- |||||||||| Journal: Targeting downstream type 2 cytokines or upstream epithelial alarmins for severe asthma. (Pubmed Central) - Jun 15, 2022
Biologics, including omalizumab, mepolizumab, benralizumab, and dupilumab, targeting downstream IgE, cytokines IL-5, and IL-4/13, respectively, have shown promising effects in terms of reduction in annualized asthma exacerbation rates (AER), oral corticosteroid-sparing effects, improvements in forced expiratory volume in 1 second, and improved Asthma Control Questionnaire scores...Instead of blocking downstream cytokines, targeting upstream epithelial alarmins, including IL-33, thymic stromal lymphopoietin (TSLP), and IL-25, has been proposed to tackle the immunologic heterogeneity of asthma. This review article aims to pragmatically summarise the latest key clinical data on anti-alarmin therapies in severe asthma and put these findings into context with regards to currently available downstream cytokine blockers.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Review, Journal: Targeting TSLP in Asthma. (Pubmed Central) - Jun 11, 2022
Tezepelumab, the TSLP inhibitor farthest along in clinical development, is a human monoclonal antibody (IgG2λ) that binds specifically to TSLP, preventing interactions with its heterodimeric receptor...These data strengthen the notion that anti-TSLP elicits broad inhibitory effects on pathways that are key to asthma inflammation rather than on narrower inhibition of individual downstream factors. This review presents the rationale for targeting TSLP to treat asthma, as well as the clinical effects of TSLP blockade on asthma outcomes, biomarkers of disease activity, airway inflammation, lung physiology, and patient symptoms.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Review, Journal: Tezepelumab compared with other biologics for the treatment of severe asthma: a systematic review and indirect treatment comparison. (Pubmed Central) - Jun 9, 2022
This trend was consistent in the subgroup and sensitivity analyses. As with the primary NMA, the STC results did not demonstrate any significant differences between biologics, but point estimates were favorable towards tezepelumab.LIMITATIONS Heterogeneity between trials was observed among eligibility criteria and clinically important patient characteristics; however, impact on findings is expected to be low, based on consistency across analyses.CONCLUSIONS Findings from both ITCs (NMA and STC) support the use of tezepelumab in a broad patient population of severe uncontrolled asthma of any phenotype.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Biomarker, Journal: Baseline type 2 biomarker levels and response to tezepelumab in severe asthma. (Pubmed Central) - Jun 8, 2022
P2
At baseline, positive correlations between specific T2 inflammatory biomarkers were observed. Tezepelumab reduced multiple T2 inflammatory biomarkers, which indicates decreased airway inflammation, and reduced exacerbations irrespective of baseline T2 biomarker profiles in patients with severe asthma.
- |||||||||| Dupixent (dupilumab) / Sanofi, Regeneron, Tezspire (tezepelumab) / AstraZeneca, Amgen
Review, Journal: Dupilumab and tezepelumab in severe refractory asthma: new opportunities. (Pubmed Central) - Jun 8, 2022
Similar results were reported with tezepelumab that, differently from dupilumab, acts irrespectively on eosinophilic or non-eosinophilic phenotype. In this review, we provide an overview of the most important highlights regarding dupilumab and tezepelumab characteristics and mechanism of action with a critical review of the principal results of clinical (Phase II and III) studies concluded and those still in progress.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Trial completion date, Trial primary completion date: WAYPOINT: Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (clinicaltrials.gov) - Jun 8, 2022
P3, N=400, Recruiting,
In this review, we provide an overview of the most important highlights regarding dupilumab and tezepelumab characteristics and mechanism of action with a critical review of the principal results of clinical (Phase II and III) studies concluded and those still in progress. Trial completion date: Apr 2024 --> Oct 2024 | Trial primary completion date: Feb 2024 --> Aug 2024
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Journal: The effectiveness and value of tezepelumab for severe asthma. (Pubmed Central) - May 3, 2022
No abstract available DISCLOSURES: Drs Rind, Campbell, Pearson, Ms Herce-Hagiwara, Ms Fluetsch, and Ms Herron-Smith report grants from Arnold Ventures; Kaiser Foundation Health Plan, Inc; The Patrick and Catherine Donaghue Medical Research Foundation; Blue Cross Blue Shield of Massachusetts; and California Healthcare Foundation during the course of this study.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Journal: Tezspire Approved for Severe Asthma. (Pubmed Central) - Apr 28, 2022
These findings further support the benefits of tezepelumab in a broad population of patients with severe, uncontrolled asthma. Tezepelumab-ekko (Tezspire) has been approved by the Food and Drug Administration as an add-on maintenance therapy for people ages 12 years and older with severe asthma symptoms not controlled by current medication.The drug must be given subcutaneously by a health care provider.
- |||||||||| Review, Journal: Specific Therapy for T2 Asthma. (Pubmed Central) - Apr 24, 2022
Seemingly under study and promising, are anti-interleukin-33 (itepekimab) and anti-suppressor of tumorigenicity-2 (astegolimab). With this study, we want to provide an overview of these drugs, paying particular attention to their mechanism of action, the main endpoints reached in clinical trials, the main results obtained in real life and some unclear points regarding their usage.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Trial completion date, Trial primary completion date: COURSE: Tezepelumab COPD Exacerbation Study (clinicaltrials.gov) - Apr 13, 2022
P2a, N=338, Recruiting,
With this study, we want to provide an overview of these drugs, paying particular attention to their mechanism of action, the main endpoints reached in clinical trials, the main results obtained in real life and some unclear points regarding their usage. Trial completion date: Jul 2024 --> Mar 2024 | Trial primary completion date: Apr 2024 --> Dec 2023
- |||||||||| Dupixent (dupilumab) / Sanofi, Regeneron
Journal: A mathematical model to identify optimal combinations of drug targets for dupilumab poor responders in atopic dermatitis. (Pubmed Central) - Apr 9, 2022
Our model identified IL-13 as a potential predictive biomarker to stratify dupilumab good responders, and simultaneous inhibition of IL-13 and IL-22 as a promising drug therapy for dupilumab poor responders. This model will serve as a computational platform for model-informed drug development for precision medicine, as it allows evaluation of the effects of new potential drug targets and the mechanisms behind patient variability in drug response.
- |||||||||| Clinical, P2 data, P3 data, Review, Journal: Review and analysis of biologic therapies currently in phase II and phase III clinical trials for atopic dermatitis. (Pubmed Central) - Apr 8, 2022
Further assessment of tezepelumab and etokimab are needed to assess their safety and efficacy in patients with moderate-to-severe AD. Tralokinumab, lebrikizumab, fezakinumab, nemolizumab, and GBR 830 are effective treatment options for adults with moderate-to-severe AD, but further large-scale studies are needed to confirm their efficacy as monotherapy in children with moderate-to-severe AD.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Journal: Tezepelumab-ekko. (Pubmed Central) - Apr 5, 2022
Tralokinumab, lebrikizumab, fezakinumab, nemolizumab, and GBR 830 are effective treatment options for adults with moderate-to-severe AD, but further large-scale studies are needed to confirm their efficacy as monotherapy in children with moderate-to-severe AD. No abstract available
- |||||||||| Xolair (omalizumab) / Roche, Novartis
Clinical, Review, Journal: Emerging treatments for chronic urticaria. (Pubmed Central) - Mar 29, 2022
As the pipeline addresses different targets, study results will give deeper insights into the pathomechanisms of CU. Hopefully, in the next future additional approved and also more targeted approaches will be available.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Review, Journal: Tezepelumab: First Approval. (Pubmed Central) - Mar 24, 2022
Tezepelumab received orphan drug designation for the treatment of eosinophilic oesophagitis in October 2021 in the USA, and is undergoing clinical development for the treatment of COPD, CRSwNP and chronic spontaneous urticaria. This article summarizes the milestones in the development of tezepelumab leading to this first approval for the add-on maintenance treatment of patients aged ≥ 12 years with severe asthma.
- |||||||||| Xolair (omalizumab) / Roche, Novartis
Review, Journal: A pragmatic guide to choosing biologic therapies in severe asthma. (Pubmed Central) - Mar 18, 2022
Omalizumab is an anti-IgE mAb and is licensed in severe allergic asthma...Three biologics target the interleukin (IL)-5-eosinophil pathway, including mepolizumab and reslizumab that target IL-5 itself, and benralizumab that targets the IL-5 receptor (IL-5R-α)...Dupilumab targets the IL-4 receptor and like mepolizumab and benralizumab is effective at reducing exacerbation rate as well as oral corticosteroid requirements...Tezepelumab is an anti-TSLP (thymic stromal lymphopoietin) mAb that has recently completed phase 3 trials demonstrating significant reductions in exacerbation rate even at lower T2 biomarker thresholds...The presence of allergic and/or eosinophilic comorbidities, such as atopic dermatitis, nasal polyposis or eosinophilic granulomatosis with polyangiitis, that may additionally benefit by the choice of biologic should also be taken into consideration, as should patient preferences which may include dosing frequency. To date, all biologics have been shown to have excellent safety profiles.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Trial completion date, Trial primary completion date: COURSE: Tezepelumab COPD Exacerbation Study (clinicaltrials.gov) - Mar 16, 2022
P2a, N=338, Recruiting,
To date, all biologics have been shown to have excellent safety profiles. Trial completion date: Aug 2023 --> Jul 2024 | Trial primary completion date: May 2023 --> Apr 2024
- |||||||||| Xolair (omalizumab) / Roche, Novartis
Review, Journal: Eosinophilic airway diseases: basic science, clinical manifestations and future challenges. (Pubmed Central) - Mar 8, 2022
One example of such a registry is the NORdic Dataset for aSThmA Research (NORDSTAR), a longitudinal population-based dataset containing all 3.3 million individuals with asthma from four Nordic countries (Denmark, Finland, Norway and Sweden). Large-scale, real-world registry data such as those from Nordic countries may provide important information regarding the progression of eosinophilic asthma, in addition to clinical characteristics or biomarkers that could allow targeted treatment and ensure optimal patient outcomes.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
TEZSPIRE: A New Approach (Sheraton, Third Level, Phoenix Ballroom C) - Mar 5, 2022 - Abstract #AAAAI2022AAAAI_2373;
Speaker: Dr. Joel Hartman
- |||||||||| Xolair (omalizumab) / Roche, Novartis
Review, Journal: The use of biologics in food allergy. (Pubmed Central) - Mar 1, 2022
The ever better knowledge of the mechanisms of food allergy allowing these developments will improve not only the perspective of patients with the most serious immediate food allergies such as anaphylaxis, but also those of patients with related diseases such as atopic dermatitis, eosinophilic esophagitis, and EGIDs. Biologics are also intended to complement OIT strategies that have developed over the years.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Journal: Tezepelumab (Tezspire) for severe asthma. (Pubmed Central) - Feb 23, 2022
Biologics are also intended to complement OIT strategies that have developed over the years. No abstract available
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Clinical Responses to Treatment with Tezepelumab Among Patients with Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study (Room 3006/3008 (West Building, Level 3), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_3513;
P3
The proportion of on-treatment complete responders was higher in the tezepelumab group (48.2%) than in the placebo group (25.3%), with an OR of 2.78 (95% CI: 2.05-3.77) (Table).CONCLUSIONSA greater proportion of tezepelumab-treated patients with severe, uncontrolled asthma achieved on-treatment clinical responses than placebo-treated patients, with nearly half experiencing a complete response to treatment across measures of exacerbation reduction, asthma control, lung function and clinician assessment, at 2.8-fold higher odds than with placebo. These data further support the efficacy of tezepelumab in patients with severe, uncontrolled asthma.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Tezepelumab Reduces Biomarkers of Airway Remodeling, MMP-10 and MMP-3: Exploratory Results from the Phase 3 NAVIGATOR Study (Room 3006/3008 (West Building, Level 3), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_2264;
P3
Compared with placebo, MMP-10 levels were reduced from baseline by 12.09% (95% CI: 8.48-15.56) at week 2 and by 18.58% (95% CI: 14.38-22.58) at week 52 in the tezepelumab group, and MMP-3 levels were reduced from baseline by 7.67% (95% CI: 3.14-11.98) at week 2 and by 11.44% (95% CI: 5.96-16.61) at week 52 in the tezepelumab group (Figure).CONCLUSIONSConsistent with previous findings from the phase 2b PATHWAY study, tezepelumab treatment led to a rapid and sustained decrease from baseline in MMP-10 levels and a progressive decrease from baseline in MMP-3 levels over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. These findings suggest that inhibition of TSLP-driven airway inflammation with tezepelumab reduces levels of MMP-10 and MMP-3, which may be associated with changes in the local airway matrix.
- |||||||||| Effect of Biologics on Allergic Response and Airway Hyperresponsiveness: A Systematic Literature Review (Area I, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_823;
Tezepelumab also consistently attenuated nonspecific AHR to methacholine or mannitol. These findings provide further insight into the mechanisms of AHR and the clinical benefits of asthma biologics and suggest that tezepelumab may broadly target mediators or cells involved in asthma inflammation.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Journal: ASP7266, a novel antibody against human thymic stromal lymphopoietin receptor for the treatment of allergic diseases. (Pubmed Central) - Feb 17, 2022
The inhibitory effects of ASP7266 and the control antibody tezepelumab on TSLP and TSLPR interactions were investigated using a proliferation assay with TSLP stimulation and a chemokine production assay...Here we show that the anti-TSLPR antibody, ASP7266, exhibited excellent pharmacological activity in preclinical studies. Therefore, ASP7266 has the potential to be a promising treatment option for patients with allergic disorders.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma with Respiratory Comorbidities: Results from the Phase 3 NAVIGATOR Study (Convention Center, North Building, 100 Level, 120 Concourse) - Feb 4, 2022 - Abstract #AAAAI2022AAAAI_1658;
P3
Compared with placebo, tezepelumab reduced the AAER over 52 weeks by 54% (95% CI, 33-68) and 56% (95% CI, 46-65), respectively, in patients with and without chronic sinusitis; by 58% (95% CI, 47-67) and 50% (95% CI, 30-64), respectively, in patients with and without rhinitis; by 79% (95% CI, 54-91) and 54% (95% CI, 44-62), respectively, in patients with and without aspirin sensitivity; and by 85% (95% CI, 66-94) and 53% (95% CI, 43-61), respectively, in patients with and without NSAID sensitivity. NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Tezepelumab Reduces Exacerbations Across All Seasons in Patients with Severe, Uncontrolled Asthma: Results from the Phase 3 NAVIGATOR Study (Convention Center, North Building, 100 Level, Room 120B) - Feb 4, 2022 - Abstract #AAAAI2022AAAAI_1386;
P3
NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. In adults and adolescents with severe, uncontrolled asthma, treatment with tezepelumab consistently reduced exacerbations across all seasons compared with placebo.
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