- |||||||||| Review, Journal: Monoclonal antibodies in the management of asthma: Dead ends, current status and future perspectives. (Pubmed Central) - Dec 24, 2022
In addition, as available monoclonal antibody treatments have shown little benefit among patients with T-low asthma, research continues in this area, with several antibodies in development. This article summarizes the available pre-clinical and clinical data on new and emerging drugs for treating severe asthma, discusses discontinued treatments and outlines future directions in this area.
- |||||||||| Dupixent (dupilumab) / Sanofi, Regeneron, Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Retrospective data, Review, Journal: A comparison of the effectiveness of biologic therapies for asthma:a systematic review and network meta-analysis. (Pubmed Central) - Dec 24, 2022
Tezepelumab and dupilumab are effective at reducing exacerbations. For patients with low eosinophils, however, clinicians should probably be more judicious in use of biologics, including tezepelumab, since they probably do not confer substantial benefit.
- |||||||||| ecleralimab (CSJ117) / Novartis, MorphoSys, Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Review, Journal: Development of an inhaled anti-TSLP therapy for asthma. (Pubmed Central) - Dec 20, 2022
A Phase IIa proof of concept study, using allergen bronchoprovocation as a model for asthma exacerbations, found that ecleralimab was well-tolerated and reduced allergen-induced bronchoconstriction in adult patients with mild asthma. These results suggest ecleralimab may be a promising, new therapeutic class for asthma treatment.
- |||||||||| Dupixent (dupilumab) / Sanofi, Regeneron
Indirect comparison of dupilumab and tellers in patients with severe asthma (GOUDE 2) - Dec 14, 2022 - Abstract #CPLF2023CPLF_960;
P2, P3
In the week 52, the decrease in total serum IGE was significantly more important in the Dupilumab group than in the Tezepelumab group (-128.83 IU/ML [-250,89, -6.78]). Conclusion in patients with ≥ 2 exacerbations during the year preceding the study, the dupilumab has a more marked clinical response than the tezepelumab.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Review, Journal: Current summary of clinical studies on anti-TSLP antibody, Tezepelumab, in asthma. (Pubmed Central) - Dec 6, 2022
These results suggested that tezepelumab is a broad-target biologic, which is expected to be effective in patients with poorly controlled moderate to severe asthma regardless of the phenotype, although its efficacy in oral corticosteroids-dependent asthma, biological mechanism in non-type 2 phenotype, and long-term safety remain unknown. In this review, we summarize the results of clinical trials of tezepelumab in asthma and discuss the differences between tezepelumab and other biologics.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Review, Journal: Sounding the Alarmins - The Role of Alarmin Cytokines in Asthma. (Pubmed Central) - Dec 5, 2022
Blocking the function of TSLP inhibits allergen-induced responses including bronchoconstriction, airway hyperresponsiveness and inflammation, and subsequent clinical trials of an anti-TSLP monoclonal antibody, tezepelumab, in asthma patients demonstrated improvements in lung function, airway responsiveness, inflammation, and importantly, a reduction in the rate of exacerbations...To date there is no evidence that IL-25 blockade is beneficial in asthma. Despite considerable overlap in the cellular functions of IL-25, IL-33 and TSLP, they appear to have distinct roles in the immunopathology of asthma.
- |||||||||| Biomarker, Journal: Uncontrolled severe T2 asthma: Which biological to choose? A biomarker-based approach. (Pubmed Central) - Dec 2, 2022
Tezepelumab is approved by the Food and Drug Administration (FDA) in the United States and, recently, by the European Medicines Agency (EMA)...Because there are no direct comparisons between biological drugs, some biomarkers are used to choose between them, but they are not unbeatable. In this article, an algorithm to choose the first biological drug in a specific patient is proposed based on different study results and patient' characteristics.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Retrospective data, Review, Journal: Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. (Pubmed Central) - Nov 26, 2022
As for quality of life, different doses of the tezepelumab intervention group depicted non-significant improvement in the QoL, from 0.15 (95% CI: -0.09 to 0.38) for 70 mg, 0.18 (95% CI: -0.10 to 0.46) for 210 mg, 0.08 (95% CI: -0.16 to 0.32) for 280 mg as compared to the placebo. Tezepelumab significantly reduced exacerbation rates and improved FEV with an acceptable safety profile.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Effect of tezepelumab on a composite of severe asthma exacerbations and acute worsening events, CompEx, in the phase 3 NAVIGATOR study (Abbey, 4th floor) - Nov 15, 2022 - Abstract #BTSWM2022BTS_WM_307;
P3
This pre-specified analysis assessed the annualized rate of CompEx events over 52 weeks.Results Among 1059 treated patients, the annualized CompEx event rate was reduced by 55% (95% CI: 45–62) with tezepelumab versus placebo (table 1). The number of events and the annualized event rate were greater for CompEx than for severe asthma exacerbations; both were lower with tezepelumab than placebo (table 1).View this table:View inline S49 Table 1 CompEx events and severe exacerbations in NAVIGATORConclusion Tezepelumab reduced the CompEx event rate, a composite of severe asthma exacerbations and acute worsening events, versus placebo by a similar magnitude to the reduction in the rate of severe exacerbations, further demonstrating the efficacy of tezepelumab in adults and adolescents with severe, uncontrolled asthma.Please refer to page A210 for declarations of interest related to this .
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Efficacy of tezepelumab according to age at asthma onset in NAVIGATOR (Abbey, 4th floor) - Nov 15, 2022 - Abstract #BTSWM2022BTS_WM_306;
P3
Tezepelumab reduced the AAER versus placebo by 48% (95% CI: 29–62%), 63% (95% CI: 49–73%) and 56% (95% CI: 37–69%) in patients diagnosed with childhood-, adult- and late-onset asthma, respectively.Conclusion Tezepelumab reduced exacerbations versus placebo irrespective of age at asthma onset. These data further support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma.Please refer to page A209 for declarations of interest related to this .
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
DESTINATION: tezepelumab long-term safety and efficacy versus placebo in patients with severe, uncontrolled asthma (Abbey, 4th floor) - Nov 15, 2022 - Abstract #BTSWM2022BTS_WM_305;
P3
In those who initially received tezepelumab (n=74) or placebo (n=76) in SOURCE, incidence rates were 47.15 and 69.97 for AEs and 13.14 and 17.99 for SAEs, respectively. Tezepelumab reduced the AAER over 104 weeks versus placebo by 58% (95% CI: 49–65) and 39% (95% CI: 4–62) in NAVIGATOR and SOURCE patients, respectively, and reduced biomarker levels versus placebo.Conclusion Tezepelumab was well tolerated for up to 2 years and resulted in clinically meaningful reductions in asthma exacerbations.Please refer to page A209 for declarations of interest related to this .
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Tezepelumab reduces mucus plugging in patients with uncontrolled, moderate-to-severe asthma: the phase 2 CASCADE study (Abbey, 4th floor) - Nov 15, 2022 - Abstract #BTSWM2022BTS_WM_304;
P2
Reduction in mucus score with tezepelumab was correlated with improvements in these lung function parameters. S46 Figure 1 Change in mucus plugging scores from baseline to EOT in patients receiving (A) tezepelumab 210 mg Q4W and (B) placeboConclusion Tezepelumab is the first biologic shown to reduce mucus plugging in patients with moderate-to-severe, uncontrolled asthma in an RCT.Please refer to page A209 for declarations of interest related to this .
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen, fevipiprant (QAW039) / Novartis
Journal: Recent developments in the management of severe asthma. (Pubmed Central) - Nov 8, 2022
S46 Figure 1 Change in mucus plugging scores from baseline to EOT in patients receiving (A) tezepelumab 210 mg Q4W and (B) placeboConclusion Tezepelumab is the first biologic shown to reduce mucus plugging in patients with moderate-to-severe, uncontrolled asthma in an RCT.Please refer to page A209 for declarations of interest related to this . Fevipiprant is unlikely to be implemented as a future treatment for severe asthma, while tezepelumab may be a future treatment option for patients with severe asthma with and without eosinophilic inflammation https://bit.ly/3KE1BH4.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Review, Journal: Epithelial cell alarmin cytokines: Frontline mediators of the asthma inflammatory response. (Pubmed Central) - Nov 1, 2022
In support of these efforts, observations from the NAVIGATOR trial imply that targeting TSLP in patients with tezepelumab results in reduced asthma exacerbations, improved lung function and control of the disease...We also review in detail how alarmin-receptor/co-receptor interactions modulate downstream allergic inflammation. Current strategies which target alarmins, their efficacy and inflammatory phenotype will be discussed.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Journal: Tezepelumab in the Treatment of Uncontrolled Severe Asthma. (Pubmed Central) - Oct 29, 2022
In the case of a patient presenting with uncontrolled severe asthma with such comorbid conditions, it may be prudent to consider a biologic therapy that can target both. Tezepelumab has shown clinical utility in severe uncontrolled asthma regardless of phenotype, fulfilling the need for treatment options in individuals with severe, uncontrolled, noneosinophilic, and nonallergic asthma.
- |||||||||| Journal: Asthma Management in Adults. (Pubmed Central) - Oct 26, 2022
Focused updates to the EPR (Expert Panel Report) addressed limited, but specific questions relevant to asthma control. Future guidelines should include phenotype/endotype directed therapeutics to gain more precision directed treatment.
- |||||||||| Review, Journal: Monoclonal antibodies targeting small airways: a new perspective for biological therapies in severe asthma. (Pubmed Central) - Oct 19, 2022
Literature showing that biologic agents can also favorably improve small airway function is accumulating. In particular, anti-IL5 agents (mepolizumab and benralizumab) seems to have a greater impact on SAD as compared to other biological agents, but direct comparisons in prospective randomized controlled trials are lacking.In this mini-review article, we address the latest evidence on the effect of biological therapies on SAD in patients with severe asthma.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Trial completion: TRAILHEAD: Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma (clinicaltrials.gov) - Oct 17, 2022
P1, N=18, Completed,
In particular, anti-IL5 agents (mepolizumab and benralizumab) seems to have a greater impact on SAD as compared to other biological agents, but direct comparisons in prospective randomized controlled trials are lacking.In this mini-review article, we address the latest evidence on the effect of biological therapies on SAD in patients with severe asthma. Active, not recruiting --> Completed
- |||||||||| Review, Journal: Impact of Biologic Therapy on the Small Airways Asthma Phenotype. (Pubmed Central) - Oct 15, 2022
As opposed to topical inhaler therapy that might not adequately penetrate the small airways, it is perhaps more intuitive that systemic anti-inflammatory therapy with biologics targeting downstream cytokines and upstream epithelial anti-alarmins may offer a promising solution to SAD. Here we therefore aim to appraise the available evidence for the effect of anti-IgE, anti-IL5 (Rα), anti-IL4Rα, anti-TSLP and anti-IL33 biologics on small airways disease in patients with severe asthma.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
From CVID to AERD: Addressing Epithelial Barrier Dysfunction From Non-Type-2 To High-Type-2 Airway Inflammation (Exhibit Hall (Upper Concourse); Monitor 05) - Oct 10, 2022 - Abstract #ACAAI2022ACAAI_918;
Both experienced significant improvement of upper and lower respiratory symptoms with tezepelumab...TSLP released from epithelial barrier disruptions may be a commonality across asthma endotypes. This provides insight about the unified airway and creates exciting new possibilities for the treatment of both Type 2 and non-Type 2 respiratory diseases.
- |||||||||| A Case of Persistent Severe Asthma Despite Use of Multiple Biologics (Exhibit Hall (Upper Concourse); Monitor 05) - Oct 10, 2022 - Abstract #ACAAI2022ACAAI_913;
Discussion While biologics have revolutionized treatment options and greatly improved the lives of many asthmatics, they have side effect profiles that can limit their tolerability. Better understanding of difficult-to-control asthma and its underlying pathophysiology will help guide treatment options for these patients.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Efficacy Of Tezepelumab In Patients With Severe, Uncontrolled Asthma And High Baseline Blood Eosinophil Counts (Exhibit Hall (Upper Concourse); Monitor 12) - Oct 10, 2022 - Abstract #ACAAI2022ACAAI_669;
P3
Tezepelumab improved pre-BD FEV1 : least squares mean differences versus placebo were 0.26 L (95% confidence interval [CI]: 0.15–0.37), 0.21 L (95% CI: 0.02–0.40) and 0.41 L (95% CI: 0.13–0.69) in patients with baseline BECs ≥ 500, ≥ 750 and ≥ 1000 cells/μL, respectively. Conclusion Tezepelumab substantially reduced exacerbations and improved lung function versus placebo in patients with severe, uncontrolled asthma across all subgroups with high baseline BECs.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Effect Of Tezepelumab On Asthma Inflammatory Biomarker Levels Varies By Baseline Biomarker Levels (Exhibit Hall (Upper Concourse); Monitor 12) - Oct 10, 2022 - Abstract #ACAAI2022ACAAI_668;
P3
Conclusion Tezepelumab reduced levels of all key inflammatory biomarkers in patients with severe, uncontrolled asthma, with greater reductions in patients with higher baseline levels of the respective biomarker. These data further support the anti-inflammatory effects of tezepelumab in patients with severe asthma.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Efficacy Of Tezepelumab In Hispanic Or Latino Patients With Severe, Uncontrolled Asthma (Exhibit Hall (Upper Concourse); Monitor 12) - Oct 10, 2022 - Abstract #ACAAI2022ACAAI_667;
P2, P3
Among Hispanic/Latino patients, the AAER was 1.67 with placebo and 1.11 with tezepelumab (34% [95% CI: −7, 59] reduction versus placebo), and the annualized rate of asthma exacerbations requiring hospitalization was 0.12 with placebo and 0.00 with tezepelumab (100% [95% CI: not calculable, 100] reduction versus placebo) (Figure ). Conclusion Among patients of Hispanic or Latino ethnicity with severe, uncontrolled asthma, tezepelumab recipients had a lower rate of exacerbations over 52 weeks, including those requiring hospitalization.
- |||||||||| Efficacy Of Biologics In Patients With Severe Allergic Asthma, Overall And By Blood Eosinophil Count (M101-M102 (Main Concourse), Kentucky International Convention Center) - Oct 10, 2022 - Abstract #ACAAI2022ACAAI_594;
In the overall allergic population, data were available for tezepelumab, dupilumab and omalizumab only; the greatest AAER reduction was observed with tezepelumab...In patients with allergy and BEC less than 300 cells/μL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with mepolizumab, benralizumab or omalizumab...The efficacy of biologics varies considerably overall and by BEC. These differences can inform provider treatment decisions.
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