- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Journal: Is tezepelumab more than just an anti-eosinophil drug? (Pubmed Central) - Feb 3, 2022
Inhibiting TSLP-signalling with tezepelumab reduced the proportion of patients with AHR and decreased eosinophilic inflammation in BAL and airway tissue. No abstract available
- |||||||||| Journal: Antibodies to watch in 2022. (Pubmed Central) - Jan 27, 2022
Finally, our data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline of antibody therapeutics grew by over 30% in the past year. Of those in late-stage development, marketing applications for at least 22 may occur by the end of 2022.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen, Xolair (omalizumab) / Roche, Novartis
Clinical, Journal: Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy. (Pubmed Central) - Dec 30, 2021
P2
Of those in late-stage development, marketing applications for at least 22 may occur by the end of 2022. Treatment with tezepelumab reduced exacerbations, improved lung function and reduced T2 biomarkers versus placebo in patients with severe, uncontrolled asthma with or without perennial allergy, further supporting its efficacy in a broad population of patients with severe, uncontrolled asthma.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Clinical, P2 data, Journal: Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. (Pubmed Central) - Dec 29, 2021
P2
The improvements in asthma clinical outcomes observed in previous studies with tezepelumab are probably driven, at least in part, by reductions in eosinophilic airway inflammation, as shown here by reduced airway eosinophil counts regardless of baseline blood eosinophil count. Tezepelumab also reduced airway hyperresponsiveness to mannitol, indicating that TSLP blockade might have additional benefits in asthma beyond reducing type 2 airway inflammation.
- |||||||||| Tezspire (tezepelumab) / AstraZeneca, Amgen
Clinical, P3 data, PK/PD data, Journal: Pharmacokinetic and Pharmacodynamic Modeling of Tezepelumab to Guide Phase III Dose Selection for Patients with Severe Asthma. (Pubmed Central) - Dec 22, 2021
P2
Population PK simulations, exposure-response relationships and safety profiles of tezepelumab at doses up to 280 mg every 2 weeks suggested that no dose adjustment based on body weight or for adolescents was required. These results support the selection of 210 mg Q4W subcutaneously as the dose for phase III studies of tezepelumab in adults and adolescents with severe asthma.
- |||||||||| Xolair (omalizumab) / Roche, Novartis
EFFICACY OF BIOLOGIC THERAPIES IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA STRATIFIED BY BLOOD EOSINOPHIL COUNT (Hall B (1st Floor); Monitor 09) - Nov 2, 2021 - Abstract #ACAAI2021ACAAI_924;
In patients with BEC <300 cells/μL, efficacy was observed only with tezepelumab, whereas with benralizumab and dupilumab, AAER reduction was observed in one each of their two trials conducted...Omalizumab data in the ≥300 cells/μL panel are from patients with BEC ≥260 cells/μL...Patient numbers for the MUSCA/MENSA trials of mepolizumab in the 150–<300 cells/μL panel are for the overall population (breakdown by treatment group not given). CI, confidence interval; Ig, immunoglobulin; IU, international units; IV, intravenous; NR, not recorded; Q2W, every 2 weeks; Q4W, every 4 weeks; Q8W, every 8 weeks; SC, subcutaneous.
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
TEZEPELUMAB EFFICACY BY NUMBER OF SENSITIVITIES TO PERENNIAL AEROALLERGENS IN NAVIGATOR (217-219, Ernest N. Morial Convention Center) - Oct 23, 2021 - Abstract #ACAAI2021ACAAI_638;
P3
Data are from a negative binomial regression model with treatment, region, age group, history of exacerbations, subgroup and treatment-by-subgroup as covariates. Show full caption AAER, annualized asthma exacerbation rate; CI, confidence interval; Q4W, every 4 weeks.
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen, Xolair (omalizumab) / Roche, Novartis
TEZEPELUMAB EFFICACY ACCORDING TO US OMALIZUMAB ELIGIBILITY: RESULTS FROM THE NAVIGATOR PHASE 3 STUDY (217-219, Ernest N. Morial Convention Center) - Oct 23, 2021 - Abstract #ACAAI2021ACAAI_637;
P3
Data are from a negative binomial regression model with treatment, region, age group, exacerbation history, subgroup and treatment-by-subgroup as covariates. Show full caption AAER, annualized asthma exacerbation rate; CI, confidence interval; OMA, omalizumab; Q4W, every 4 weeks.
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
[VIRTUAL] EFFICACY OF TEZEPELUMAB IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA GROUPED BY BASELINE BMI IN THE NAVIGATOR STUDY () - Oct 13, 2021 - Abstract #CHEST2021CHEST_1042;
P3
Tezepelumab reduced exacerbations, including those that required hospitalization or an ED visit, compared with placebo in patients with severe, uncontrolled asthma, across the BMI subgroups assessed. CLINICAL IMPLICATIONS: Consistent with observations in the phase 2b PATHWAY study, this analysis demonstrates the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma, including those with a BMI ≥ 30 kg/m2, which may be associated with a non-eosinophilic asthma phenotype.
- |||||||||| Xolair (omalizumab) / Roche, Novartis
Review, Journal: Biologics for the Treatments of Allergic Conditions: Severe Asthma. (Pubmed Central) - Oct 6, 2021
Some practical aspects including optimal treatment duration, the possibility of a dose treatment modulation, the place and relevance of ICS in best responders are still under debate. Long-term safety, especially when interacting with innate immunity needs to be further investigated.
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
Review, Journal: Tezepelumab as an Emerging Therapeutic Option for the Treatment of Severe Asthma: Evidence to Date. (Pubmed Central) - Oct 2, 2021
Proof of concept study and phase IIb studies demonstrated reduced asthma exacerbations, improvement in quality of life, less decline in FEV and decrease in biochemical inflammatory markers in comparison to placebo. It is presently undergoing three phase III studies and an additional phase II study.
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
Clinical, Review, Journal: Monoclonal Antibodies Targeting Alarmins: A New Perspective for Biological Therapies of Severe Asthma. (Pubmed Central) - Sep 29, 2021
Within this context, the fully human anti-TSLP monoclonal antibody tezepelumab has been evaluated in very promising randomized clinical trials. Tezepelumab and other anti-alarmins are thus likely to become, in the near future, valuable therapeutic options for the biological treatment of uncontrolled severe asthma.
- |||||||||| Xolair (omalizumab) / Roche, Novartis
Review, Journal: The Impact of Monoclonal Antibodies on Airway Smooth Muscle Contractility in Asthma: A Systematic Review. (Pubmed Central) - Sep 29, 2021
Conversely, mepolizumab and benralizumab have prevalently indirect impacts against AHR by targeting eosinophils and other immunomodulatory effector cells promoting inflammatory processes. AHR has been suggested as the main treatable trait towards precision medicine in patients suffering from eosinophilic asthma, therefore, well-designed head-to-head trials are needed to compare the efficacy of those mAbs that directly target ASM contractility specifically against the AHR in severe asthma, namely omalizumab, dupilumab, and tezepelumab.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Trial completion date, Trial primary completion date: DIRECTION: Study to Evaluate Tezepelumab in Adults With Severe Uncontrolled Asthma (clinicaltrials.gov) - Sep 23, 2021
P3, N=396, Recruiting,
AHR has been suggested as the main treatable trait towards precision medicine in patients suffering from eosinophilic asthma, therefore, well-designed head-to-head trials are needed to compare the efficacy of those mAbs that directly target ASM contractility specifically against the AHR in severe asthma, namely omalizumab, dupilumab, and tezepelumab. Trial completion date: May 2025 --> Aug 2024 | Trial primary completion date: May 2025 --> Aug 2024
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Trial completion date, Trial primary completion date: TRAILHEAD: Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma (clinicaltrials.gov) - Sep 23, 2021
P1, N=14, Recruiting,
Trial completion date: May 2025 --> Aug 2024 | Trial primary completion date: May 2025 --> Aug 2024 Trial completion date: Dec 2021 --> Jun 2022 | Trial primary completion date: Dec 2021 --> Jun 2022
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen, Xolair (omalizumab) / Roche, Novartis, Fasenra (benralizumab) / AstraZeneca
Review, Journal: Molecular Targets for Biological Therapies of Severe Asthma: Focus on Benralizumab and Tezepelumab. (Pubmed Central) - Aug 28, 2021
In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor, and IL-4 and IL-13 can be targeted by dupilumab...These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, which are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. The aim of the study is to review the immunopathology and treatment efficacy for severe asthma and focused on new biological agents with benralizumab (anti-IL-5) and tezepelumab (anti-TSLP).
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
Clinical, P3 data, Journal: DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma. (Pubmed Central) - Aug 22, 2021
P3
DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma.
- |||||||||| Tezspire (tezepelumab-ekko) / AstraZeneca, Amgen
Trial completion date, Trial primary completion date: TRAILHEAD: Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma (clinicaltrials.gov) - Aug 18, 2021
P1, N=14, Recruiting,
This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma. Trial completion date: Sep 2021 --> Dec 2021 | Trial primary completion date: Sep 2021 --> Dec 2021
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
Clinical, P1 data, PK/PD data, Journal: A Phase 1, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Subcutaneous Tezepelumab in Healthy Japanese Men. (Pubmed Central) - Aug 11, 2021
Single-dose, subcutaneous administration of tezepelumab 35 to 280 mg resulted in an acceptable safety profile with linear pharmacokinetics in healthy Japanese men. No clear differences in tezepelumab safety and pharmacokinetics between Japanese and non-Japanese populations were identified.
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
Clinical, P3 data, Journal: SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma. (Pubmed Central) - Aug 7, 2021
P2, P3
SOURCE is evaluating the OCS-sparing potential of tezepelumab in patients with OCS-dependent asthma. SOURCE also aims to demonstrate that treatment with tezepelumab in patients with severe asthma is associated with reductions in exacerbation rates and improvements in lung function, asthma control and health-related quality of life, while reducing OCS dose.
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
Clinical, P3 data, Journal: NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. (Pubmed Central) - Aug 7, 2021
P2, P3
The target sample size for NAVIGATOR (N = 1060) was achieved, and it is the largest clinical study of tezepelumab in severe, uncontrolled asthma to date. NAVIGATOR aims to further investigate the effect of tezepelumab on exacerbations and build on observations from the phase 2b PATHWAY study, and to demonstrate further the potential of tezepelumab to provide patients with severe, uncontrolled asthma with improvements in lung function, asthma control and health-related quality of life.
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
Journal: Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option? (Pubmed Central) - Aug 7, 2021
P2, P3
In addition, an ongoing phase 2 bronchoscopy study, CASCADE (NCT03688074), aims to evaluate the effect of tezepelumab on airway inflammation and airway remodelling in patients across the spectrum of type 2 airway inflammation. Here, we summarize the unmet therapeutic need in severe asthma and the current treatment landscape, discuss the rationale for targeting TSLP in severe asthma therapy and describe the current development status of tezepelumab.
- |||||||||| tezepelumab (AMG 157) / AstraZeneca, Amgen
[VIRTUAL] Effect of tezepelumab on exacerbation-related oral corticosteroid use in NAVIGATOR (Channel 2) - Jul 29, 2021 - Abstract #ERS2021ERS_2437;
P3
The median (interquartile range) total number of days with exacerbation-related OCS use per patient was lower in the tezepelumab group (9 [5–16]) than the placebo group (14 [7–29]). Conclusion Patients with severe, uncontrolled asthma treated with tezepelumab had fewer days of OCS use for exacerbations than those who received placebo.
- |||||||||| Dupixent (dupilumab) / Sanofi, Regeneron
[VIRTUAL] A computational model suggested potential therapies for dupilumab poor responders in atopic dermatitis () - Jul 8, 2021 - Abstract #ESDR2021ESDR_132;
The model will serve as a computational platform for model-informed drug development for precision medicine, as it allows to evaluate the validity of potential drug targets, including combinations of multiple targets, in stratified patients. Similar mathematical models and simulation can be also applicable for other diseases and therapies when there are reported clinical efficacies of multiple drugs.
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