 2023 - Abstract #ATS2023ATS_4203; Tozorakimab driven endothelial cell transcriptomic signatures demonstrated strong associations of the IL-33-ST2 pathway with broad respiratory viral infections (including influenza, HRV, RSV) and pathological mechanisms including cell adhesion, hyper-inflammation and coagulation.Conclusions In summary, we provide a scientific rationale for targeting IL-33 in COVID-19 and other severe viral respiratory tract infections. Early intervention with tozorakimab has the potential to reduce IL-33-driven hyper-inflammation and remodelling of the lung alveolar capillary membrane and thereby improve clinical outcomes in hospitalised patients at risk of progressing to ARF.
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Trial completion date, Trial primary completion date: TILIA: Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen (clinicaltrials.gov) - Mar 24, 2023 P3, N=2352, Recruiting, Early intervention with tozorakimab has the potential to reduce IL-33-driven hyper-inflammation and remodelling of the lung alveolar capillary membrane and thereby improve clinical outcomes in hospitalised patients at risk of progressing to ARF. Trial completion date: May 2024 --> Dec 2024 | Trial primary completion date: May 2024 --> Dec 2024
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Enrollment closed, Trial primary completion date: FRONTIER-4: A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess MEDI3506 in Participants With COPD and Chronic Bronchitis (clinicaltrials.gov) - Mar 13, 2023 P2, N=137, Active, not recruiting, Not yet recruiting --> Recruiting | Trial primary completion date: Jun 2025 --> Sep 2025 Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2023 --> May 2023
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Enrollment closed: A Phase 2b Diabetic Kidney Disease Study (clinicaltrials.gov) - Oct 21, 2022 P2b, N=609, Active, not recruiting, Not yet recruiting --> Recruiting Recruiting --> Active, not recruiting
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Oxidised IL-33 signals via RAGE/EGFR to drive a COPD-associated phenotype (8F) - Jun 22, 2022 - Abstract #ERS2022ERS_2880; Tozorakimab (MEDI3506), a high-affinity human IgG1 monoclonal antibody, was used to inhibit IL-33 signalling...Gene set enrichment analysis showed that gene signatures defining the effects of IL-33ox were enriched in airway epithelia from patients with severe COPD. ConclusionOur data reveal a previously unknown IL-33ox–RAGE/EGFR epithelial signalling pathway, which governs key features of COPD and could be an attractive therapeutic target.
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Enrollment closed: Efficacy and Safety of MEDI3506 in Adult Subjects With Atopic Dermatitis (clinicaltrials.gov) - Apr 25, 2022 P2, N=145, Active, not recruiting, Tozorakimab is under clinical investigation to reduce excess inflammation and epithelial remodelling in IL-33-driven disease. Recruiting --> Active, not recruiting
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Safety, Pharmacokinetics and Immunogenicity of the Anti-Interleukin-33 Antibody, Tozorakimab: Results of a Phase 1 Study in Healthy Adults and Patients with Chronic Obstructive Pulmonary Disease (Room 9-10 (South Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_2308; P1, P2, P2 No impact of anti-drug antibodies was observed on safety.Conclusions In this study, tozorakimab was well-tolerated with no safety concerns. These data support progression to Phase 2 studies in COPD (NCT04631016), asthma (NCT04570657), atopic dermatitis (NCT04212169), diabetic kidney disease (NCT04170543) and COVID-19 (EudraCT: 2020-001736-95).
- |||||||||| tozorakimab (MEDI3506) / AstraZeneca
Trial completion date, Trial primary completion date: Efficacy and Safety of MEDI3506 in Adult Subjects With Atopic Dermatitis (clinicaltrials.gov) - Dec 6, 2021 P2, N=152, Recruiting, N=322 --> 144 | Trial completion date: Dec 2022 --> Jul 2023 | Trial primary completion date: Dec 2022 --> Jul 2023 Trial completion date: Mar 2022 --> Jul 2022 | Trial primary completion date: Mar 2022 --> Jul 2022
- |||||||||| MEDI3506 / AstraZeneca
[VIRTUAL] IL-33 as a Novel Target for the Treatment of Diabetic Kidney Disease () - Oct 17, 2021 - Abstract #KIDNEYWEEK2021KIDNEY_WEEK_2001; Conclusion Upregulation of IL-33 in diabetic kidney, generates localised chronic kidney inflammation through autocrine signalling in GECs and MCs. This data suggest that targeting IL-33 with MEDI3506 arises as a promising therapeutic intervention for DKD, currently in Ph2b trial.
|